Formation of condensed 1 H-pyrrol-2-ylphosphonates and 1,2-dihydropyridin- 2-ylphosphonates via Kabachnik-fields reaction of acetylenic aldehydes and subsequent 5-exo-dig or 6-endo-dig cyclizations

Article

pubs.acs.org/joc

Formation of Condensed 1H‑Pyrrol-2-ylphosphonates and 1,2-

Dihydropyridin-2-ylphosphonates via Kabachnik−Fields Reaction of

Acetylenic Aldehydes and Subsequent 5-exo-dig or 6-endo-dig

Cyclizations

̌

Rita Buksnaitiene, Aurelija Urbanaite, and Inga Cikotiene*

̌

̇

Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania

S

* Supporting Information

ABSTRACT: Kabachnik−Fields reactions of various carbocyclic or

heterocyclic acetylenic aldehydes together with subsequent Lewis acid

catalyzed cyclizations have been studied. It was found that 5-exo-dig

versus 6-endo-dig cyclization mode strongly depends on the structure of

starting materials. Thus, nonaromatic acetylenic α-anilinomethylphosph-

onates underwent gold(III)-catalyzed or iodine-mediated 5-exo-dig

cyclization to 1H-pyrrol-2-ylphosphonates. In contrast, electron-with-

drawing heteroaromatic substrates formed 1,2-dihydropyridin-2-yl-

phosphonate ring containing materials via an exclusive 6-endo-dig ring-

closure process. The dual mode of cyclization is possible only for α-

amino (2-alkynylphenyl)methylphosphonates containing a benzene ring .

Scheme 1. Results of Ding et al. Published in 2007^5a

INTRODUCTION

■

Both heterocyclic pyrrole¹and 1,2-dihydropyridine²ring

systems are important skeletons in natural and synthetic

bioactive products. Also, it is well-known that α-amino-

phosphonates attract attention as analogues of α-amino acids

possessing a variety of important biological activities.³

Combination of pyrrole and dihydropyridine rings together

with the phosphonate functionality would represent a class of

cyclic α-aminophosphonates with promising biological applica-

tions.⁴

In 2007 several manuscripts about the formation of dialkyl

on the structure of starting material, due to diﬀerent electronic

1H-pyrrol-2-ylphosphonates and 1,2-dihydropyridin-2-yl-

densities on triple bond carbons. For the evaluation of this idea

phosphonates (Figure 1) via Lewis acid catalyzed cyclizations

we chose a variety of carbocyclic and heterocyclic acetylenic α-

anilinomethylphosphonates and tested their cyclization reac-

tions.

In this work we present the results of our investigations.

RESULTS AND DISCUSSION

The corresponding 2-alkynylcyclopent-1-enecarbaldehydes 1,

2-alkynylcyclohex-1-enecarbaldehydes 2, 2-alkynylbenzalde-

■

Figure 1. Structures of 1H-pyrrol-2-ylphosphonate and 1,2-dihydro-

pyridin-2-ylphosphonate.

hydes 3, 2-alkynylindole-3-carbaldehydes 4, 2-alkynylpyridine-

3-carbaldehydes 5, and 2-alkynylquinoline-3-carbaldehydes 6

(Figure 2) were reacted by the classical Sonogashira coupling⁶

of α-amino (2-alkynylphenyl)methylphosphonates were pub-

between 2-bromocyclopent-1-enecarbaldehyde,⁷2-bromocyclo-

hex-1-enecarbaldehyde,⁸and commercially available 2-bromo-

benzaldehyde, 2-bromo-1H-indole-3-carbaldehyde, 2-bromo-

lished by Ding et al.⁵The authors proved that, in principle,

both cyclization modes are possible and showed that 5-exo-dig

versus 6-endo-dig cyclization regioselectivity could be simply

switched by changing the catalyst (Scheme 1).^5a

However, we envisioned that the cyclization regioselectivity

of acetylenic α-anilinomethylphosphonates could also depend

Received: May 9, 2014

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Figure 2. Starting acetylenic aldehydes. 1a: R = Ph; 1b: R = 4-MeC₆H₄; 1c: R = 4-EtC₆H₄; 1d: R = Bu; 1e: R = C₅H₁₁; 1f: R = c-Pr; 1g: R = TMS.

2a: R = Ph; 2b: R = 4-MeC₆H₄; 2c: R = Pr; 2d: R = Bu; 2e: R = C₅H₁₁; 2f: R = c-Pr. 3a: R = Ph; 3b: R = TMS. 4a: R = Ph; 4b: R = Bu; 4c: R = c-Pr.

5a: R = Ph; 5b: R = Pr; 5c: R = c-Pr; 5d: R = H; 5e: R = CH₂OTHP. 6a: R = Ph; 6b: R = Bu; 6c: R = Pr; 6d: c-Pr.

pyridine-5-carbaldehyde, 2-chloroquinoline-3-carbaldehyde,

and terminal acetylenes. The reactions proceeded smoothly in

THF at room temperature under argon atmosphere in the

presence of 4 mol % PdCl₂(PPh₃)₂and 2 mol % CuI and 2

equiv of triethylamine. Then with the synthesized acetylenic

aldehydes in hand, we utilized the Kabachnik−Fields reaction⁹

between starting materials, anilines, and dimethylphosphite and

screened synthetic approaches for the preparation of various

phopshonated pyrrole or dihydropyridine core contacting

compounds.

iodide was totally ineﬀective for the cyclization and the starting

material 7a was isolated after the workup of reaction mixture

(Table 1, entry 1). When PdCl₂was utilized as a catalyst in

Table 1. Screening of the Cyclization Reaction of Dimethyl

(Phenylamino)[2-(phenylethynyl)cyclopent-1-

enyl]methylphosphonate 7a

Synthetic Utility of Carbocyclic Acetylenic Aldehydes

for the Preparation of Materials Having Pyrrole-1-

phosphonate Functionalities. The Kabachnik−Fields re-

action is a three-component process forming α-amino-

phosphonates from carbonyl compounds, amines, and dialkyl

phosphonates. Despite a variety of method variations,¹⁰the

presence of a Lewis acid in solution or in solvent-free

conditions is usually required. After a brief search of optimal

reaction conditions, we found that 1 equiv of BF₃·OEt₂in

dichloromethane at room temperature gave the best results and

did not cause polymerization of chemically unstable aldehydes

1 and 2. Thus, when carbocyclic aldehydes 1−3 were stirred

with anilines and dimethylphosphite in dichloromethane in the

presence of 1 equiv of BF₃·OEt₂at room temperature, the

corresponding acetylenic α-anilinomethylphosphonates 7−9

were formed in moderate or good yields (Scheme 2).

yield

recovered

entry

reaction conditions

time, h 10a, %

7a, %

1

2

3

4

CuI (10 mol %), CHCl₃, rt

PdCl₂(10 mol %), CHCl₃, rt

PdCl₂(10 mol %), CH₃CN, rt

48

95

79

78

42

48

10

11

30

PdCl₂(PPh₃)₂(10 mol %), CHCl₃,

rt

5

6

7

8

9

AgNO₃(10 mol %), CHCl₃, rt

CF₃CO₂Ag (10 mol %), CHCl₃, rt

CF₃SO₃Ag (10 mol %), CHCl₃, rt

AuBr₃(5 mol %), CHCl₃, rt

48

20

8

36

74

68

45

13

45

70

99

AuBr₃(10 mol %), CHCl₃, rt

10 AuBr₃(10 mol %),

KOtBu (1 equiv), CHCl₃, rt

0.5

Scheme 2. Kabachnik−Fields Reaction of Carbocyclic

a

Acetylenic Aldehydes 1−3

chloroform or acetonitrile solutions, poor conversion of 7a was

reached and compound 10a was isolated in 10% and 11% yields

(Table 1, entries 2, 3). PdCl₂(PPh₃)₂as well as various silver

salts (AgNO₃, CF₃CO₂Ag, and CF₃SO₃Ag) also were not very

eﬀective, and after insuﬃcient conversion of the starting

material, pyrrole derivative 10a was isolated in 20%, 8%, and

13% yields, respectively (Table 1, entries 4−7). After treatment

of the starting alkyne by 5 mol % gold(III) bromide in

chloroform at room temperature, 50% conversion of 7a was

reached in 48 h, aﬀording 45% of ﬁnal 10a (Table 1, entry 8).

Increasing the amount of AuBr₃to 10 mol % resulted in full

conversion of the starting material in 48 h, and 10a was

obtained in 70% yield (Table 1, entry 9). To our delight,

addition of 1 equiv of potassium tert-butanoate speeded up the

reaction, and high-yielding formation of 10a was achieved after

30 min of stirring at room temperature (Table 1, entry 10).¹¹

In contrast, aromatic dimethyl (phenylamino)(2-

phenylethynylphenyl)methylphosphonate 9a is able to undergo

either 5-exo-dig or 6-endo-dig cyclizations. This dual reactivity of

dialkyl (arylamino)(2-alkynylphenyl)methylphosphonates was

described by Ding et al. in 2007.^5aThe authors showed that on

one hand, palladium chloride in acetonitrile initiated

regioselective 5-exo-dig cyclization followed by [1,5]-H shift

a

Reagents and conditions: (i) ArNH₂(1 equiv), dimethylphosphite

(1.1 equiv), BF₃·OEt₂(1 equiv), DCM, rt, 12−24 h. Structures of 7−9

are depicted in Tables 4 and 5.

Next, the cyclization reaction of dimethyl (phenylamino)[2-

(phenylethynyl)cyclopent-1-enyl]methylphosphonate 7a was

chosen for optimization of conditions. The aromatic substrate

dimethyl (phenylamino)[2-(phenylethynyl)phenyl]-

methylphosphonate 9a was used as a model substrate for

comparison. The data obtained are depicted in Tables 1 and 2.

First of all, it should be noted that in all successful cases the

starting material 7a underwent regioselective 5-exo-dig

cyclization followed by aromatization and formation of the

tetrahydrocyclopenta[c]pyrrole core. No 6-endo-dig cyclization

product was observed by TLC and NMR monitoring of crude

mixtures. Screening of Lewis acids revealed that copper(I)

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Table 2. Data of 5-exo-dig or 6-endo-dig Cyclization Reactions of Dimethyl (phenylamino)(2-

phenylethynylphenyl)methylphosphonate 9a

entry

reaction conditions

time, h

product

yield, %

1

2

3

AuBr₃(10 mol %), KO^tBu (1 equiv), CHCl₃, rt

24

32

72

11a

12a

53

72

86

PdCl₂(5 mol %), CH₃CN, 60−70 °C

CF₃SO₃Ag (5 mol %), CH₃CN, 60−70 °C

Table 3. Screening of the Iodine-Mediated Cyclization Reaction of Dimethyl (Phenylamino)[2-(phenylethynyl)cyclopent-1-

enyl]methylphosphonate 7a

entry

reaction conditions

I₂(4 equiv), CHCl₃, rt

time, h

yield 13a, %

recovered 7a, %

1

12

1

12

11

48

24

30

28

2

I₂(1 equiv), KO^tBu (1 equiv), CHCl₃, 0 °C → rt

I₂(1 equiv), K₂CO₃(1 equiv), CHCl₃, 0 °C → rt

I₂(1 equiv), K₂CO₃(1 equiv), acetone, rt

I₂(1 equiv), K₂CO₃(1 equiv), CH₃CN, rt

I₂(1 equiv), K₂CO₃(1 equiv), CH₃NO₂, rt

I₂(1 equiv), K₂CO₃(1 equiv), CH₃OH, rt

I₂(1 equiv), K₂CO₃(1 equiv), C₆H₅CH₃, rt

I₂(1 equiv), NaHCO₃(1 equiv), CHCl₃, 0 °C → rt

I₂(1 equiv), K₃PO₄(1 equiv), CHCl₃, 0 °C → rt

Py₂IBF₄(1 equiv), CHCl₃, rt

3

4

24

32

43

85

5

6

7

8

9

65

67

10

11

12

49

I₂(1 equiv), PhI(OAc)₂(2 equiv), CHCl₃, 0 °C → rt

89

to the corresponding 2,3-disubstituted-2H-isoindol-1-ylphosph-

onates. On the other hand, silver triﬂate catalyzed 6-endo-dig

cyclization reaction to 2,3-disubstituted-1,2-dihydroisoquinolin-

1-ylphosphonates. Indeed benzene derivative 9a was able to

undergo both cyclization processes as it was reported by Ding

et al. (Table 2, entries 2 and 3).^5aThese methods required

prolonged heating in acetonitrile. It should be noted that

gold(III) bromide together with 1 equiv of potassium tert-

butanoate in chloroform also initiated 5-exo-dig cyclization

process at room temperature and ﬁnal 11a was formed in 53%

yield (Table 2, entry 1).

Thus, gold(III) bromide was able to initiate exclusive 5-exo-

dig cyclization reactions of carbocyclic acetylenic α-anilinome-

thylphosphonates. With these promising results in hands and

having in mind literature facts that various intramolecular

transformations of functionally substituted alkynes can be

carried out with either gold catalysts or iodine electrophiles to

access the same core unit,¹²we decided to evaluate the

usefulness of iodine electrophiles in this cyclization. Indeed, we

found, that molecular iodine was able to mediate the cyclization

process of (phenylamino)[2-(phenylethynyl)cyclopent-1-enyl]-

methylphosphonate 7a. In all cases dimethyl 3-benzoyl-2-

phenyl-2,4,5,6-tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate

13a bearing a carbonyl functionality instead of a methylene

group was formed. Full conversion of the starting material 7a

was reached in 12 h. However, use of an excess of molecular

iodine (Table 3, entry 1), as well as 1 equiv of molecular iodine

together with 1 equiv of potassium tert-butanoate at 0 °C

temperature (Table 3, entry 2) facilitated the formation of tars,

and only minor quantities of 13a were isolated. While use of

potassium carbonate (Table 3, entry 3), sodium bicarbonate

(Table 3, entry 9), and potassium phosphate (Table 3, entry

10) in chloroform at 0 °C temperature improved yield of the

cyclization product, potassium carbonate in acetone (Table 3,

entry 4), acetonitrile (Table 3, entry 5), and nitromethane

(Table 3, entry 6) led to insuﬃcient conversion of the starting

alkyne. It also should be noted that combination of equivalent

amounts of the starting material, molecular iodine, and

potassium carbonate in methanol (Table 3, entry 7) or toluene

(Table 3, entry 8) did not give the desired product, and 85% of

starting alkyne was recovered or full decomposition of it was

observed, respectively. The Barluenga reagent¹³was not able to

mediate the cyclization process, and 49% of the starting

material was recovered (Table 3, entry 11). Then, the

electrophilicity of iodine was improved by adding hypervalent

iodine oxidant.¹⁴To our delight, the combination of 1 equiv of

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Table 4. Data on the Synthesis of Polysubstituted Pyrrol-1-ylphosphonates via Gold(III) Bromide Mediated Cyclization

molecular iodine together with 2 equiv of phenyliodine

diacetate in chloroform at 0 °C temperature resulted in full

conversion of the starting alkyne and smooth formation of 13a

in 89% yield (Table 3, entry 12).

Optimized reaction conditions (Table 1, entry 10 and Table

3, entry 12) were applied for the synthesis of polysubstituted

pyrrol-1-ylphosphonates 10 and 13−18. The results are

summarized in Tables 4 and 5. As is seen from Table 4, both

starting substrates 7 and 8 having cyclopentene and cyclo-

hexene rings underwent smooth and high-yielding formation of

pyrrol-1-ylphosphonates 10 and 14 via gold(III) bromide

catalyzed process (entries 1−32).

Molecular iodine mediated cyclizations proceeded smoothly

for substrates 7a−h,j,s (Table 5, entries 1−10), 8a,b,o,p (Table

5, entries 13−15), and 9b,c (Table 5, entries 18, 19) having

arylethynyl or ethynyl functionality. The corresponding ketones

13a−g,h,j, 16a,b,o, 18b and aldehydes 13s and 18c were

isolated in moderate or good yields. However, derivatives 7i, 7o

(Table 5, entries 11, 12) and 8k, 8l (Table 5, entries 16, 17)

bearing an alkylethynyl substituent cyclized into pyrrol-1-

ylphosphonates bearing 1-iodoalkenyl substituents. The latter

four compounds were isolated as mixtures of E and Z isomers.

The plausible mechanism of the iodine-mediated cyclization

is depicted in Scheme 3. We believe that at the ﬁrst step,

molecular iodine is converted to 2 equiv of acetyl hypoiodite

during oxidation by phenyliodine diacetate.¹⁴Thus, an

electrophilic I⁺is generated in an eﬃcient and atom-economic

way. The formation of byproduct iodobenzene was proved by

NMR and MS methods. Next, after direct iodonium activation

(intermediate I) of the triple bond of the starting substrate, the

intramolecular 5-exo-dig nucleophilic attack of the neighboring

arylamino group takes place, leading to intermediate II, and loss

of a proton gives neutral intermediate III. Next, the second

electrophilic iodine attack of the exocyclic double bond occurs,

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Table 5. Data on the Synthesis of Polysubstituted Pyrrol-1-ylphosphonates 13 and 15−18 via Iodine-Mediated Cyclization

thus aﬀording intermediate IV. Abstraction of a proton leads to

aromatization of the pyrrole ring and formation of di-iodo

intermediates VI and VII. However, when starting compound

has a cyclopropyl functionality next to the triple bond, during

the iodination-aromatization processes cleavage of the cyclo-

propane ring occurs, giving di-iodo derivatives 15 and 17.

Intermediate VI can undergo nucleophilic displacement

reaction with water, forming carbonyl group bearing products

13, 16, 18. In contrast, intermediate VII, bearing a CH₂R¹

group, undergoes base-mediated elimination reaction to

compounds 15 and 17.

The role of water in formation of products 13, 16, and 18

was proved by addition of ¹⁸O-labeled water to the reaction

mixture. Stirring of 7a with 1 equiv of molecular iodine and 2

equiv of phenyliodine diacetate in chloroform in the presence

of 3 equiv of ¹⁸O-labeled water resulted in smooth formation of

13a-¹⁸O in 86% yield. The HRMS spectrum of 13a-¹⁸O

conﬁrmed absolute incorporation of ¹⁸O in ﬁnal ketone.

Moreover, an observed δ 0.04 ppm (4 Hz) upﬁeld chemical

shift was found for ketone carbonyl carbon in ¹³C NMR

spectrum of 13a-¹⁸O, thus conﬁrming position of ¹⁸O.¹⁵

Kabachnik−Fields Reactions of Heterocyclic Alde-

hydes and Cyclization Reaction of Obtained Adducts.

After exploring the reactivity of carbocyclic acetylenic aldehydes

and their Kabachnik−Fields adducts, we turned our attention

to heterocyclic substrates. Electron-rich 2-(alkynyl)-1-benzyl-

1H-indole-3-carbaldehydes (4) reacted under the Kabachnik−

Fields reaction condition and formed the corresponding

adducts 19 in moderate yields (Scheme 4).

Unfortunately, the presence of an electron-rich indole ring

deactivated isolated compounds 19 toward the cyclization

reaction. No changes of the starting materials 19 were observed

by TLC or NMR monitoring during prolonged stirring or

reﬂuxing of compounds 19 in dichloroethane, in the presence

of gold(III) bromide, palladium(II) chloride, silver(I) triﬂate, or

I₂/DIB.

However, when we tried to perform the Kabachnik−Fields

reaction of electron-deﬃcient pyridine or quinoline substrates 5

and 6, we surprisingly found that these reactions were not so

E

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Scheme 3. Plausible Mechanism of the Iodine-Mediated Cyclization of Acetylenic α-Anilinomethylphosphonates

silver(I) triﬂate) in DCE at room temperature gave the best

results. Thus, the corresponding dimethyl 6-aryl-5,6-dihydro-

1,6-naphthyridin-5-ylphosphonates 20 and dimethyl 2-aryl-1,2-

dihydrobenzo[b][1,6]naphthyridin-1-ylphosphonates 21 were

isolated in good yields after stirring of reaction mixtures at

room temperature for 2−4 h. (Scheme 5, Table 6). We believe

that after formation of intermediate imines VIII, tandem

dimethylphosphite addition−6-endo-dig cyclization reactions

took place. An immediate nucleophilic attack of imine group

is facilitated by decreased electron density on the triple bond of

intermediates VIII.

The mechanism presented in Scheme 5 was supported by

isolation of intermediate 22 (Figure 3) after the reaction

between starting 2-phenylethynylquinolin-3-carbaldehyde 6a

and 4-methoxyaniline in chloroform in the presence of 3Å MS.

Then, after stirring of compound 22 with dimethylphosphite in

DCE in the presence of 10 mol % CuI, smooth 6-endo-dig

cyclization process proceeded, and ﬁnal product 21a was

isolated in 64% yield.

Scheme 4. Kabachnik−Fields Reaction of 2-Alkynylindole-3-

a

carbaldehydes 4

a

Reagents and conditions: (i) aniline (1 equiv), dimethylphosphite

(1.1 equiv), BF₃·OEt₂(1 equiv), DCM, rt, 24 h. 19a: R = Ph, Ar = Ph;

19b: R = Bu, Ar = 4-CH₃OC₆H₄-; 19c: R = cPr, Ar = Ph.

straightforward and BF₃·OEt₂did not mediate an exclusive

formation of the Kabachnik−Fields adducts. Reactions

proceeded slowly, and after NMR analysis of crude mixtures

we found that after 12−24 h there were products of 6-endo-dig

cyclization process 20 or 21 together with the corresponding

imines VIII. After a brief searching of the most suitable reaction

conditions for the full conversion to cyclized 20 and 21, we

came to conclusion that 10 mol % copper iodide (in

comparison to gold(III) bromide, palladium(II) chloride, or

Moreover, we succeeded in synthesizing the Kabachnik−

Fields reaction product 23 during reaction between starting

aldehyde 6c with 4-methoxyaniline and dimethylphosphite in

dichloromethane in the presence of 10 mol % gold(III)

a

Scheme 5. Three-Component Reaction between Electron-Deﬃcient Aldehydes 5 and 6, Anilines, and Dimethylphosphite

a

Reagents and conditions: (i) aniline (1 equiv), dimethylphosphite (1.1 equiv), CuI (10 mol %), DCM, rt, 2−4 h.

F

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Table 6. Data on the Synthesis of Dimethyl 6-Aryl-5,6-

dihydro-1,6-naphthyridin-5-ylphosphonates 20 and

Dimethyl 2-Aryl-1,2-dihydrobenzo[b][1,6]naphthyridin-1-

a

ylphosphonates 21

Figure 3. (E)-4-Methoxy-N-{[2-(phenylethynyl)quinolin-3-yl]-

methylene}aniline 22.

bromide (Scheme 6). Together with compound 23, the

corresponding cyclized 1,2-dihydrobenzo[b][1,6]naphthyridin-

1-ylphosphonate 21e was formed. After isolation and

puriﬁcation of 23, we tested its reactivity toward various

Lewis acids (AuBr₃, AgOTf, CuI, I₂in neutral and basic media)

and found that in all cases slow formation of 6-endo-dig

cyclization product 21e with incomplete conversion of

compound 23 took place. Thus, it was showed that reaction

of electron-withdrawing heterocyclic acetylenic aldehydes with

anilines and dimethylphosphite likely does not proceed via the

Kabachnik−Fields reaction adducts, but mainly via imines VIII.

The triple bond of intermediates VIII is activated by

neighboring electron-withdrawing pyridine and quinoline

rings, and therefore smooth tandem dimethylphosphite

attack−6-endo-dig cyclization reactions take place.

CONSLUSION

■

Kabachnik−Fields reactions between 2-alkynylcyclopent-1-

enecarbaldehydes, 2-alkynylcyclohex-1-enecarbaldehydes, 2-al-

kynylbenzaldehydes, 2-alkynylindole-3-carbaldehydes, 2-alky-

nylpyridine-3-carbaldehydes, and 2-alkynylquinoline-3-carbal-

dehydes have been studied. It has been found that substrates

having carbocyclic and electron-rich indole ring successfully

undergo BF₃·OEt₂-mediated reactions with anilines and

dimethylphoshphite, yielding the corresponding Kabachnik−

Fields adducts. In contrast, electron-deﬃcient 2-alkynylpyr-

idine-3-carbaldehydes and 2-alkynylquinoline-3-carbaldehydes

undergo smooth tandem imine formation−6-endo-dig cycliza-

tion processes forming the corresponding dimethyl 6-aryl-5,6-

dihydro-1,6-naphthyridin-5-ylphosphonates and dimethyl 2-

aryl-1,2-dihydrobenzo[b][1,6]naphthyridin-1-ylphosphonates.

A variety of Lewis acids have been investigated for the

cyclization processes of all isolated acetylenic α-anilinomethyl-

phosphonates (Scheme 7).

An important conclusion of this study is that 5-exo-dig and 6-

endo-dig cyclization processes can be switched by using a

diﬀerent catalyst only in the case of starting benzene

derivatives. However, while on one hand substrates having

nonaromatic cyclopentene or cyclohexene rings undergo

exclusive 5-exo-dig cyclization processes to form polysubstituted

pyrrole derivatives, on the other hand, substrates having

electron-deﬃcient pyridine or quinoline rings always undergo

6-endo-dig cyclization processes. Finally, substrates bearing an

electron-donating indole ring are totally unreactive toward

Lewis acid catalyzed cyclization processes.

Additionally, during this study, a new iodine-mediated

synthetic method of aroyl- or formyl-substituted pyrrole-1-

phosphonates has been developed.

EXPERIMENTAL SECTION

■

1

a

General Information. IR spectra were run in KBr discs. H and

Reactions between starting materials, the corresponding aniline (1

¹³C NMR spectra were recorded at either 300 or 400 MHz in

equiv), and dimethylphosphite (1.1 equiv) were carried out in DCM at

rt in the presence of CuI (10 mol %) for 2−4 h.

chloroform-d or dimethylsulfoxide-d₆, using the residual solvent signal

G

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a

Scheme 6

a

Reagents and conditions: (i) 4-methoxyaniline (1 equiv), dimethylphosphite (1.1 equiv), AuBr₃(10 mol %), DCM, rt, 3 h. (ii) AuBr₃(10 mol %),

DCM, rt 24 h. (iii) AgOTf (10 mol %), DCM, rt 24 h. (iv) CuI (10 mol %), DCM, rt 24 h. (v) I₂(1 equiv), K₃PO₄(1 equiv), CHCl₃, 0 °C → rt, 10

h.

quenched with aqueous sodium bicarbonate. The organic layer was

separated, washed with water (2 × 20 mL), and dried over anhydrous

Na₂SO₄. After the evaporation of solvent under reduced pressure, the

residue was puriﬁed by ﬂash column chromatography eluting with

hexane−ethyl acetate mixtures.

Scheme 7. Dependence of the Cyclization Mode on the

Structures of the Starting Acetylenic α-

Anilinomethylphosphonates

Dimethyl (Phenylamino)(2-(phenylethynyl)cyclopent-1-

enyl)methylphosphonate (7a). Yellow solid, mp114−115 °C.

Yield 0.48 g, 63%. IR (KBr): υ_max3488 (NH), 2200 (CC) cm⁻¹.

¹H NMR (300 MHz, CDCl₃): δ 1.77−1.99 (2H, m, CH₂CH₂CH₂),

2.37−2.50 (1H, m, CH₂CH₂CH₂), 2.56−2.68 (3H, m, CH₂CH₂CH₂),

3

3.80 (3H, d, J_H,P= 10.8 Hz, OCH₃), 3.85 (3H, d, J_H,P= 10.8 Hz,

OCH₃), 5.02 (1H, d, ³J_H,P= 24.9 Hz, CH), 6.70−6.78 (3H, m, ArH),

7.15−7.20 (2H, m, ArH), 7.33−7.37 (3H, m, ArH), 7.48−7.51 (2H,

m, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 22.2 (CH₂), 32.6

5

1

(CH₂), 36.7 (d, J_C,P= 2.1 Hz, CH₂), 51.3 (d, J_C,P= 153.6 Hz, CH),

2

53.6 (d, J_C,P= 7.2 Hz, OCH₃), 53.8 (d, J_C,P= 6.6 Hz, OCH₃), 84.9

4

5

(d, J_C,P= 5.1 Hz, C-sp), 96.0 (d, J_C,P= 2.4 Hz, C-sp), 113.9 (ArC),

118.9 (ArC), 123.1 (ArC), 124.2 (d, J_C,P= 12.9 Hz, C-sp²), 128.3

3

2

(ArC), 128.4 (ArC), 129.2 (ArC), 131.3 (ArC), 144.9 (d, J_C,P= 4.7

Hz, C-sp²), 145.9 (d, ³J_C,P= 15.3 Hz, ArC) ppm. HRMS (ESI): MNa⁺,

found 404.1830. C₂₂H₂₄NNaO₃P requires 404.1836.

Dimethyl (4-Methoxyphenylamino)(2-(phenylethynyl)-

cyclopent-1-enyl)methylphosphonate (7b). Yellow solid, mp

121−122 °C. Yield 0.44 g, 54%. IR (KBr): υ_max3436 (NH), 2200

1

(CC) cm⁻¹. H NMR (300 MHz, CDCl₃): δ 1.76−1.98 (2H, m,

CH₂CH₂CH₂), 2.38−2.49 (1H, m, CH₂CH₂CH₂), 2.56−2.68 (3H, m,

CH₂CH₂CH₂), 3.80 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.85 (3H, d, ³J_H,P

= 10.8 Hz, OCH₃), 4.94 (1H, d, ³J_H,P= 24.6 Hz, CH), 6.67−6.77 (4H,

as internal standard. Signal multiplicity is denoted as follows: s

(singlet), d (doublet), t (triplet), q (quartet), quint (quintet), m

(multiplet). Unambiguous assignment of signals was made using a

combination of NMR experiments, including COSY, HSQC, and

HMBC. High resolution mass spectra were recorded on a Dual-ESI Q-

TOF 6520 mass spectrometer by electrospray ionization. All reactions

and purity of the synthesized compounds were monitored by TLC

using silica gel 60 F254 aluminum plates. Visualization was

accomplished by UV light and by treating the plates with vanillin

stain followed by heating.

m, ArH), 7.32−7.36 (3H, m, ArH), 7.45−7.50 (2H, m, ArH) ppm. ¹³C

5

NMR (75 MHz, CDCl₃): δ 22.2 (CH₂), 32.6 (CH₂), 36.7 (d, J_C,P

=

2.0 Hz, CH₂), 52.2 (d, ¹J_C,P= 153.8 Hz, CH), 53.5 (d, J_C,P= 7.0 Hz,

2

OCH₃), 53.8 (d, ²J_C,P= 6.6 Hz, OCH₃), 55.5 (OCH₃), 85.0 (d, ⁴J_C,P

=

5

6.9 Hz, C-sp), 95.9 (d, J_C,P= 2.7 Hz, C-sp), 114.7 (ArC), 115.3

(ArC), 123.1 (ArC), 124.1 (d, J_C,P= 11.9 Hz, C-sp²), 128.3 (ArC),

3

128.4 (ArC), 131.3 (ArC), 139.9 (d, J_C,P= 13.8 Hz, ArC), 145,1 (d,

²J_C,P= 6.7 Hz, C-sp²), 152.9 (ArC) ppm. HRMS (ESI): MNa⁺, found

434.1497. C₂₃H₂₆NNaO₄P requires 434.1492.

Synthesis of 2-alkynylcyclopent-1-enecarbaldehydes 1,¹⁶2-alkynyl-

cyclohex-1-enecarbaldehydes 2,¹⁵2-alkynylbenzaldehydes 3,¹⁷2-

alkynylindole-3-carbaldehydes 4,¹⁸2-alkynylpyridine-3-carbaldehydes

5,¹⁹2-alkynylquinoline-3-carbaldehydes 6,²⁰dimethyl 3-benzyl-2-

phenyl-2H-isoindol-1-ylphosphonate (11a),^5aand dimethyl 2,3-

diphenyl-1,2-dihydroisoquinolin-1-ylphosphonate (12a)^5awere per-

formed by methods reported in the literature.

Dimethyl (4-Ethoxyphenylamino)(2-(phenylethynyl)-

cyclopent-1-enyl)methylphosphonate (7c). Yellow solid, mp

139−141 °C. Yield 0.49 g, 57%. IR (KBr): υ_max3443 (NH), 2198

1

3

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.35 (3H, t, J = 6.8

Hz, CH₃), 1.78−1.96 (2H, m, CH₂CH₂CH₂), 2.38−2.47 (1H, m,

CH₂CH₂CH₂), 2.56−2.65 (3H, m, CH₂CH₂CH₂), 3.80 (3H, d, ³J_H,P

=

10.8 Hz, OCH₃), 3.84 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.93 (2H, q, ³J

3

= 6.8 Hz, CH₂CH₃) 4.93 (1H, d, J_H,P= 24.4 Hz, CH), 6.66−6.69

General Procedure for the Preparation of Compounds 7−9

and 19. To a solution of starting corresponding acetylenic aldehyde

1−4 (2 mmol) was added the corresponding aniline (2 mmol) and

dimethylphosphite (0.242 g, 2.2 mmol) in dry dichloromethane (5

mL) boron trifuoride etherate (0.284 g, 2 mmol). The resulting

solution was stirred at room temperature. When the completion of the

reaction was observed by TLC (after 12−24 h), the solution was

(2H, m, ArH), 6.73−6.77 (2H, m, ArH), 7.32−7.37 (3H, m, ArH),

7.47−7.49 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 15.0

(CH₃), 22.3 (CH₂), 32.7 (d, ³J_C,P= 1.2 Hz, CH₂), 36.8 (d, ⁵J_C,P= 2.2

1

2

Hz, CH₂), 52.2 (d, J_C,P= 153.8 Hz, CH), 53.6 (d, J_C,P= 7.1 Hz,

2

OCH₃), 53.9 (d, J_C,P= 6.8 Hz, OCH₃), 63.9 (OCH₂CH₃), 85.1 (d,

⁴J_C,P= 5.3 Hz, C-sp), 96.0 (d, ⁵J_C,P= 2.6 Hz, C-sp), 115.3 (ArC), 115.5

H

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

6

3

6

3

(ArC), 123.2 (d, J_C,P= 1.1 Hz, ArC), 124.1 (d, J_C,P= 12.8 Hz, C-

(d, J_C,P= 0.1 Hz, ArC), 124.3 (d, J_C,P= 12.8 Hz, C-sp²), 129.2

sp²), 128.3 (ArC), 128.4 (ArC), 131.4 (ArC), 140.0 (d, J_C,P= 16.0

(ArC), 131.3 (ArC), 138.6 (ArC), 140.1 (³d, J_C,P= 16.4 Hz, ArC),

3

Hz, ArC), 145.3 (d, J_C,P= 4.7 Hz, C-sp²), 152.3 (ArC) ppm. HRMS

144.8 (d, J_C,P= 4.8 Hz, C-sp²) ppm. HRMS (ESI): MNa⁺, found

2

(ESI): MNa⁺, found 448.1669. C₂₄H₂₈NNaO₄P requires 448.1648.

Dimethyl (4-Fluorophenylamino)(2-(phenylethynyl)-

cyclopent-1-enyl)methylphosphonate (7d). Yellow solid, mp

102−104 °C. Yield 0.56 g, 70%. IR (KBr): υ_max3453 (NH),

448.1642. C₂₄H₂₈NNaO₄P requires 448.1648.

Dimethyl (2-((4-Ethylphenyl)ethynyl)cyclopent-1-enyl)(4-

methoxyphenylamino)methylphosphonate (7h). Yellow solid,

mp 93−95 °C. Yield 0.35 g, 40%. IR (KBr): υ_max3448 (NH), 2202

2220(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.79−1.97 (2H,

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.24 (3H, t, J = 7.6

1

3

m, CH₂CH₂CH₂), 2.34−2.44 (1H, m, CH₂CH₂CH₂), 2.57−2.63 (3H,

Hz, CH₂CH₃), 1.77−1.95 (2H, m, CH₂CH₂CH₂), 2.37−2.46 (1H, m,

3

m, CH₂CH₂CH₂), 3.80 (3H, d, J_H,P= 10.8 Hz, OCH₃), 3.85 (3H, d,

CH₂CH₂CH₂), 2.55−2.62 (3H, m, CH₂CH₂CH₂), 2.66 (2H, q, J =

³J_H,P= 10.8 Hz, OCH₃), 4.93 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.62−6.65

(2H, m, ArH), 6.84−6.90 (2H, m, ArH), 7.33−7.36 (3H, m, ArH),

7.46−7.49 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 22.3

7.6 Hz, CH₂CH₃), 3.72 (3H, s, OCH₃), 3.79 (3H, d, J_H,P= 10.4 Hz,

3

OCH₃), 3.84 (3H, d, ³J_H₃_,P= 10.4 Hz, OCH₃), 4.94 (1H, d, ³J_H,P= 24.8

3

Hz, CH), 6.68 (2H, d, J = 9.2 Hz, ArH), 6.75 (2H, d, J = 8.8 Hz,

ArH), 7.18 (2H, d, ³J = 8.4 Hz, ArH), 7.40 (2H, d, ³J = 8.4 Hz, ArH)

3

5

(CH₂), 32.6 (d, J_C,P= 1.2 Hz, CH₂), 36.8 (d, J_C,P= 2.3 Hz, CH₂),

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 15.3 (CH₃), 22.2 (CH₂), 28.8

1

2

51.9 (d, J_C,P= 154.0 Hz, CH), 53.7 (d, J_C,P= 7.2 Hz, OCH₃), 53.9

3

5

(d, ²J_C,P= 6.8 Hz, OCH₃), 84.9 (d, ⁴J_C,P= 5.3 Hz, C-sp), 96.2 (d, ⁵J_C,P

(CH₂), 32.6 (d, J_C,P= 1.1 Hz, CH₂), 36.7 (d, J_C,P= 2.2 Hz, CH₂),

1

2

3

2

52.1 (d, J_C,P= 153.6 Hz, CH), 53.5 (d, J_C,P= 7.1 Hz, OCH₃), 53.8

= 2.6 Hz, C-sp), 114.8 (d, J_C,F= 7.4 Hz, ArC), 115.7 (d, J_C,F= 22.3

Hz, ArC), 123.0 (d, ⁶J_C,P= 0.9 Hz, ArC), 124.4 (d, ³J_C,P= 12.7 Hz, C-

sp²), 128.5 (ArC), 131.4 (ArC), 142.5 (dd, ³J_C,P= 16.3 Hz, ⁴J_C,F= 2.0

Hz, ArC), 144.9 (d, ²J_C,P= 4.9 Hz, C-sp²), 156.5 (d, ¹J_C,F= 234.9 Hz,

ArC) ppm. HRMS (ESI): MNa⁺, found 422.1283. C₂₂H₂₃FNNaO₃P

requires 422.1292.

(d, ²J_C,P= 6.7 Hz, OCH₃), 84.4 (d, ⁴J_C,P= 5.4 Hz, C-sp), 96.2 (d, ⁵J_C,P

6

= 2.6 Hz, C-sp), 114.7 (ArC), 115.2, (ArC), 120.3 (d, J_C,P= 1.1 Hz,

ArC), 124.3 (d, J_C,P= 12.9 Hz, C-sp²), 127.9 (ArC), 131.3 (ArC),

3

140.0 (d, ³J_C,P= 16.8 Hz, ArC), 144.7 (d, ²J_C,P= 4.6 Hz, C-sp²), 144.8

(ArC), 152.9 (ArC) ppm. HRMS (ESI): MNa⁺, found 462.1808.

C₂₅H₃₀NNaO₄P requires 462.1805.

Dimethyl (4-Chlorophenylamino)(2-(phenylethynyl)-

cyclopent-1-enyl)methylphosphonate (7e). Yellow solid, mp

129−131 °C. Yield 0.49 g, 59%. IR (KBr): υ_max3418 (NH), 2215

Dimethyl (2-(Hex-1-ynyl)cyclopent-1-enyl)(phenylamino)-

methylphosphonate (7i). Yellowish oil. Yield 0.36 g, 50%. IR

(KBr): υ_max3440 (NH), 2214 (CC) cm⁻¹. H NMR (300 MHz,

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.79−1.97 (2H, m,

1

CDCl₃): δ 0.94 (3H, t, ³J = 7.2 Hz, CH₂(CH₂)₂CH₃), 1.42−1.63 (4H,

m, CH₂(CH₂)₂CH₃), 1.69−1.91 (2H, m, CH₂CH₂CH₂), 2.29−2.55

(6H, m, CH₂CH₂CH₂and CH₂(CH₂)₂CH₃), 3.77 (3H, d, ³J_H,P= 10.5

CH₂CH₂CH₂), 2.34−2.43 (1H, m, CH₂CH₂CH₂), 2.58−2.63 (3H, m,

CH₂CH₂CH₂), 3.80 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.84 (3H, d, ³J_H,P

= 10.8 Hz, OCH₃), 4.94 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.13−6.65 (2H,

m, ArH), 7.09−7.13 (2H, m, ArH), 7.33−7.37 (3H, m, ArH), 7.46−

7.49 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 22.2 (CH₂),

Hz, OCH₃), 3.82 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 4.78 (1H, d, ³J_H,P

=

24.6 Hz, CH), 6.66−6,69 (2H, m, ArH), 6.71−6.76 (1H, m, ArH),

7.13−7.18 (2H, m, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 13.5

(CH₃), 19.3 (CH₂), 21.9 (CH₂), 22.0 (CH₂), 32.0 (CH₂), 36.9 (d,

3

5

32.6 (d, J_C,P= 1.1 Hz, CH₂), 36.7 (d, J_C,P= 2.4 Hz, CH₂), 51.3 (d,

¹J_C,P= 153.9 Hz, CH), 53.6 (d, ²J_C,P= 7.2 Hz, OCH₃), 53.8 (d, ²J_C,P

6.8 Hz, OCH₃), 84.8 (d, ⁴J_C,P= 5.3 Hz, C-sp), 96.3 (d, ⁵J_C,P= 2.6 Hz,

=

⁵J_C,P= 2.1 Hz, CH₂), 50.9 (d, J_C,P= 154.2 Hz, CH), 53.5 (d, J_C,P

=

1

2

6

3

C-sp), 114.9 (ArC), 123.0 (d, J_C,P= 0.9 Hz, ArC), 124.4 (d, J_C,P

=

7.3 Hz, OCH₃), 53.6 (d, ²J_C,P= 6.9 Hz, OCH₃), 76.2 (d, ⁴J_C,P= 5.4 Hz,

C-sp), 97.3 (d, ⁵J_C,P= 2.2 Hz, C-sp), 113.7 (ArC), 118.5 (ArC), 124.9

12.7 Hz, C-sp²), 128.4 (ArC), 128.4 (ArC), 129.0 (ArC), 131.3 (ArC),

144.5 (d, ²J_C,P= 5.0 Hz, C-sp²), 144.8 (d, ³J_C,P= 15.8 Hz, ArC) ppm.

HRMS (ESI): MNa⁺, found 438.0999. C₂₂H₂₃ClNNaO₃P requires

438.0996.

3

2

(d, J_C,P= 13.0 Hz, C-sp²), 129.1 (ArC), 142.3 (d, J_C,P= 4.4 Hz, C-

sp²), 146.2 (d, ³J_C,P= 15.5 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found

384.1698. C₂₀H₂₈NNaO₃P requires 384.1704.

Dimethyl (Phenylamino)(2-(p-tolylethynyl)cyclopent-1-

enyl)methylphosphonate (7f). Yellow solid, mp 143−145 °C.

Yield 0.65 g, 82%. IR (KBr): υ_max3402 (NH), 2179 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 1.78−1.96 (2H, m, CH₂CH₂CH₂), 2.37

(3H, s, CH₃), 2.40−2.47 (1H, m, CH₂CH₂CH₂), 2.57−2.67 (3H, m,

CH₂CH₂CH₂), 3.80 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.84 (3H, d, ³J_H,P

= 10.8 Hz, OCH₃), 5.01 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.70−6.77 (3H,

m, ArH), 7.15−7.19 (4H, m, ArH), 7.37−7.39 (2H, m, ArH) ppm. ¹³C

Dimethyl (2-(Hex-1-ynyl)cyclopent-1-enyl)(4-

methoxyphenylamino)methylphosphonate (7j). Yellowish oil.

Yield 0.46 g, 59%. IR (KBr): υ_max3418 (NH), 2211 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 0.94 (3H, t, ³J = 7.6 Hz,

CH₂(CH₂)₂CH₃), 1.43−1.61 (4H, m, CH₂(CH₂)₂CH₃), 1.69−1.88

(2H, m, CH₂CH₂CH₂), 2.26−2.56 (6H, m, CH₂CH₂CH₂and

3

CH₂(CH₂)₂CH₃), 3.72 (3H, s, OCH₃), 3.76 (3H, d, J_H,P= 10.8

Hz, OCH₃), 3.81 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 4.83 (1H, d, ³J_H,P

=

NMR (100 MHz, CDCl₃): δ 21.5 (CH₃), 22.2 (CH₂), 32.6 (d, ³J_C,P

=

24.4 Hz, CH), 6.62 (2H, d, ³J = 9.2 Hz, ArH), 6.74 (2H, d, ³J = 9.2 Hz,

1.5 Hz, CH₂), 36.7 (d, ⁵J_C,P= 2.3 Hz, CH₂), 51.1 (d, ¹J_C,P= 153.6 Hz,

CH), 53.6 (d, ²J_C,P= 7.1 Hz, OCH₃), 53.8 (d, ²J_C,P= 6.7 Hz, OCH₃),

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.5 (CH₃), 19.3 (CH₂),

21.9 (CH₂), 22.0 (CH₂), 32.0 (d, ³J_C,P= 1.0 Hz, CH₂), 36.9 (d, ⁵J_C,P

=

4

5

2

2.3 Hz, CH₂), 51.7 (d, ¹J_C,P= 154.2 Hz, CH), 53.4 (d, J_C,P= 7.1 Hz,

84.4 (d, J_C,P= 5.3 Hz, C-sp), 96.2 (d, J_C,P= 2.8 Hz, C-sp), 113.7

6

3

OCH₃), 53.6 (d, ²J_C,P= 6.7 Hz, OCH₃), 55.5 (OCH₃), 76.3 (d, ⁴J_C,P

=

(ArC), 118.6, (ArC), 120.0 (d, J_C,P= 1.1 Hz, ArC), 124.1 (d, J_C,P

=

12.6 Hz, C-sp²), 129.1 (ArC), 129.2 (ArC), 131.2 (ArC), 131.3 (ArC),

138.5 (ArC), 144.6 (d, ²J_C,P= 4.7 Hz, C-sp²), 146.2 (d, ³J_C,P= 14.0 Hz,

ArC) ppm. HRMS (ESI): MNa⁺, found 418.1542. C₂₃H₂₆NNaO₃P

requires 418.1543.

5

5.2 Hz, C-sp), 97.1 (d, J_C,P= 2.5 Hz, C-sp), 114.6 (ArC), 115.0

3

(ArC), 124.9 (d, J_C,P= 13.0 Hz, C-sp²), 140.2 (d, J_C,P= 16.6 Hz,

2

ArC), 142.6 (d, J_C,P= 4.5 Hz, C-sp²), 152.7 (ArC) ppm. HRMS

(ESI): MNa⁺, found 414.1785. C₂₁H₃₀NNaO₄P requires 414.1810.

Dimethyl (4-Fluorophenylamino)(2-(hex-1-ynyl)cyclopent-

1-enyl)methylphosphonate (7k). Yellow solid, mp 68−70 °C.

Yield 0.42 g, 55%. IR (KBr): υ_max3469 (NH), 2216 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 0.94 (3H, t, ³J = 7.6 Hz,

CH₂(CH₂)₂CH₃), 1.43−1.52 (2H, m, CH₂CH₂CH₂CH₃), 1.54−1.61

(2H, m, CH₂CH₂CH₂CH₃), 1.70−1.89 (2H, m, CH₂CH₂CH₂), 2.25−

2.34 (1H, m, CH₂CH₂CH₂), 2.41−2.57 (5H, m, CH₂CH₂CH₂and

Dimethyl (4-Methoxyphenylamino)(2-(p-tolylethynyl)-

cyclopent-1-enyl)methylphosphonate (7g). Yellow solid, mp

110−112 °C. Yield 0.63 g, 74%. IR (KBr): υ_max3488 (NH), 2197

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.77−1.95 (2H, m,

CH₂CH₂CH₂), 2.36 (3H, s, CH₃), 2.39−2.45 (1H, m, CH₂CH₂CH₂),

2.55−2.66 (3H, m, CH₂CH₂CH₂), 3.72 (3H, s, OCH₃), 3.79 (3H, d,

3

³J_H,P= 10.8 Hz, OCH₃), 3.84 (3H, d, J_H,P= 10.8 Hz, OCH₃), 4.80

3

CH₂(CH₂)₂CH₃), 3.77 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.82 (3H, d,

(1H, d, J_H,P= 24.4 Hz, CH), 6.68 (2H, d, J = 8.8 Hz, ArH), 7.15

(2H, d, ³J = 8.8 Hz, ArH), 7.15 (2H, d, ³J = 7.6 Hz, ArH), 7.37 (2H, d,

³J = 8.0 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.5 (CH₃),

³J_H,P= 10.4 Hz, OCH₃), 4.83 (1H, d, ³J_H,P= 24.4 Hz, CH), 6.58−6.61

(2H, m, ArH), 6.83−6.88 (2H, m, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 13.5 (CH₃), 19.3 (CH₂), 21.9 (CH₂), 22.1 (CH₂), 30.9

3

5

22.3 (CH₂), 32.6 (d, J_C,P= 1.1 Hz, CH₂), 36.8 (d, J_C,P= 2.2 Hz,

CH₂), 52.1 (d, ¹J_C,P= 153.6 Hz, CH), 53.6 (d, ²J_C,P= 7.1 Hz, OCH₃),

53.9 (d, ²J_C,P= 6.7 Hz, OCH₃), 55.6 (OCH₃), 84.5 (d, ⁴J_C,P= 5.4 Hz,

C-sp), 96.2 (d, ⁵J_C,P= 2.7 Hz, C-sp), 114.7 (ArC), 115.3, (ArC), 120.1

3

5

(CH₂), 32.0 (d, J_C,P= 1.0 Hz, CH₂), 36.9 (d, J_C,P= 2.3 Hz, CH₂),

1

2

51.5 (d, J_C,P= 154.3 Hz, CH), 53.5 (d, J_C,P= 7.1 Hz, OCH₃), 53.6

(d, ²J_C,P= 6.8 Hz, OCH₃), 76.2 (d, ⁴J_C,P= 5.2 Hz, C-sp), 97.4 (d, ⁵J_C,P

I

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The Journal of Organic Chemistry

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= 2.5 Hz, C-sp), 114.7 (d, ³J_C,F= 7.4 Hz, ArC), 115.5, (d, ²J_C,F= 22.2

Hz, ArC), 125.3 (d, ³J_C,P= 12.9 Hz, C-sp²), 142.1 (d, ²J_C,P= 4.6 Hz, C-

NMR (75 MHz, CDCl₃): δ 0.3 (CH(CH₂)₂), 8.9 (CH(CH₂)₂), 9.0

(CH(CH₂)₂), 22.0 (CH₂), 32.1 (CH₂), 36.8 (d, ⁵J_C,P= 2.2 Hz, CH₂),

sp²), 142.5 (dd, ³J_C,P= 16.2 Hz, ⁴J_C,F= 1.8 Hz, ArC), 156.3 (d, ¹J_C,F

=

50.9 (d, J_C,P= 154.2 Hz, CH), 53.5 (d, J_C,P= 7.1 Hz, OCH₃), 53.7

1

2

234.7 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 402.1603.

C₂₀H₂₇FNNaO₃P requires 402.1605.

(d, ²J_C,P= 6.7 Hz, OCH₃), 71.3 (d, ⁴J_C,P= 5.1 Hz, C-sp), 100.4 (d, ⁵J_C,P

3

= 2.5 Hz, C-sp), 113.6 (ArC), 118.4 (ArC), 124.6 (d, J_C,P= 13.2 Hz,

C-sp²), 129.1 (ArC), 142.8 (d, ²J_C,P= 4.5 Hz, C-sp²), 146.3 (d, ³J_C,P

=

Dimethyl (4-Chlorophenylamino)(2-(hex-1-ynyl)cyclopent-

1-enyl)methylphosphonate (7l). Yellow solid, mp 73−75 °C.

Yield 0.36 g, 45%. IR (KBr): υ_max3433 (NH), 2213 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 0.94 (3H, t, ³J = 7.2 Hz,

CH₂(CH₂)₂CH₃), 1.42−1.51 (2H, m, CH₂CH₂CH₂CH₃), 1.53−1.61

(2H, m, CH₂CH₂CH₂CH₃), 1.70−1.89 (2H, m, CH₂CH₂CH₂), 2.26−

2.31 (1H, m, CH₂CH₂CH₂), 2.41−2.55 (5H, m, CH₂CH₂CH₂and

16.6 Hz, ArC) ppm. HRMS (ESI): MH⁺, found 346.1569.

C₁₉H₂₅NO₃P requires 346.1567.

Dimethyl (2-(Cyclopropylethynyl)cyclopent-1-enyl)(4-

methoxyphenylamino)methylphosphonate (7p). Yellowish oil.

Yield 0.41 g, 55%. IR (KBr): υ_max3451 (NH), 2211 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 0.73−0.77 (2H, m, CH(CH₂)₂), 0.86−

0.90 (2H, m, CH(CH₂)₂), 1.42−1.48 (1H, m, CH(CH₂)₂), 1.69−1.87

(2H, m, CH₂CH₂CH₂), 2.27−2.56 (4H, m, CH₂CH₂CH₂), 3.73 (3H,

3

CH₂(CH₂)₂CH₃), 3.76 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.81 (3H, d,

³J_H,P= 10.8 Hz, OCH₃), 4.84 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.58 (2H,

3

d, J = 9.2 Hz, ArH), 7.09 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ 13.5 (CH₃), 19.2 (CH₂), 21.9 (CH₂), 22.0

(CH₂), 30.9 (CH₂), 32.0 (d, ³J_C,P= 1.1 Hz, CH₂), 36.8 (d, ⁵J_C,P= 2.2

s, OCH₃), 3.76 (3H, d, J_H,P= 10.8 Hz, OCH₃), 3.82 (3H, d, J_H,P

=

10.8 Hz, OCH₃), 4.79 (1H, d, ³J_H,P= 24.4 Hz, CH), 6.61 (2H, d, ³J =

9.2 Hz, ArH), 6.75 (1H, d, J = 9.2 Hz, ArH) ppm. ¹³C NMR (100

3

1

2

MHz, CDCl₃): δ 0.42 (CH(CH₂)₂), 8.9 (CH(CH₂)₂), 9.0 (CH-

Hz, CH₂), 51.0 (d, J_C,P= 154.3 Hz, CH), 53.5 (d, J_C,P= 4.3 Hz,

(CH₂)₂), 22.1 (CH₂), 32.2 (d, ³J_C,P= 1.2 Hz, CH₂), 36.9 (d, ⁵J_C,P= 2.1

OCH₃), 53.6 (d, ²J_C,P= 3.9 Hz, OCH₃), 76.1 (d, ⁴J_C,P= 5.3 Hz, C-sp),

1

2

5

Hz, CH₂), 51.8 (d, J_C,P= 154.0 Hz, CH), 53.4 (d, J_C,P= 7.1 Hz,

97.5 (d, J_C,P= 2.4 Hz, C-sp), 114.9 (ArC), 123.1 (ArC), 125.4 (d,

OCH₃), 53.7 (d, ²J_C,P= 6.7 Hz, OCH₃), 55.6 (OCH₃), 71.4 (d, ⁴J_C,P

=

³J_C,P= 12.9 Hz, C-sp²), 128.9 (ArC), 141.8 (d, J_C,P= 4.6 Hz, C-sp²),

2

5

144.8 (d, J_C,P= 16.6 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found

3

5.3 Hz, C-sp), 100.4 (d, J_C,P= 2.3 Hz, C-sp), 114.6 (ArC), 115.1

(ArC), 124.6 (d, J_C,P= 13.0 Hz, C-sp²), 140.2 (d, J_C,P= 16.4 Hz,

3

418.1301. C₂₀H₂₇ClNNaO₃P requires 418.1309.

ArC), 143.0 (d, J_C,P= 4.5 Hz, C-sp²), 152.7 (ArC) ppm. HRMS

2

Dimethyl (2-(Hept-1-ynyl)cyclopent-1-enyl)(phenylamino)-

(ESI): MNa⁺, found 398.1487. C₂₀H₂₆NNaO₄P requires 398.1492.

Dimethyl (2-(Cyclopropylethynyl)cyclopent-1-enyl)(4-

ethoxyphenylamino)methylphosphonate (7r). Yellow solid, mp

139−141 °C. Yield 0.44 g, 57%. IR (KBr): υ_max3460 (NH), 2212

methylphosphonate (7m). Yellowish oil. Yield 0.31 g, 41%. IR

1

(KBr): υ_max3409 (NH), 2216 (CC) cm⁻¹. H NMR (400 MHz,

CDCl₃): δ 0.91 (3H, t, ³J = 7.6 Hz, CH₂(CH₂)₃CH₃), 1.30−1.39 (2H,

m, CH₂(CH₂)₂CH₂CH₃), 1.40−1.48 (2H, m, CH₂CH₂CH₂CH₂CH₃),

1.60 (2H, quint, ³J = 7.2 Hz, CH₂CH₂CH₂CH₂CH₃), 1.71−1.89 (2H,

m, CH₂CH₂CH₂), 2.31−2.59 (6H, m, CH₂CH₂CH₂and

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 0.73−0.77 (2H, m,

1

CH(CH₂)₂), 0.85−0.90 (2H, m, CH(CH₂)₂), 1.35 (3H, t, ³J = 7.2 Hz,

OCH₂CH₃), 1.41−1.48 (1H, m, CH(CH₂)₂), 1.68−1.87 (2H, m,

3

CH₂(CH₂)₃CH₃), 3.77 (3H, d, J_H,P= 10.8 Hz, OCH₃), 3.82 (3H,

CH₂CH₂CH₂), 2.26−2.54 (4H, m, CH₂CH₂CH₂), 3.76 (3H, d, ³J_H,P

=

3

d, J_H,P= 10.4 Hz, OCH₃), 4.92 (1H, d, J_H,P= 24.8 Hz, CH), 6.67

(2H, d, ³J = 7.6 Hz, ArH), 6.74 (1H, t, ³J = 7.6 Hz, ArH), 7.16 (2H, t,

³J = 7.6 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.9 (CH₃),

19.6 (CH₂), 22.0 (CH₂), 22.2 (CH₂), 28.5 (CH₂), 31.0 (CH₂), 32.0

10.4 Hz, OCH₃), 3.82 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.94 (2H, q, ³J

= 7.2 Hz, OCH₂CH₃), 4.79 (1H, d, ³J_H,P= 24.4 Hz, CH), 6.59 (2H, d,

³J = 8.8 Hz, ArH), 6.74 (1H, d, ³J = 8.8 Hz, ArH) ppm. ¹³C NMR (100

MHz, CDCl₃): δ 0.38 (CH(CH₂)₂), 8.9 (CH(CH₂)₂), 9.0 (CH-

(d, ³J_C,P= 1.0 Hz, CH₂), 36.9 (d, ⁵J_C,P= 2.3 Hz, CH₂), 50.9 (d, ¹J_C,P

=

3

154.0 Hz, CH), 53.5 (d, ²J_C,P= 7.0 Hz, OCH₃), 53.7 (d, ²J_C,P= 6.8 Hz,

(CH₂)₂), 14.9 (OCH₂CH₃), 22.1 (CH₂), 32.2 (d, J_C,P= 1.0 Hz,

CH₂), 36.9 (d, J_C,P= 2.3 Hz, CH₂), 51.7 (d, J_C,P= 154.1 Hz, CH),

53.4 (d, J_C,P= 7.1 Hz, OCH₃), 53.7 (d, J_C,P= 6.7 Hz, OCH₃), 63.8

5

1

4

5

OCH₃), 76.2 (d, J_C,P= 5.3 Hz, C-sp), 97.3 (d, J_C,P= 2.5 Hz, C-sp),

2

113.7 (ArC), 118.5 (ArC), 124.9 (d, J_C,P= 13.0 Hz, C-sp²), 129.1

3

4

5

(ArC), 142.3 (d, ²J_C,P= 4.5 Hz, C-sp²), 146.2 (d, ³J_C,P= 15.4 Hz, ArC)

ppm. HRMS (ESI): MNa⁺, found 398.1851. C₂₁H₃₀NNaO₃P requires

398.1856.

(OCH₂CH₃), 71.4 (d, J_C,P= 5.4 Hz, C-sp), 100.3 (d, J_C,P= 2.4 Hz,

C-sp), 115.0 (ArC), 115.4 (ArC), 124.5 (d, J_C,P= 12.9 Hz, C-sp²),

3

140.2 (d, ³J_C,P= 16.4 Hz, ArC), 143.1 (d, ²J_C,P= 4.5 Hz, C-sp²), 152.0

(ArC) ppm. HRMS (ESI): MH⁺, found 390.1844. C₂₁H₂₉NO₄P

requires 390.1829.

Dimethyl (2-(Hept-1-ynyl)cyclopent-1-enyl)(4-

methoxyphenylamino)methylphosphonate (7n). Yellowish oil.

Yield 0.41 g, 50%. IR (KBr): υ_max3450 (NH), 2221 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 0.91 (3H, t, ³J = 7.2 Hz,

CH₂(CH₂)₃CH₃), 1.30−1.37 (2H, m, CH₂(CH₂)₂CH₂CH₃), 1.39−

Dimethyl (Phenylamino)(2-((trimethylsilyl)ethynyl)-

cyclopent-1-enyl)methylphosphonate (7s-TMS). Yellow solid,

mp 141−143 °C. Yield 0.41 g, 54%. IR (KBr): υ_max3437 (NH), 2134

(CC), cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 0.24 (9H, s,

Si(CH₃)₃), 1.73−1.91 (2H, m, CH₂CH₂CH₂), 2.35−2.60 (4H, m,

CH₂CH₂CH₂), 3.78 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.83 (3H, d, ³J_H,P

= 10.8 Hz, OCH₃), 4.93 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.68 (2H, d, ³J

3

1.47 (2H, m, CH₂CH₂CH₂CH₂CH₃), 1.59 (2H, quint, J = 7.2 Hz,

CH₂CH₂CH₂CH₂CH₃), 1.70−1.88 (2H, m, CH₂CH₂CH₂), 2.30−2.56

(6H, m, CH₂CH₂CH₂and CH₂(CH₂)₃CH₃), 3.73 (3H, s, OCH₃),

3

3.77 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.82 (3H, d, J_H,P= 10.4 Hz,

3

= 7.6 Hz, ArH), 6.76 (1H, t, J = 7.6 Hz, ArH), 7.15−7.19 (2H, m,

OCH₃), 4.84 (1H, d, J_H,P= 24.4 Hz, CH), 6.65 (2H, d, J = 9.2 Hz,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 0.0 (Si(CH₃)₃), 22.2

ArH), 6.75 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

3

5

(CH₂), 32.5 (d, J_C,P= 1.2 Hz, CH₂), 36.5 (d, J_C,P= 2.1 Hz, CH₂),

CDCl₃): δ 13.9 (CH₃), 19.6 (CH₂), 22.1 (CH₂), 22.2 (CH₂), 28.5

1

2

(CH₂), 31.0 (CH₂), 32.0 (CH₂), 36.9 (d, ⁵J_C,P= 2.2 Hz, CH₂), 51.9 (d,

50.9 (d, J_C,P= 153.3 Hz, CH), 53.5 (d, J_C,P= 7.1 Hz, OCH₃), 53.8

2

4

¹J_C,P= 154.3 Hz, CH), 53.5 (d, ²J_C,P= 7.0 Hz, OCH₃), 53.7 (d, ²J_C,P

=

(d, J_C,P= 6.8 Hz, OCH₃), 101.0 (d, J_C,P= 5.0 Hz, C-sp), 101.3 (d,

⁵J_C,P= 2.1 Hz, C-sp), 113.7 (ArC), 118.6 (ArC), 124.2 (d, ³J_C,P= 12.6

6.7 Hz, OCH₃), 55.6 (OCH₃), 76.2 (d, ⁴J_C,P= 5.3 Hz, C-sp), 97.3 (d,

⁵J_C,P= 2.5 Hz, C-sp), 114.6 (ArC), 115.4 (ArC), 125.1 (d, ³J_C,P= 13.1

Hz, C-sp²), 129.2 (ArC), 146.1 (d, J_C,P= 15.2 Hz, ArC), 146.5 (d,

3

²J_C,P= 4.2 Hz, C-sp²) ppm. HRMS (ES): MNa⁺, found 400.1464.

Hz, C-sp²), 139.8 (d, ³J_C,P= 16.2 Hz, ArC), 142.3 (d, ²J_C,P= 4.6 Hz, C-

sp²), 152.9 (ArC) ppm. HRMS (ESI): MNa⁺, found 428.1958.

C₂₂H₃₂NNaO₄P requires 428.1961.

C₁₉H₂₈NNaO₃PSi requires 400.1468.

Dimethyl (2-Ethynylcyclopent-1-enyl)(phenylamino)-

methylphosphonate (7s). This compound was synthesized from

7s-TMS by treating by 2 equiv of KF₂·H₂O in methanol at room

temperature for 2 h. After evaporation of solvent, the residue was

puriﬁed by column chromatography. Yellow solid, mp 118−119 °C.

Yield 0.27 g, 83%. IR (KBr): υ_max3452 (NH), 2088 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 1.74−1.92 (2H, m, CH₂CH₂CH₂), 2.34−

2.40 (1H, m, CH₂CH₂CH₂), 2.49−2.61 (3H, m, CH₂CH₂CH₂), 3.38

(1H, br. s, CCH), 3.78 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.83 (3H, d,

³J_H,P= 10.8 Hz, OCH₃), 4.93 (1H, d, ³J_H,P= 24.8 Hz, CH), 6.64−6.67

Dimethyl (2-(Cyclopropylethynyl)cyclopent-1-enyl)-

(phenylamino)methylphosphonate (7o). Yellow solid, mp 143−

145 °C. Yield 0.37 g, 53%. IR (KBr): υ_max3407 (NH), 2211 (CC)

cm⁻^{1 1}H NMR (300 MHz, CDCl₃): δ 0.73−0.78 (2H, m,

.

CH(CH₂)₂), 0.85−0.92 (2H, m, CH(CH₂)₂), 1.41−1.50 (1H, m,

CH(CH₂)₂), 1.67−1.89 (2H, m, CH₂CH₂CH₂), 2.27−2.58 (4H, m,

CH₂CH₂CH₂), 3.77 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.82 (3H, d, ³J_H,P

= 10.8 Hz, OCH₃), 4.86 (1H, d, ³J_H,P= 24.9 Hz, CH), 6.63−6.67 (2H,

m, ArH), 6.71−6.76 (1H, m, ArH), 7.12−7.19 (2H, m, ArH) ppm. ¹³C

J

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The Journal of Organic Chemistry

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4

5

(2H, m, ArH), 6.73−6.77 (1H, m, ArH), 7.14−7.19 (2H, m, ArH)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 22.0 (CH₂), 32.4 (d, ³J_C,P= 1.1

151.0 Hz, CH), 88.3 (d, J_C,P= 5.1 Hz, C_sp), 94.8 (d, J_C,P= 2.2 Hz,

C_sp), 114.7 (ArC), 121.2 (d, ³J_C,P= 12.4 Hz, C_sp), 123.0 (ArC), 123.1

2

5

1

6

Hz, CH₂), 36.6 (d, J_C,P= 2.3 Hz, CH₂), 50.9 (d, J_C,P= 153.5 Hz,

(d, J_C,P= 0.8 Hz, ArC), 128.3 (ArC), 128.4 (ArC), 129.1 (ArC),

3

CH), 53.5 (d, ²J_C,P= 7.2 Hz, OCH₃), 53.8 (d, ²J_C,P= 6.7 Hz, OCH₃),

131.3 (ArC), 138.9 (d, ²J_C,P= 4.0 Hz, C_sp), 144.9 (d, J_C,P= 16.3 Hz,

2

4

5

79.4 (d, J_C,P= 5.2 Hz, C-sp), 83.9 (d, J_C,P= 2.6 Hz, C-sp), 113.6

ArC) ppm. HRMS (ESI): MNa⁺, found 452.1145. C₂₃H₂₅ClNNaO₃P

requires 452.1153.

(ArC), 118.6 (ArC), 123.1 (d, J_C,P= 12.7 Hz, C-sp²), 129.2 (ArC),

3

146.1 (d, ³J_C,P= 15.4 Hz, ArC), 146.9 (d, J_C,P= 4.6 Hz, C-sp²) ppm.

Dimethyl (Phenylamino)(2-(p-tolylethynyl)cyclohex-1-enyl)-

methylphosphonate (8e). Light orange solid, mp 133−134 °C.

Yield 0.43 g, 53%. IR (KBr): υ_max3304 (NH), 2201 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 1.54−1.65 (4H, m, 2 × CH₂), 2.05−2.08

(1H, m, CHH), 2.33 (3H, br. s, CHH, CH₂), 2.36 (3H, s, CH₃), 3.80

(3H, d, J_H,P= 6.4 Hz, OCH₃), 3.82 (3H, d, J_H,P= 6.4 Hz, OCH₃),

5.29 (1H, d, ²J_H,P= 26.0 Hz, CHNH), 6.70−6.76 (3H, m, ArH), 7.16

(4H, dd, J = 13.3; 7.6 Hz ArH), 7.37 (2H, d, J = 7.6 Hz ArH), 7.47−

7.49 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.5 (CH₃),

2

HRMS (ESI): MH⁺, found 306.1261. C₁₆H₂₁NO₃P requires 306.1254.

Dimethyl (Phenylamino)(2-(phenylethynyl)cyclohex-1-

enyl)methylphosphonate (8a). Light Orange solid, mp 139−140

°C. Yield 0.39 g, 49%. IR (KBr): υ_max2200 (CC) 3405 (NH),cm⁻¹.

¹H NMR (400 MHz, CDCl₃): δ 1.54−1.62 (4H, m, 2 × CH₂), 2.04−

3

2.17 (1H, m, CHH), 2.32−2.34 (3H, m, CHH, CH₂), 3.80 (3H, d,

³J_H,P= 6.8 Hz, OCH₃), 3.83 (3H, d, ³J_H,P= 6.8 Hz, OCH₃), 5.29 (1H,

d, ²J_H,P= 25.6 Hz, CHNH), 6.70−6.76 (3H, m, ArH), 7.16−7.20 (2H,

m, ArH), 7.33−7.35 (3H, m, ArH), 7.47−7.49 (2H, m, ArH) ppm. ¹³C

4

22.0 (2 × CH₂), 24.8 (CH₂), 30.4 (d, J_C,P= 1.8 Hz, CH₂), 53.6 (d,

²J_C,P= 6.8 Hz, OCH₃), 53.8 (d, ²J_C,P= 7.0 Hz, OCH₃), 54.7 (d, ¹J_C,P

=

NMR (100 MHz, CDCl₃): δ 21.9 (CH₂), 22.0 (CH₂), 24.8 (d, ³J_C,P

=

4

5

4

2

150.2 Hz, CH), 87.9 (d, J_C,P= 5.2 Hz, C_sp), 94.8 (d, J_C,₃_P= 1.8 Hz,

1.5 Hz, CH₂), 30.4 (d, J_C,P= 1.9 Hz, CH₂), 53.7 (d, J_C,P= 6.9 Hz,

2

1

C_sp), 113.5 (ArC), 118.3 (ArC), 120.3 (ArC), 120.9 (d, J_C,P= 12.6

OCH₃), 53.8 (d, J_C,P= 7.1 Hz, OCH₃), 54.8 (d, J_C,P= 150.5 Hz,

CH), 88.5 (d, J_C,P= 5.2 Hz, C_sp), 94.6 (d, ⁵J_C,P= 2.2 Hz, C_sp), 113.5

4

2

Hz, C_sp), 129.2 (ArC), 129.3 (ArC), 131.2 (ArC), 138.4 (ArC), 139.0

2

3

2

(d, J_C,P= 4.0 Hz, C_sp), 146.3 (d, J_C,P= 15.8 Hz, ArC) ppm. HRMS

(ESI): MNa⁺, found 432.1699. C₂₄H₂₈NNaO₃P requires 432.1699.

Dimethyl (4-Methoxyphenylamino)(2-(p-tolylethynyl)-

cyclohex-1-enyl)methylphosphonate (8f). Light orange solid,

mp 96−97 °C. Yield 0.39 g, 44%. IR (KBr): υ_max3503 (NH), 2197

(ArC), 118.3 (ArC), 120.8 (d, J_C,P= 12.4 Hz, C_sp), 123.3 (ArC),

128.2 (ArC), 128.4 (ArC), 129.3 (ArC), 131.3 (ArC), 139.5 (d, ²J_C,P

=

3

2

3.7 Hz, C_sp), 146.3 (d, J_C,P= 16.0 Hz, ArC) ppm. HRMS (ESI):

MNa⁺, found 418.1547. C₂₃H₂₆NNaO₃P requires 418.1543.

Dimethyl (4-Methoxyphenylamino)(2-(phenylethynyl)-

cyclohex-1-enyl)methylphosphonate (8b). Brownish solid, mp

142−141 °C. Yield 0.43 g, 51%. IR (KBr): υ_max3343 (NH), 2202

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.50−1.66 (4H, m, 2

1

× CH₂), 2.01−2.08 (1H, m, CHH), 2.28−2.31 (3H, m, CHH, CH₂),

3

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.52−1.65 (4H, m, 2

2.36 (3H, s, CH₃), 3.72 (3H, s, OCH₃), 3.79 (3H, d, J_H,P= 10.4 Hz,

OCH₃), 3.82 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 5.22 (1H, d, ²J_H,P= 25.6

Hz, CHNH), 6.67 (2H, d, J = 9.2 Hz ArH), 6.76 (2H, d, J = 9.2 Hz

ArH), 7.14 (2H, d, J = 8.0 Hz ArH), 7.36 (2H, d, J = 8.0 Hz ArH)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.5 (CH₃), 22.0 (2 × CH₂),

× CH₂), 2.02−2.08 (1H, m, CHH), 2.31−2.39 (3H, m, CHH, CH₂),

3.73 (3H, s, OCH₃), 3.79 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.83 (3H, d,

2

³J_H,P= 10.4 Hz, OCH₃), 5.22 (1H, d, J_H,P= 25.6 Hz, CHNH), 6.67

(2H, d, J = 8.8 Hz, ArH), 6.76 (2H, d, J = 9.2 Hz, ArH), 7.31−7.35

(3H, m, ArH), 7.46−7.49 (2H, m, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 21.9 (CH₂), 22.0 (CH₂), 24.8 (d, ³J_C,P= 1.2 Hz, CH₂), 30.4

(d, ⁴J_C,P= 1.8 Hz, CH₂), 53.6 (d, ²J_C,P= 2.6 Hz, OCH₃), 53.7 (d, ²J_C,P

= 2.9 Hz, OCH₃), 55.6 (d, ¹J_C,P= 150.8 Hz, CH), 55.6 (OCH₃), 88.6

3

4

24.8 (d, J_C,P= 1.1 Hz, CH₂), 30.4 (d, J_C,P= 1.7 Hz, CH₂), 53.7 (d,

²J_C,P= 3.8 Hz, OCH₃), 53.7 (d, ²J_C,P= 3.9 Hz, OCH₃), 55.6 (d, ¹J_C,P

=

4

150.6 Hz, CH), 55.6 (OCH₃), 88.0 (d, J_C,P= 5.2 Hz, C_sp), 94.7 (d,

⁵J_C,P= 2.0 Hz, C_sp), 114.8 (ArC), 115.0 (ArC), 120.3 (ArC), 121.1 (d,

3

4

5

2

J_C,P= 12.4 Hz, C_sp), 129.2 (ArC), 131.2 (ArC), 138.4 (ArC), 139.1

(d, J_C,P= 5.0 Hz, C_sp), 94.5 (d, J_C,P= 2.2 Hz, C_sp), 114.8 (ArC),

3

2

3

2

114.9 (ArC), 120.9 (d, J_C,P= 12.4 Hz, C_sp), 123.3 (ArC), 128.2

(d, J_C,P= 3.6 Hz, C_sp), 140.1 (d, J_C,P= 15.9 Hz, ArC), 152.7 (ArC)

ppm. HRMS (ESI): MNa⁺, found 462.1795. C₂₅H₃₀NNaO₄P requires

462.1805.

(ArC), 128.4 (ArC), 131.3 (ArC), 139.6 (d, ²J_C,P= 3.6 Hz, C_sp), 140.1

2

3

(d, J_C,P= 16.9 Hz, ArC), 152.7 (ArC) ppm. HRMS (ESI): MNa⁺,

found 448.1641. C₂₄H₂₈NNaO₄P requires 448.1648.

Dimethyl (2-(Pent-1-ynyl)cyclohex-1-enyl)(phenylamino)-

methylphosphonate (8g). Light orange solid, mp 65−66 °C.

Yield 0.18 g, 25%. IR (KBr): υ_max3434 (NH), 2216 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 1.05 (3H, t, J = 7.6 Hz, CH₃), 1.46−1.56

(4H, m, 2 × CH₂), 1.62 (2H, sexst., CCCH₂CH₂), 1.95−2.01 (1H,

Dimethyl (4-Fluorophenylamino)(2-(phenylethynyl)-

cyclohex-1-enyl)methylphosphonate (8c). Brownish solid, mp

158−159 °C. Yield 0.46 g, 56%. IR (KBr): υ_max3295 (NH), 2158

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.51−1.67 (4H, m, 2

× CH₂), 1.98−2.01 (1H, m, CHH), 2.32−2.35 (3H, m, CHH, CH₂),

m, CHH), 2.17−2.20 (2H, m, CH₂), 2.27 (1H, dd, J = 20.0; 4.0 Hz

3

3.80 (3H, d, J_H,P= 8.4 Hz, OCH₃), 3.83 (3H, d, J_H,P= 8.8 Hz,

OCH₃), 5.21 (1H, d, ²J_H,P= 25.6 Hz, CHNH), 6.63 (2H, dd, J = 13.2;

4.4 Hz, ArH), 6.88 (2H, t, J = 8.8 Hz, ArH), 7.33−7.36 (3H, m, ArH),

7.46−7.48 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.9

(CH₂), 22.0 (CH₂), 24.8 (d, ³J_C,P= 1.5 Hz, CH₂), 30.4 (d, ⁴J_C,P= 1.8

CHH), 2.40 (2H, t, J = 7.2 Hz, CCCH₂CH₂), 3.78 (3H, d, J_H,P

=

8.8 Hz, OCH₃), 3.80 (3H, d, ³J_H,P= 9.2 Hz, OCH₃), 5.21 (1H, d, ²J_H,P

= 26.0 Hz, CHNH), 6.66−6.69 (2H, m, ArH), 6.73 (1H, t, J = 7.6 Hz,

ArH), 7.16 (2H, dd, J = 8,4; 7.2 Hz, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 13.5 (CH₃), 21.6 (CH₂), 22.0 (CH₂, 2 × CH_2chex), 22.4

2

3

4

Hz, CH₂), 53.6 (d, J_C,P= 6.8 Hz, OCH₃), 53.7 (d, J_C,P= 7.1 Hz,

(CH₂), 24.4 (d, J_C,P= 1.5 Hz, CH₂), 30.8 (d, J_C,P= 1.9 Hz, CH₂),

1

4

2

OCH₃), 55.3 (d, J_C,P= 150.9 Hz, CH), 88.4 (d, J_C,P= 5.0 Hz, C_sp),

53.4 (d, J_C,P= 6.9 Hz, OCH₃), 53.7 (d, J_C,P= 7.0 Hz, OCH₃), 54.5

5

3

(d, ¹J_C,P= 150.9 Hz, CH), 80.0 (d, ⁴J_C,P= 4.9 Hz, C_sp), 95.5 (d, ⁵J_C,P

=

94.7 (d, J_C,P= 2.2 Hz, C_sp), 114.5 (d, J_C,F= 7.4 Hz, ArC), 115.7 (d,

2

3

2

J_C,F= 22.3 Hz, ArC), 121.2 (d, J_C,P= 12.4 Hz, C_sp), 123.2 (ArC),

2.0 Hz, C_sp), 113.6 (ArC), 118.2 (ArC), 121.5 (d, J_C,P= 12.6 Hz,

2

3

128.3 (ArC), 128.4 (ArC), 131.3 (ArC), 139.2 (d, ²J_C,P= 3.9 Hz, C_sp),

142.5 (dd, ³J_C,P= 16.7 Hz, ⁴J_C,F= 1.8 Hz, ArC), 156.3 (d, ¹J_C,F= 234.6

Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 436.1444.

C₂₃H₂₅FNNaO₃P requires 436.1448.

2

C_sp), 129.2 (ArC), 136.9 (d, J_C,P= 3.5 Hz, C_sp), 146.2 (d, J_C,P= 16.0

Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 384.1695.

C₂₀H₂₈NNaO₃P requires 384.1699.

Dimethyl (4-Methoxyphenylamino)(2-(pent-1-ynyl)-

cyclohex-1-enyl)methylphosphonate (8h). Brownish solid, mp

92−93 °C. Yield 0.51 g, 65%. IR (KBr): υ_max3308 (NH), 2216 (C

Dimethyl (4-Chlorophenylamino)(2-(phenylethynyl)-

cyclohex-1-enyl)methylphosphonate (8d). Yellowish solid, mp

139−140 °C. Yield 0.38 g, 44%. IR (KBr): υ_max3296 (NH), 2201

1

C) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.04 (3H, t, J = 7.2 Hz,

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.50−1.66 (4H, m, 2

CH₃), 1.41−1.55 (4H, m, 2 × CH₂), 1.61 (2H, sexst., J = 7.2 Hz, C

CCH₂CH₂), 1.92−1.98 (1H, m, CHH), 2.15−2.18 (2H, m, CH₂),

2.24−2.29 (1H, m, CHH), 2.39 (2H, t, J = 6.8 Hz, CCCH₂CH₂),

3.73 (3H, s, OCH₃), 3.77 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.80 (3H, d,

× CH₂), 1.98−1.99 (1H, m, CHH), 2.32−2.33 (3H, m, CHH, CH₂),

3

3.80 (3H, d, J_H,P= 6.4 Hz, OCH₃), 3.83 (3H, d, J_H,P= 6.4 Hz,

OCH₃), 5.22 (1H, d, ²J_H,P= 26.0 Hz, CHNH), 6.63 (2H, d, J = 8.8 Hz,

ArH), 7.11 (2H, d, J = 8.8 Hz, ArH), 7.33−7.35 (3H, m, ArH), 7.46−

7.48 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.9 (CH₂),

2

³J_H,P= 10.4 Hz, OCH₃), 5.14 (1H, d, J_H,P= 25.6 Hz, CHNH), 6.63

(2H, d, J = 9.2 Hz, ArH), 6.75 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ 13.5 (CH₃), 21.6 (CH₂), 22.0 (2 ×

CH_2chex), 22.4 (CH₂), 24.4 (d, ³J_C,P= 1.3 Hz, CH₂), 30.8 (d, ⁴J_C,P= 1.8

3

4

24.8 (d, J_C,P= 1.4 Hz, CH₂), 30.3 (d, J_C,P= 1.8 Hz, CH₂), 53.6 (d,

²J_C,P= 6.9 Hz, OCH₃), 53.7 (d, ²J_C,P= 7.1 Hz, OCH₃), 54.9 (d, ¹J_C,P

=

K

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

2

Hz, CH₂), 53.5 (d, J_C,P= 6.8 Hz, OCH₃), 53.6 (d, J_C,P= 7.0 Hz,

MHz, CDCl₃): δ 0.3 (CH(CH₂)₂), 8.8 (CH(CH₂)₂), 9.0 (CH-

(CH₂)₂), 22.0 (2 × CH₂), 24.5 (d, ³J_C,P= 1.6 Hz, CH₂), 30.6 (d, ⁴J_C,P

= 1.7 Hz, CH₂), 53.5 (d, ²J_C,P= 6.8 Hz, OCH₃), 53.7 (d, ²J_C,P= 7.1 Hz,

OCH₃), 55.3 (d, ¹J_C,P= 151.2 Hz, CH), 55.6 (OCH₃), 80.0 (d, ⁴J_C,P

4.9 Hz, C_sp), 95.4 (d, J_C,P= 2.1 Hz, C_sp), 114.7 (ArC), 115.0 (ArC),

=

5

3

2

1

4

2

121.6 (d, J_C,P= 12.7 Hz, C_sp), 136.9 (d, J_C,P= 3.4 Hz, C_sp), 140.1

OCH₃), 54.6 (d, J_C,P= 150.8 Hz, CH), 74.9 (d, J_C,P= 5.0 Hz, C_sp),

98.9 (d, ⁵J_C,P= 2.0 Hz, C_sp), 113.6 (ArC), 118.2 (ArC), 121.3 (d, ³J_C,P

(d, J_C,P= 16.5 Hz, ArC), 152.6 (ArC) ppm. HRMS (ESI): MNa⁺,

3

2

= 12.4 Hz, C_sp), 129.2 (ArC), 137.3 (d, J_C,P= 3.5 Hz, C_sp), 146.3 (d,

found 414.1811. C₂₁H₃₀NNaO₄P requires 414.1805.

Dimethyl (4-Fluorophenylamino)(2-(pent-1-ynyl)cyclohex-

1-enyl)methylphosphonate (8i). Brownish solid, mp 97−98 °C.

Yield 0.27 g, 35%. IR (KBr): υ_max3315 (NH), 2216 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 1.03 (3H, t, J = 7.2 Hz, CH₃), 1.45−1.63

(6H, 2m (overlap.), CCCH₂CH₂, 2 × CH₂), 1.89−1.94 (1H, m,

CHH), 2.15−2.18 (2H, m, CH₂), 2.26−2.28 (1H, m, CHH), 2.39

³J_C,P= 15.7 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 382.1542.

C₂₀H₂₆NNaO₃P requires 382.1543

Dimethyl (2-(Cyclopropylethynyl)cyclohex-1-enyl)(4-

methoxyphenylamino)methylphosphonate (8m). Yellowish

solid, mp 98−99 °C. Yield 0.45 g, 58%. IR (KBr): υ_max3306 (NH),

1

2213 (CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 0.72−0.76 (2H,

3

(2H, t, J = 7.2 Hz, CCCH₂CH₂), 3.77 (3H, d, J_H,P= 10.8 Hz,

m, CH(CH₂)₂), 0.85−0.89 (2H, m, CH(CH₂)₂), 1.41−1.58 (5H, m,

CH(CH₂)_2,2 × CH₂), 1.91−1.97 (1H, m, CHH), 2.13−2.16 (2H, m,

CH₂), 2.23−2.28 (1H, m, CHH), 3.74 (3H, s, OCH₃), 3.76 (3H, d,

OCH₃), 3.80 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 5.13 (1H, d, ²J_H,P= 25.6

Hz, CHNH), 6.59 (2H, dd, J = 8.8 Hz, ³J_H,F= 4.4 Hz, ArH), 6.86 (2H,

t, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.5 (CH₃),

3

³J_H,P= 10.4 Hz, OCH₃), 3.81 (3H, d, J_H,P= 10.8 Hz, OCH₃), 5.07

3

(1H, d, ²J_H,P= 25.6 Hz, CHNH), 6.60 (2H, d, J = 8.8 Hz, ArH), 6.76

(2H, d, J = 9.2 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 0.3

(CH(CH₂)₂), 8.8 (CH(CH₂)₂), 9.0 (CH(CH₂)₂), 22.0 (2 × CH₂),

21.5 (CH₂), 22.0 (2 × CH_2chex), 22.4 (CH₂), 24.3 (d, J_C,P= 1.4 Hz,

CH₂), 30.7 (d, J_C,P= 1.8 Hz, CH₂), 53.4 (d, J_C,P= 6.8 Hz, OCH₃),

53.7 (d, J_C,P= 7.0 Hz, OCH₃), 55.0 (d, J_C,P= 151.3 Hz, CH), 79.9

(d, J_C,P= 4.9 Hz, C_sp), 95.6 (d, J_C,P= 2.0 Hz, C_sp), 114.5 (d, J_C,F

4

2

1

4

5

3

4

2

=

24.5 (CH₂), 30.6 (d, J_C,P= 1.8 Hz, CH₂), 53.5 (d, J_C,P= 6.9 Hz,

2

3

2

1

7.3 Hz, ArC), 115.6 (d, J_C,F= 22.2 Hz), 121.9 (d, J_C,P= 12.6 Hz,

OCH₃), 53.6 (d, J_C,P= 7.0 Hz, OCH₃), 55.2 (d, J_C,P= 150.7 Hz,

C_sp), 136.5 (d, J_C,P= 3.5 Hz, C_sp), 142.4 (dd, J_C,P= 17.3 Hz, ⁴J_C,F

=

2

3

4

5

2

CH), 55.7 (OCH₃), 75.0 (d, J_C,P= 5.0 Hz, C_sp₃), 98.7 (d, J_C,P= 2.0

1

2

1.3 Hz, ArC), 156.2 (d, J_C,F= 234.4 Hz, ArC) ppm. HRMS (ESI):

Hz, C_sp), 114.7 (ArC), 114.8 (ArC), 121.3 (d, J_C,P= 12.5 Hz, C_sp),

MNa⁺, found 402.1598. C₂₀H₂₇FNNaO₃P requires 402.1605.

2

3

2

137.5 (d, J_C,P= 3.6 Hz, C_sp), 140.2 (d, J_C,P= 17.0 Hz, ArC), 152.5

(ArC) ppm. HRMS (ESI): MNa⁺, found 412.1640. C₂₁H₂₈NNaO₄P

requires 412.1648.

Dimethyl (2-(Hex-1-ynyl)cyclohex-1-enyl)(phenylamino)-

methylphosphonate (8j). Yellowish solid, mp 55−56 °C. Yield

0.37 g, 49%. IR (KBr): υ_max3514 (NH), 2214 (CC) cm⁻¹. ¹H NMR

(400 MHz, CDCl₃): δ 0.97 (3H, t, J = 7.2 Hz, CH₃), 1.46−1.60 (8H,

m, CCCH₂CH₂CH₂, 2 × CH₂), 1.96−2.01 (1H, m, CHH), 2.18−

2.19 (2H, m, CH₂), 2.25−2.30 (1H, m, CHH), 2.43 (2H, t, J = 6.4 Hz,

CCCH₂CH₂CH₂), 3.78 (3H, d, ³J_H,P= 9.6 Hz, OCH₃), 3.80 (3H, d,

Dimethyl (4-Chlorophenylamino)(2-(cyclopropylethynyl)-

cyclohex-1-enyl)methylphosphonate (8n). Brownish solid, mp

114−115 °C. Yield 0.44 g, 56%. IR (KBr): υ_max3295 (NH), 2212

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 0.71−0.75 (2H, m,

CH(CH₂)₂), 0.86−0.89 (2H, m, CH(CH₂)₂), 1.41−1.47 (1H, m,

CH(CH₂)₂), 1.49−1.56 (3H, m, CH₂), 1.88−1.93 (1H, m, CHH),

2.13−2.16 (2H, m, CH₂), 2.19−2.26 (1H, m, CHH), 3.76 (3H, d, ³J_H,P

= 10.4 Hz, OCH₃), 3.80 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 5.07 (1H, d,

²J_H,P= 25.6 Hz, CHNH), 6.57 (2H, d, J = 9.2 Hz, ArH), 7.10 (2H, d, J

= 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 0.3

(CH(CH₂)₂), 8.8 (CH(CH₂)₂), 9.0 (CH(CH₂)₂), 22.0 (2 × CH₂),

³J_H,P= 9.6 Hz, OCH₃), 5.20 (1H, d, J_H,P= 25.6 Hz, CHNH), 6.68

2

(2H, dd, J = 8.4; 0.8 Hz, ArH), 6.73 (1H, tt, J = 7.6; 1.2 Hz, ArH), 7.16

(2H, dd, J = 8,4; 7.2 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

13.6 (CH₃), 19.2 (CH₂), 22.0 (CH₂, 2 × CH_2chex), 24.4 (d, ³J_C,P= 1.5

4

2

Hz, CH₂), 30.8 (d, J_C,P= 1.8 Hz, CH₂), 31.0 (CH₂), 53.4 (d, J_C,P

=

6.9 Hz, OCH₃), 53.7 (d, ²J_C,P= 7.2 Hz, OCH₃), 54.6 (d, ¹J_C,P= 150.7

4

5

3

4

Hz, CH), 79.9 (d, J_C,P= 4.8 Hz, C_sp), 95.6 (d, J_C,P= 2.0 Hz, C_sp),

113.6 (ArC), 118.2 (ArC), 121.5 (d, J_C,P= 12.6 Hz, C_sp), 129.2

(ArC), 136.8 (d, J_C,P= 3.6 Hz, C_sp), 146.2 (d, J_C,P= 16.0 Hz, ArC)

ppm. HRMS (ESI): MNa⁺, found 398.1858. C₂₁H₃₀NNaO₃P requires

398.1856.

24.5 (d, J_C,P= 1.4 Hz, CH₂), 30.6 (d, J_C,P= 1.8 Hz, CH₂), 53.4 (d,

3

²J_C,P= 6.9 Hz, OCH₃), 53.7 (d, ²J_C,P= 7.0 Hz, OCH₃), 54.6 (d, ¹J_C,P

=

2

3

4

5

2

151.1 Hz, CH), 74.8 (d, J_C,P= 4.9 Hz, C_sp), 99.1 (d, J_C,P= 2.0 Hz,

C_sp), 114.7 (ArC), 121.7 (d, ³J_C,P= 12.5 Hz, C_sp), 122.9 (ArC), 129.0

2

(ArC), 136.7 (d, ²J_C,P= 3.9 Hz, C_sp), 144.9 (d, J_C,P= 16.3 Hz, ArC)

3

2

ppm. HRMS (ESI): MNa⁺, found 416.1150. C₂₀H₂₅ClNNaO₃P

requires 416.1153.

D i m e t h y l ( 2 - ( H e x - 1 - y n y l ) c y c l o h e x - 1 - e n y l ) ( 4 -

methoxyphenylamino)methylphosphonate (8k). Light brown

solid, mp 72−71 °C. Yield 0.45 g, 56%. IR (KBr): υ_max3307 (NH),

Dimethyl (4-Chlorophenylamino)(2-(p-tolylethynyl)-

cyclohex-1-enyl)methylphosphonate (8o). Yellowish solid, mp

112−113 °C. Yield 0.47 g, 53%. IR (KBr): υ_max3309 (NH), 2118

1

2213 (CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 0.93 (3H, t, J =

7.2 Hz, CH₃), 1.43−1.60 (8H, m, CCCH₂CH₂CH₂, 2 × CH₂),

1.93−1.98 (1H, m, CHH), 2.14−2.17 (2H, m, CH₂), 2.24−2.29 (1H,

m, CHH), 2.41 (2H, t, J = 6.4 Hz, CCCH₂CH₂CH₂), 3.73 (3H, s,

OCH₃), 3.77 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.80 (3H, d, ³J_H,P= 10.4

Hz, OCH₃), 5.13 (1H, d, ²J_H,P= 25.6 Hz, CHNH), 6.63 (2H, d, J = 9.2

Hz, ArH), 6.75 (2H, d, J = 9.2 Hz, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 13.6 (CH₃), 19.2 (CH₂), 21.9 (CH₂), 22.0 (2 × CH_2chex),

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.52−1.65 (4H, m, 2

× CH₂), 1.97−2.03 (1H, m, CHH), 2.31−2.34 (3H, m, CHH, CH₂),

3

2.36 (3H, s, CH₃), 3.79 (3H, d, J_H,P= 6.0 Hz, OCH₃), 3.82 (3H, d,

2

³J_H,P= 6.0 Hz, OCH₃), 5.22 (1H, d, J_H,P= 25.6 Hz, CHNH), 6.63

(2H, d, J = 8.8 Hz, ArH), 7.11 (2H, d, J = 8.8 Hz, ArH), 7.15 (2H, d, J

= 7.6 Hz, ArH), 7.36 (2H, d, J = 8.0 Hz, ArH) ppm. ¹³C NMR (100

3

4

MHz, CDCl₃): δ 21.4 (CH₃), 21.9 (CH₂), 22.0 (CH₂), 24.7 (d, ³J_C,P

1.4 Hz, CH₂), 30.3 (d, J_C,P= 1.7 Hz, CH₂), 53.6 (d, J_C,P= 6.9 Hz,

=

24.4 (d, J_C,P= 1.4 Hz, CH₂), 30.8 (d, J_C,P= 1.8 Hz, CH₂), 31.0

(CH₂), 53.5 (d, ²J_C,P= 6.8 Hz, OCH₃), 53.6 (d, ²J_C,P= 7.1 Hz, OCH₃),

55.3 (d, ¹J_C,P= 151.1 Hz, CH), 55.6 (OCH₃), 79.9 (d, ⁴J_C,P= 4.9 Hz,

C_sp), 95.5 (d, ⁵J_C,P= 2.0 Hz, C_sp), 114.7 (ArC), 114.9 (ArC), 121.6 (d,

4

2

1

OCH₃), 53.8 (d, J_C,P= 7.2 Hz, OCH₃), 54.9 (d, J_C,P= 150.9 Hz,

CH), 87.7 (d, ⁴J_C,P= 5.1 Hz, C_sp), 95.0 (d, ⁵J_C,P= 2.2 Hz, C_sp), 114.7

3

2

3

2

J_C,P= 12.6 Hz, C_sp), 136.9 (d, J_C,P= 3.4 Hz, C_sp), 140.1 (d, J_C,P

=

(ArC), 120.0 (ArC), 121.4 (d, J_C,P= 12.4 Hz, C_sp), 123.0 (ArC),

16.9 Hz, ArC), 152.6 (ArC) ppm. HRMS (ESI): MNa⁺, found

428.1953. C₂₂H₃₂NNaO₄P requires 428.1961.

129.1 (ArC), 129.2 (ArC), 131.1 (ArC), 138.4 (d, ²J_C,P= 4.0 Hz, C_sp),

2

3

138.5 (ArC), 144.9 (d, J_C,P= 16.3 Hz, ArC) ppm. HRMS (ESI):

MNa⁺, found 466.1307. C₂₄H₂₇ClNNaO₃P requires 466.1309.

Dimethyl (Phenylamino)(2-(phenylethynyl)phenyl)-

methylphosphonate (9a). White solid, mp 154−155 °C. Yield

0.34 g, 44%. IR (KBr): υ_max3348 (NH), 2212 (CC) cm⁻¹. ¹H NMR

(400 MHz, CDCl₃): δ 3.44 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.85 (3H,

Dimethyl (2-(Cyclopropylethynyl)cyclohex-1-enyl)-

(phenylamino)methylphosphonate (8l). Yellowish solid, mp

125−124 °C. Yield 0.26 g, 36%. IR (KBr): υ_max3308 (NH), 2207

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 0.74−0.77 (2H, m,

1

CH(CH₂)₂), 0.85−0.89 (2H, m, CH(CH₂)₂), 1.51−1.58 (5H, m,

CH(CH₂)_2,2 × CH₂), 1.95−2.00 (1H, m, CHH), 2.15−2.17 (2H, m,

3

2

d, J_H,P= 10.8 Hz, OCH₃), 5.59 (1H, d, J_H,P= 24.4 Hz, CHNH),

6.67−6.72 (3H, m, ArH), 7.09−7.13 (2H, m, ArH), 7.25- 7.35 (2H, m,

ArH), 7.38−7.41 (3H, m, ArH), 7.57−7.64 (4H, m, ArH) ppm. ¹³C

3

CH₂), 2.21−2.28 (1H, m, CHH), 3.77 (3H, d, J_H,P= 10.8 Hz,

OCH₃), 3.81 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 5.14 (1H, d, ²J_H,P= 25.6

Hz, CHNH), 6.65 (2H, d, J = 7.6 Hz, ArH), 6.74 (1H, t, J = 7.6 Hz,

ArH), 7.33−7.35 (2H, dd, J = 8.4; 7.6 Hz, ArH) ppm. ¹³C NMR (100

1

NMR (100 MHz, CDCl₃): δ 52.9 (d, J_C,P= 151.0 Hz, CH), 53.8 (d,

²J_C,P= 6.3 Hz, OCH₃), 53.9 (d, ²J_C,P= 6.2 Hz, OCH₃), 86.8 (d, ⁴J_C,P

=

L

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

2.0 Hz, C_sp), 95.1 (C_sp), 113.8 (ArC), 118.6 (ArC), 122.9 (ArC),

C_sp), 110.1 (ArC), 114.1 (2 × ArC), 114.9 (d, J = 1.6 Hz, ArC), 118.4

3

123.2 (d, ³J_C,P= 8.7 Hz, ArC), 127.4 (d, ³J_C,P= 4.4 Hz, ArC), 127.9 (d,

(ArC), 120.7 (ArC), 121.7 (d, J_C,P= 10.1 Hz, ArC), 122.1 (ArC),

2

4

⁵J_C,P= 3.1 Hz, ArC), 128.5 (ArC), 128.7 (ArC), 129.0 (d, J_C,P= 3.1

123.7 (ArC), 125.9 (d, J_C,P= 3.0 Hz, ArC), 126.5 (ArC), 127.4

4

(ArC), 128.5 (ArC), 128.6 (ArC), 128.9 (ArC), 129.0 (ArC), 131.4

Hz, ArC), 129.2 (ArC), 131.5 (ArC), 132.2 (d, J_C,P= 2.1 Hz, ArC),

3

2

3

(ArC), 136.9 (ArC), 137.3 (ArC), 146.3 (d, J_C,P= 14.9 Hz, ArC)

137.7 (d, J_C,P= 1.8 Hz, ArC), 145.7 (d, J_C,P= 14.8 Hz, ArC) ppm.

HRMS (ESI): MNa⁺, found 414.1228. C₂₃H₂₂NNaO₃P requires

414.1230.

ppm. HRMS (ESI): MNa⁺, found 543.1807. C₃₂H₂₉N₂NaO₃P requires

543.1808.

Dimethyl (1-Benzyl-2-(hex-1-ynyl)-1H-indol-3-yl)(4-

methoxyphenylamino)methylphosphonate (19b). Yellowish

solid, mp 132−133 °C. Yield 0.24 g, 46%. IR (KBr): υ_max3480

(NH), 2214 (CC) cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 0.93 (3H,

t, J = 7.2 Hz, CH₃), 1.46 (2H, sext., J = 7.2 Hz, CCCH₂CH₂CH₂),

1.58−1.65 (2H, m, CCCH₂CH₂CH₂), 2.55 (2H, t, J = 7.2 Hz, C

OCH₃), 3.85 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 5.25 (1H, d, ²J_H,P= 24.0

Hz, CHNH), 5.37 (2H, s, NCH₂), 6.53−6.72 (4H, m, ArH), 6.96−

6.98 (2H, m, ArH), 7.11- 7.12 (3H, m, ArH), 7.20−7.21 (3H, m,

ArH), 7.94−7.97 (1H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

13.6 (CH₃), 19.5 (CH₂), 21.9 (CH₂), 30.6 (CH₂), 47.8 (NCH₂), 50.5

Dimethyl (4-Chlorophenylamino)(2-(phenylethynyl)phenyl)-

methylphosphonate (9b). Yellowish solid, mp 149−150 °C.

Yield0.51 g, 60%. IR (KBr): υ_max3508 (NH), 2213 (CC) cm⁻¹.

¹H NMR (400 MHz, CDCl₃): δ 3.44 (3H, d, ³J_H,P= 10.4 Hz, OCH₃),

3.85 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 4.44 (1H, br. s, NH), 5.53 (1H,

d, ²J_H,P= 24.4 Hz, CHNH), 6.59 (2H, d, J = 8.8 Hz, ArH), 7.05 (2H,

d, J = 8.8 Hz, ArH), 7.28−7.35 (2H, m, ArH), 7.38−7.40 (3H, m,

ArH), 7.57−7.61 (4H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

3

CCH₂CH₂CH₂), 3.46 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.68 (3H, s,

1

2

53.0 (d, J_C,P= 151.5 Hz, CH), 53.8 (d, J_C,P= 6.9 Hz, OCH₃), 53.9

2

4

(d, J_C,P= 7.0 Hz, OCH₃), 86.7 (d, J_C,P= 2.0 Hz, C_sp), 95.3 (C_sp),

114.9 (ArC), 122.8 (ArC), 123.2 (ArC), 123.2 (d, J_C,P= 7.0 Hz,

ArC), 127.3 (d, J_C,P= 4.3 Hz, ArC), 128.0 (d, J_C,P= 3.0 Hz, ArC),

128.5 (ArC), 128.8 (ArC), 129.0 (d, J_C,P= 3.1 Hz, ArC), 129.1

6

3

5

1

2

4

(d, J_C,P= 161.0 Hz, CH), 53.6 (d, J_C,P= 5.4 Hz, OCH₃), 53.7 (d,

²J_C,P= 5.5 Hz, OCH₃), 55.6 (OCH₃), 71.1 (d, J_C,P= 3.2 Hz, C_sp),

4

2

(ArC), 131.5 (ArC), 132.3 (d, J_C,P= 2.2 Hz, ArC), 137.2 (d, J_C,P

=

101.1 (d, ⁵J_C,P= 1.4 Hz, C_sp), 109.9 (ArC), 113.4 (ArC), 114.5 (ArC),

3

2.1 Hz, ArC), 144.4 (d, J_C,P= 15.1 Hz, ArC) ppm. HRMS (ESI):

MNa⁺, found 448.0836. C₂₃H₂₁ClNNaO₃P requires 448.0840.

Dimethyl (4-Methoxyphenylamino)(2-((trimethylsilyl)-

ethynyl)phenyl)methylphosphonate (9c-TMS). Yellowish solid,

mp 115−116 °C. Yield 0.59 g, 71%. IR (KBr): υ_max2157 (CC),

3287 (NH) cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 0.30 (9H, s, CH₃),

3.43 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 3.68 (3H, s, OCH₃), 3.84 (3H, d,

3

115.8 (ArC), 120.4 (ArC), 120.6 (ArC), 122.9 (d, J_C,P= 10.5 Hz,

ArC), 123.1 (ArC), 125.8 (d, ²J_C,P= 2.7 Hz, ArC), 126.3 (ArC), 127.2

3

(ArC), 128.5 (ArC), 136.4 (ArC), 137.5 (ArC), 140.3 (d, J_C,P= 15.9

Hz, ArC), 152.8 (ArC) ppm. HRMS (ESI): MNa⁺, found 553.2218.

C₃₁H₃₅N₂NaO₄P requires 553.2227.

Dimethyl (1-Benzyl-2-(cyclopropylethynyl)-1H-indol-3-yl)-

(phenylamino)methylphosphonate (19c). Yellowish solid, mp

106−107 °C. Yield 0.31 g, 32%. IR (KBr): υ_max3314 (NH), 2219

2

³J_H,P= 10.4 Hz, OCH₃), 5.46 (1H, d, J_H,P= 24.8 Hz, CHNH), 6.62

(2H, d, J = 8.8 Hz, ArH), 6.70 (2H, d, J = 9.2 Hz, ArH), 7.20 (1H, tt, J

= 7.6 Hz; 1.6 Hz, ArH), 7.30 (1H, t, J = 7.6 Hz, ArH), 7.47 (1H, d, J =

7.6 Hz, ArH), 7.58 (1H, d, J = 7.2 Hz, ArH) ppm. ¹³C NMR (100

1

(CC) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 1.16−1.19 (2H, m,

CH(CH₂)₂), 1.29−1.32 (2H, m, CH(CH₂)₂), 1.89−1.95 (1H, m,

CH(CH₂)₂), 3.78 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 4.18 (3H, d, ³J_H,P

=

1

MHz, CDCl₃): δ 0.1 (CH₃), 53.4 (d, J_C,P= 150.2 Hz, CH), 53.7 (d,

2

²J_C,P= 6.1 Hz, OCH₃), 53.8 (d, ²J_C,P= 6.2 Hz, OCH₃), 55.6 (OCH₃),

10.8 Hz, OCH₃), 5.65 (1H, d, J_H,P= 24.4 Hz, CHNH), 5.70 (2H, s,

NCH₂), 7.03 (1H, t, J = 7.2 Hz, ArH), 7.08 (2H, d, J = 8.0 Hz, ArH),

7.34- 7.57 (10H, m, ArH), 8.27−8.29 (1H, m, ArH) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ 0.5 (CH(CH₂)₂), 9.3 (2 × CH(CH₂)₂), 47.8

3

100.3 (C_sp), 102.7 (C_sp), 114.7 (ArC), 115.2 (ArC), 123.2 (d, J_C,P

=

5

7.5 Hz, ArC), 127.4 (ArC), 127.7 (d, J_C,P= 2.4 Hz, ArC), 129.2 (d,

⁴J_C,P= 3.0 Hz, ArC), 132.3 (d, J_C,P= 1.9 Hz, ArC), 138.1 (ArC),

4

1

2

(NCH₂), 49.3 (d, J_C,P= 160.7 Hz, CH), 53.6 (d, J_C,P= 6.9 Hz,

139.4 (ArC), 152.9 (ArC) ppm. HRMS (ES): MNa⁺, found 440.1419.

C₂₁H₂₈NNaO₄PSi requires 440.1417.

2

4

OCH₃), 53.7 (d, J_C,P= 6.9 Hz, OCH₃), 65.8 (d, J_C,P= 3.3 Hz, C_sp),

104.5 (d, J_C,P= 1.1 Hz, C_sp), 110.0 (ArC), 113.8 (ArC), 114.1 (2 ×

ArC), 118.4 (ArC), 120.4 (ArC), 122.6 (d, J_C,P= 10.4 Hz, ArC),

4

Dimethyl (2-Ethynylphenyl)(4-methoxyphenylamino)-

methylphosphonate (9c). This compound was synthesized from

9c-TMS by treating with 2 equiv of KF₂·H₂O in methanol at room

temperature for 2 h. After evaporation of solvent, the residue was

puriﬁed by column chromatography. White solid, mp 171−172 °C.

Yield 0.38 g, 78%. IR (KBr): υ_max3504 (NH), 2101 (CC) cm⁻¹. ¹H

NMR (400 MHz, CDCl₃): δ 3.44 (4H, d and s (overlap.), ³J_H,P= 10.8

3

2

123.2 (ArC), 125.8 (d, J_C,P= 2.8 Hz, ArC), 126.4 (ArC), 127.3

(ArC), 128.5 (ArC), 128.9 (ArC), 136.4 (ArC), 137.5 (ArC), 146.4

(d, ³J_C,P= 15.0 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 507.1793.

C₂₉H₂₉N₂NaO₃P requires 507.1808.

General Procedure for the Preparation of Compounds 10

and 14. To a solution of the corresponding acetylenic α-

anilinomethylphosphonate 7 were added 8 (1 mmol) in dry

chloroform (5 mL) and potassium tert-butanoate (0.112 g, 1 mmol),

together with gold(III) bromide (43.7 mg, 0.1 mmol). The resulting

solution was stirred at room temperature. When the completion of the

reaction was observed by TLC (after 0.5−2 h), the solution was

evaporated under reduced pressure, and the residue was puriﬁed by

ﬂash column chromatography eluting with hexane−ethyl acetate

mixtures.

3

Hz, OCH₃, CH), 3.68 (3H, s, OCH₃), 3.85 (3H, d, J_H,P= 10.8 Hz,

OCH₃), 5.44 (1H, d, ²J_H,P= 24.0 Hz, CHNH), 6.64 (2H, d, J = 8.8 Hz,

ArH), 6.69 (2H, d, J = 9.2 Hz, ArH), 7.24 (1H, tt, J = 7.6 Hz; 1.6 Hz,

ArH), 7.34 (1H, t, J = 7.2 Hz, ArH), 7.52 (1H, d, J = 7.6 Hz, ArH),

7.63 (1H, d, J = 7.6 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

1

2

53.7 (d, J_C,P= 151.1 Hz, CH), 53.8 (d, J_C,P= 7.0 Hz, OCH₃), 54.0

(d, ²J_C,P= 6.8 Hz, OCH₃), 55.6 (OCH₃), 81.2 (d, ⁴J_C,P= 1.9 Hz, C_sp),

3

82.8 (C_sp), 114.7 (ArC), 115.7 (ArC), 122.2 (d, J_C,P= 7.2 Hz, ArC),

127.5 (d, ³J_C,P= 4.2 Hz, ArC), 127.9 (d, ⁵J_C,P= 3.0 Hz, ArC), 129.5 (d,

Dimethyl 3-Benzyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

[c]pyrrol-1-ylphosphonate (10a). Yellowish oil. Yield 0.37 g,

98%. ¹H NMR (400 MHz, CDCl₃): δ 2.24−2.32 (2H, m,

CH₂CH₂CH₂), 2.35−2.38 (2H, m, CH₂CH₂CH₂), 2.84−2.87 (2H,

m, CH₂CH₂CH₂), 3.42 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.65 (2H,

br. s, CH₂), 6.91−6.93 (2H, m, ArH), 7.12−7.21 (5H, m, ArH), 7.35−

7.39 (3H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 24.8 (CH₂),

26.6 (CH₂), 30.3 (CH₂), 32.3 (CH₂), 52.0 (d, ²J_C,P= 5.6 Hz, OCH₃),

⁴J_C,P= 3.0 Hz, ArC), 132.9 (d, J_C,P= 2.1 Hz, ArC), 138.0 (ArC),

4

6

138.9 (ArC), 153.2 (d, J_C,P= 1.2 Hz, ArC) ppm. HRMS (ESI):

MNa⁺, found 368.1022. C₁₈H₂₀NNaO₄P requires 368.1022.

Dimethyl (1-Benzyl-2-(phenylethynyl)-1H-indol-3-yl)-

(phenylamino)methylphosphonate (19a). Yellowish solid,

mp156−157 °C. Yield 0.44 g, 42%. IR (KBr): υ_max3316 (NH),

2214 (CC) cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 3.50 (3H, d, ³J_H,P

= 10.4 Hz, OCH₃), 3.88 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 5.47 (1H, d,

²J_H,P= 24.4 Hz, CHNH), 5.47 (2H, s, NCH₂), 6.71 (1H, t, J = 7.2 Hz,

1

110.2 (d, J_C,P= 234.2 Hz, C-sp²), 126.0 (ArC), 128.1 (ArC), 128.3

3

(ArC), 128.3 (ArC), 128.5 (ArC), 128.8 (ArC), 129.4 (d, J_C,P= 14.2

Hz, C-sp²), 131.5 (d, ⁴J_C,P= 8.5 Hz, C-sp²), 138.5 (ArC), 138.7 (ArC),

ArH), 6.81 (2H, d, J = 8.0 Hz, ArH), 7.09- 7.26 (10H, m, ArH), 7.40−

7.41 (3H, m, ArH), 7.55−7.58 (2H, m, ArH), 8.03 (1H, d, J = 6.4 Hz,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 48.0 (NCH₂), 49.4 (d,

2

144.5 (d, J_C,P= 17.4 Hz, C-sp²) ppm. HRMS (ESI): MNa⁺, found

404.1388. C₂₂H₂₄NNaO₃P requires 404.1386.

Dimethyl 3-Benzyl-2-(4-methoxyphenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10b). Yellow-

¹J_C,P= 160.2 Hz, CH), 53.6 (d, ²J_C,P= 7.0 Hz, OCH₃), 53.7 (d, ²J_C,P

7.0 Hz, OCH₃), 79.6 (d, J_C,P= 3.5 Hz, C_sp), 99.6 (d, J_C,P= 1.5 Hz,

=

4

5

M

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

1

ish oil. Yield 0.30 g, 74%. H NMR (400 MHz, CDCl₃): δ 2.23−2.30

Dimethyl 2-(4-Methoxyphenyl)-3-(4-methylbenzyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10 g). Yellow-

(2H, m, CH₂CH₂CH₂), 2.34−2.37 (2H, m, CH₂CH₂CH₂), 2.82−2.86

(2H, m, CH₂CH₂CH₂), 3.51 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.63

(2H, br. s, CH₂), 3.82 (3H, s, OCH₃), 6.86 (2H, d, ³J = 9.2 Hz, ArH),

6.92−6.94 (2H, m, ArH), 7. Ten (2H, d, J = 9.2 Hz, ArH), 7.14−7.21

(3H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 24.8 (CH₂), 26.6

(CH₂), 30.3 (CH₂), 32.3 (CH₂), 52.1 (d, ²J_C,P= 5.5 Hz, OCH₃), 55.3

1

ish oil. Yield 0.32 g, 76%. H NMR (400 MHz, CDCl₃): δ 2.25−2.30

(5H, m, CH₂CH₂CH₂and CH₃), 2.33−2.37 (2H, m, CH₂CH₂CH₂),

3

2.81−2.85 (2H, m, CH₂CH₂CH₂), 3.51 (6H, d, J_H,P= 11.2 Hz, 2 ×

OCH₃), 3.58 (2H, br. s, CH₂), 3.83 (3H, s, OCH₃), 6.83 (2H, d, ³J =

8.0 Hz, ArH), 6.87 (2H, d, ³J = 8.8 Hz, ArH), 7.01 (2H, d, ³J = 8.0 Hz,

3

ArH), 7.12 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

(OCH₃), 110.1 (d, J_C,P= 234.7 Hz, C-sp²), 113.4 (ArC), 126.0

1

(ArC), 128.1 (ArC), 128.6 (ArC), 129.1 (d, J_C,P= 14.2 Hz, C-sp²),

3

CDCl₃): δ 20.9 (CH₃), 24.9 (CH₂), 26.6 (CH₂), 30.3 (CH₂), 31.8

(CH₂), 52.1 (d, ²J_C,P= 5.5 Hz, OCH₃), 55.3 (OCH₃), 110.0 (d, ¹J_C,P

=

129.8 (ArC), 131.5 (ArC), 131.9 (d, J_C,P= 8.5 Hz, C-sp²), 138.6

4

234.3 Hz, C-sp²), 113.4 (ArC), 128.5 (ArC), 128.8 (ArC), 128.9

(ArC), 144.2 (d, J_C,P= 17.5 Hz, C-sp²), 159.2 (ArC) ppm. HRMS

2

4

(ESI): MNa⁺, found 434.1497. C₂₃H₂₆NNaO₄P requires 434.1492.

Dimethyl 3-Benzyl-2-(4-ethoxyphenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10c). Yellow-

ish oil. Yield 0.32 g, 76%. ¹H NMR (400 MHz, CDCl₃): δ 1.42 (3H, t,

³J = 6.8 Hz, OCH₂CH₃), 2.23−2.31 (2H, m, CH₂CH₂CH₂), 2.34−

(ArC), 129.1 (ArC), 129.8 (ArC), 131.5 (ArC), 132.1 (d, J_C,P= 8.5

2

Hz, C-sp²), 135.5 (ArC), 144.3 (d, J_C,P= 17.6 Hz, C-sp²), 159.2

(ArC) ppm. HRMS (ESI): MNa⁺, found 448.1643. C₂₄H₂₈NNaO₄P

requires 448.1648.

Dimethyl 3-(4-Ethylbenzyl)-2-(4-methoxyphenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10h). Yellow-

ish oil. Yield 0.42 g, 96%. ¹H NMR (400 MHz, CDCl₃): δ 1.19 (3H, t,

³J = 7.6 Hz, CH₃), 2.23−2.30 (2H, m, CH₂CH₂CH₂), 2.35−2.38 (2H,

2.37 (2H, m, CH₂CH₂CH₂), 2.82−2.86 (2H, m, CH₂CH₂CH₂), 3.50

(6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.63 (2H, br. s, CH₂), 4.04 (2H,

q, ³J = 6.8 Hz, OCH₂CH₃), 6.85 (2H, d, ³J = 8.8 Hz, ArH), 6.93−6.95

3

m, CH₂CH₂CH₂), 2.58 (2H, q, J = 7.6 Hz, CH₂CH₃), 2.81−2.85

3

(2H, m, ArH), 7. Ten (2H, d, J = 8.8 Hz, ArH), 7.14−7.21 (3H, m,

(2H, m, CH₂CH₂CH₂), 3.50 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.59

(2H, br. s, CH₂), 3.83 (3H, s, OCH₃), 6.84−6.87 (4H, m, ArH), 7.03

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 14.7 (CH₃), 24.8 (CH₂),

26.6 (CH₂), 30.3 (CH₂), 32.3 (CH₂), 52.0 (d, ²J_C,P= 5.5 Hz, OCH₃),

3

(2H, d, J = 8.4 Hz, ArH), 7.11 (2H, d, J = 9.2 Hz, ArH) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ 15.6 (CH₃), 24.8 (CH₂), 26.6 (CH₂),

28.3 (CH₂), 30.3 (CH₂), 31.8 (CH₂), 52.1 (d, ²J_C,P= 5.5 Hz, OCH₃),

63.5 (OCH₂CH₃), 110.2 (d, J_C,P= 234.4 Hz, C-sp²), 113.9 (ArC),

1

3

126.0 (ArC), 128.1 (ArC), 128.6 (ArC), 129.0 (d, J_C,P= 14.3 Hz, C-

sp²), 129.8 (ArC), 131.3 (ArC), 131.8 (d, ⁴J_C,P= 8.6 Hz, C-sp²), 138.6

55.3 (OCH₃), 109.8 (d, J_C,P= 235.1 Hz, C-sp²), 113.4 (ArC), 127.6

1

(ArC), 144.2 (d, J_C,P= 17.5 Hz, C-sp²), 158.6 (ArC) ppm. HRMS

2

(ArC), 128.5 (ArC), 129.0 (d, J_C,P= 14.2 Hz, C-sp²), 129.8 (ArC),

3

(ESI): MNa⁺, found 448.1649. C₂₄H₂₈NNaO₄P requires 448.1648.

Dimethyl 3-Benzyl-2-(4-ﬂuorophenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10d). Yellow-

131.5 (ArC), 132.3 (d, J_C,P= 8.6 Hz, C-sp²), 135.8 (ArC), 141.9

4

(ArC), 144.4 (d, J_C,P= 17.5 Hz, C-sp²), 159.2 (ArC) ppm. HRMS

2

(ESI): MNa⁺, found 462.1808. C₂₅H₃₀NNaO₄P requires 462.1805.

Dimethyl 3-Pentyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

[c]pyrrol-1-ylphosphonate (10i). Yellowish oil. Yield 0.31 g, 86%.

¹H NMR (400 MHz, CDCl₃): δ 0.79 (3H, t, ³J = 7.2 Hz,

1

ish oil. Yield 0.32 g, 86%. H NMR (400 MHz, CDCl₃): δ 2.25−2.33

(2H, m, CH₂CH₂CH₂), 2.38−2.41 (2H, m, CH₂CH₂CH₂), 2.82−2.86

(2H, m, CH₂CH₂CH₂), 3.52 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.64

(2H, br. s, CH₂), 6.89−6.91 (2H, m, ArH), 7.01−7.05 (2H, m, ArH),

7.12−7.21 (5H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 24.8

CH₂(CH₂)₃CH₃), 1.09−1.21 (4H, m, CH₂CH₂(CH₂)₂CH₃), 1.42

3

(2H, quint, J = 7.6 Hz, CH₂CH₂(CH₂)₂CH₃), 2.27 (2H, t, J = 7.6

2

(CH₂), 26.6 (CH₂), 30.4 (CH₂), 32.3 (CH₂), 52.1 (d, J_C,P= 5.6 Hz,

Hz, CH₂CH₂(CH₂)₂CH₃), 2.36 (2H, quint, ³J = 7.2 Hz,

CH₂CH₂CH₂), 2.65 (2H, t, J = 7.2 Hz, CH₂CH₂CH₂), 2.84 (2H,

td, J_HH= 6.8 Hz, J_HP= 1.2 Hz, CH₂CH₂CH₂), 3.48 (6H, d, J_H,P

OCH₃), 110.4 (d, J_C,P= 234.6 Hz, C-sp²), 115.2 (d, J_C,F= 22.6 Hz,

3

1

3

4

3

ArC), 126.1 (ArC), 128.2 (ArC), 128.5 (ArC), 129.6 (d, J_C,P= 14.2

=

Hz, C-sp²), 130.5 (d, ³J_C,F= 8.7 Hz, ArC), 131.7 (d, ⁴J_C,P= 8.4 Hz, C-

sp²), 134.7 (d, ⁴J_C,F= 3.1 Hz, ArC), 138.4 (ArC), 144.5 (d, ²J_C,P= 17.3

11.2 Hz, 2 × OCH₃), 7.26−7.28 (2H, m, ArH), 7.39−7.44 (3H, m,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.8 (CH₃), 22.1 (CH₂),

25.1 (CH₂), 26.0 (CH₂), 26.5 (CH₂), 27.8 (CH₂), 30.4 (CH₂), 31.3

(CH₂), 51.9 (d, ²J_C,P= 5.5 Hz, OCH₃), 109.3 (d, ¹J_C,P= 234.8 Hz, C-

Hz, C-sp²), 162.2 (d, J_C,F= 246.6 Hz, ArH) ppm. HRMS (ESI):

1

MH⁺, found 400.1473. C₂₂H₂₄FNO₃P requires 400.1472.

3

sp²), 128.0 (d, J_C,P= 14.4 Hz, C-sp²), 128.2 (ArC), 128.3 (ArC),

Dimethyl 3-Benzyl-2-(4-chlorophenyl)-2,4,5,6-

4

128.6 (ArC), 133.6 (d, J_C,P= 8.4 Hz, C-sp²), 138.9 (ArC), 144.6 (d,

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10e). Yellow-

1

²J_C,P= 17.5 Hz, C-sp²) ppm. HRMS (ESI): MNa⁺, found 384.1697.

ish oil. Yield 0.3 g, 73%. H NMR (400 MHz, CDCl₃): δ 2.25−2.32

(2H, m, CH₂CH₂CH₂), 2.37−2.40 (2H, m, CH₂CH₂CH₂), 2.82−2.86

C₂₀H₂₈NNaO₃P requires 384.1699.

(2H, m, CH₂CH₂CH₂), 3.52 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.64

Dimethyl 2-(4-Methoxyphenyl)-3-pentyl-2,4,5,6-

3

(2H, br. s, CH₂), 6.90−6.92 (2H, m, ArH), 7. Eleven (2H, d, J = 8.8

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10j). Yellow-

3

1

Hz, ArH), 7.15−7.22 (3H, m, ArH), 7.32 (2H, d, J = 8.8 Hz, ArH)

ish oil. Yield 0.3 g, 78%. H NMR (400 MHz, CDCl₃): δ 0.80 (3H, t,

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 24.8 (CH₂), 26.6 (CH₂), 30.4

³J

=

6.8 Hz, CH₂(CH₂)₃CH₃), 1.13−1.22 (4H, m,

CH₂CH₂(CH₂)₂CH₃), 1.42 (2H, quint, ³J

7.6 Hz,

CH₂CH₂(CH₂)₂CH₃), 2.26 (2H, t, ³J = 8.0 Hz, CH₂CH₂(CH₂)₂CH₃),

2

1

(CH₂), 32.3 (CH₂), 52.1 (d, J_C,P= 5.6 Hz, OCH₃), 110.3 (d, J_C,P

=

234.2 Hz, C-sp²), 126.2 (ArC), 128.3 (ArC), 128.5 (ArC), 128.6

(ArC), 129.8 (d, ³J_C,P= 14.1 Hz, C-sp²), 130.1 (ArC), 131.5 (d, ⁴J_C,P

=

3

2.32 (2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.63 (2H, t, J = 7.2 Hz,

8.4 Hz, C-sp²), 134.2 (ArC), 137.3 (ArC), 138.3 (ArC), 144.7 (d, ²J_C,P

= 17.5 Hz, C-sp²) ppm. HRMS (ESI): MH⁺, found 416.1185.

C₂₂H₂₄ClNO₃P requires 416.1182.

CH₂CH₂CH₂), 2.82−2.86 (2H, m, CH₂CH₂CH₂), 3.50 (6H, d, ³J_H,P

=

3

11.2 Hz, 2 × OCH₃), 3.83 (3H, s, OCH₃), 6.91 (2H, d, J = 8.8 Hz,

ArH), 7.18 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

3

Dimethyl 3-(4-Methylbenzyl)-2-phenyl-2,4,5,6-

CDCl₃): δ 13.8 (CH₃), 22.2 (CH₂), 25.2 (CH₂), 26.0 (CH₂), 26.5

2

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10f). Yellow-

(CH₂), 27.9 (CH₂), 30.4 (CH₂), 31.3 (CH₂), 52.0 (d, J_C,P= 5.5 Hz,

1

OCH₃), 55.3 (OCH₃), 109.4 (d, J_C,P= 235.0 Hz, C-sp²), 113.4

ish oil. Yield 0.23 g, 58%. H NMR (400 MHz, CDCl₃): δ 2.26−2.31

3

(ArC), 127.8 (d, J_C,P= 14.3 Hz, C-sp²), 129.7 (ArC), 131.8 (ArC),

(5H, m, CH₂CH₂CH₂and CH₃), 2.33−2.37 (2H, m, CH₂CH₂CH₂),

3

4

2

134.0 (d, J_C,P= 8.4 Hz, C-sp²), 144.3 (d, J_C,P= 17.6 Hz, C-sp²),

159.1 (ArC) ppm. HRMS (ESI): MNa⁺, found 414.1806.

C₂₁H₃₀NNaO₄P requires 414.1805.

2.83−2.87 (2H, m, CH₂CH₂CH₂), 3.49 (6H, d, J_H,P= 11.2 Hz, 2 ×

3

OCH₃), 3.60 (2H, br. s, CH₂), 6.82 (2H, d, J = 8.0 Hz, ArH), 7. 00

3

(2H, d, J = 7.6 Hz, ArH), 7.20−7.22 (2H, m, ArH), 7.37−7.39 (3H,

m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 20.9 (CH₃), 24.8

Dimethyl 2-(4-Fluorophenyl)-3-pentyl-2,4,5,6-

2

(CH₂), 26.5 (CH₂), 30.3 (CH₂), 31.8 (CH₂), 52.0 (d, J_C,P= 5.5 Hz,

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10k). Yellow-

1

OCH₃), 109.9 (d, ¹J_C,P= 234.7 Hz, C-sp²), 128.3 (ArC), 128.3 (ArC),

ish oil. Yield 0.3 g, 80%. H NMR (400 MHz, CDCl₃): δ 0.81 (3H, t,

³J

=

6.8 Hz, CH₂(CH₂)₃CH₃), 1.10−1.22 (4H, m,

CH₂CH₂(CH₂)₂CH₃), 1.42 (2H, quint, ³J

7.6 Hz,

CH₂CH₂(CH₂)₂CH₃), 2.26 (2H, t, ³J = 7.6 Hz, CH₂CH₂(CH₂)₂CH₃),

3

128.4 (ArC), 128.7 (ArC), 128.8 (ArC), 129.2 (d, J_C,P= 14.2 Hz, C-

sp²), 131.8 (d,, ⁴J_C₂_,P= 8.5 Hz, C-sp²), 135.4 (ArC), 135.4 (ArC), 138.7

(ArC), 144.5 (d, J_C,P= 17.5 Hz, C-sp²) ppm. HRMS (ESI): MNa⁺,

found 418.1541. C₂₃H₂₆NNaO₃P requires 418.1543.

=

3

2.33 (2H, quint, J = 6.8 Hz, CH₂CH₂CH₂), 2.63 (2H, t, J = 6.8 Hz,

N

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

3

4

CH₂CH₂CH₂), 2.83 (2H, td, J_HH= 7.0 Hz, J_HP= 1.6 Hz,

128.7 (ArC), 133.2 (d, J_C,P= 8.4 Hz, C-sp²), 138.9 (ArC), 144.7 (d,

3

CH₂CH₂CH₂), 3.52 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 7.07−7.12

²J_C,P= 17.5 Hz, C-sp²). HRMS (ESI): MNa⁺, found 368.1387.

C₁₉H₂₄NNaO₃P requires 368.1386.

Dimethyl 3-(Cyclopropylmethyl)-2-(4-methoxyphenyl)-

2,4,5,6-tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10p).

(2H, m, ArH), 7.23−7.26 (2H, m, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 13.8 (CH₃), 22.2 (CH₂), 25.1 (CH₂), 26.0 (CH₂), 26.5

2

(CH₂), 27.9 (CH₂), 30.4 (CH₂), 31.4 (CH₂), 52.1 (d, J_C,P= 5.5 Hz,

1

2

1

OCH₃), 109.4 (d, J_C,P= 235.8 Hz, C-sp²), 115.3 (d, J_C,F= 22.6 Hz,

Yellowish oil. Yield 0.26 g, 76%. H NMR (300 MHz, CDCl₃): δ

ArC), 128.3 (d, ³J_C,P= 14.3 Hz, C-sp²), 130.4 (d, ³J_C,F= 8.7 Hz, ArC),

−0.03−0.00 (2H, m, CH(CH₂)₂), 0.39−0.43 (2H, m, CH(CH₂)₂),

0.76−0.86 (1H, m, CH(CH₂)₂), 2.17 (2H, d, ³J = 7.2 Hz, CH₂), 2.33

133.9 (d, J_C,P= 8.2 Hz, C-sp²), 134.9 (d, J_C,F= 3.1 Hz, ArC), 144.8

4

3

(d, J_C,P= 17.5 Hz, C-sp²), 162.1 (d, J_C,F= 246.5 Hz, ArC) ppm.

HRMS (ESI): MH⁺, found 380.1791. C₂₀H₂₈FNO₃P requires

380.1785.

2

1

(2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.71 (2H, t, J = 7.2 Hz,

3

CH₂CH₂CH₂), 2.85 (2H, t, J = 7.2 Hz, CH₂CH₂CH₂), 3.50 (6H, d,

³J_H,P= 11.2 Hz, 2 × OCH₃), 3.82 (3H, s, OCH₃), 6.90 (2H, d, ³J = 8.4

Hz, ArH), 7.18 (2H, d, ³J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 5.0 (CH₂), 9.7 (CH), 25.5 (CH₂), 26.5 (CH₂), 30.3 (CH₂),

Dimethyl 2-(4-Chlorophenyl)-3-pentyl-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10l). Yellow-

ish oil. Yield 0.3 g, 76%. ¹H NMR (400 MHz, CDCl₃): δ 0.81 (3H, t,

6.8 Hz, CH₂(CH₂)₃CH₃), 1.12−1.21 (4H, m,

CH₂CH₂(CH₂)₂CH₃), 1.42 (2H, quint, ³J

7.6 Hz,

CH₂CH₂(CH₂)₂CH₃), 2.26 (2H, t, ³J = 7.6 Hz, CH₂CH₂(CH₂)₂CH₃),

2

31.3 (CH₂), 52.0 (d, J_C,P= 5.5 Hz, OCH₃), 55.2 (OCH₃), 109.6 (d,

³J

=

¹J_C,P= 234.3 Hz, C-sp²), 113.4 (ArC), 128.0 (d, J_C,P= 14.2 Hz, C-

3

sp²), 129.7 (ArC), 131.7 (ArC), 133.5 (d, ⁴J_C,P= 8.3 Hz, C-sp²), 144.4

=

(d, J_C,P= 17.7 Hz, C-sp²), 159.1 (ArC). HRMS (ESI): MNa⁺, found

2

3

2.33 (2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.64 (2H, t, J = 7.2 Hz,

398.1494. C₂₀H₂₆NNaO₄P requires 398.1492.

Dimethyl 3-(Cyclopropylmethyl)-2-(4-ethoxyphenyl)-

2,4,5,6-tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10r).

3

4

CH₂CH₂CH₂), 2.83 (2H, td, J_HH= 7.0 Hz, J_HP= 1.6 Hz,

3

CH₂CH₂CH₂), 3.52 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 7.21 (2H,

d, J = 8.8 Hz, ArH), 7.39 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ 13.8 (CH₃), 22.2 (CH₂), 25.1 (CH₂), 26.0

(CH₂), 26.5 (CH₂), 27.9 (CH₂), 30.4 (CH₂), 31.4 (CH₂), 52.1 (d,

3

1

Yellowish oil. Yield 0.23 g, 59%. H NMR (300 MHz, CDCl₃): δ

−0.03−0.00 (2H, m, CH(CH₂)₂), 0.38−0.43 (2H, m, CH(CH₂)₂),

0.76−0.86 (1H, m, CH(CH₂)₂), 1.42 (3H, t, ³J = 7.2 Hz, OCH₂CH₃),

2.17 (2H, d, ³J = 7.2 Hz, CH₂), 2.38 (2H, quint, ³J = 7.2 Hz,

CH₂CH₂CH₂), 2.71 (2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.85 (2H, t, ³J

²J_C,P= 5.6 Hz, OCH₃), 109.4 (d, J_C,P= 235.0 Hz, C-sp²), 128.5 (d,

1

³J_C,P= 14.2 Hz, C-sp²), 128.6 (ArC), 130.0 (ArC), 133.7 (d, ⁴J_C,P= 8.2

Hz, C-sp²),134.1 (ArC), 137.5 (ArC), 144.9 (d, ²J_C,P= 17.4 Hz, C-sp²)

ppm. HRMS (ESI): MH⁺, found 396.1500. C₂₀H₂₈ClNO₃P requires

396.1490.

3

= 7.2 Hz, CH₂CH₂CH₂), 3.50 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃),

4.04 (3H, q, ³J = 7.2 Hz, OCH₂CH₃), 6.88 (2H, d, ³J = 8.8 Hz, ArH),

7.16 (2H, d, ³J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

5.0 (CH₂), 9.7 (CH), 14.7 (CH₃), 25.5 (CH₂), 26.5 (CH₂), 30.3

Dimethyl 3-Hexyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta[c]-

2

1

(CH₂), 31.4 (CH₂), 52.0 (d, J_C,P= 5.5 Hz, OCH₃), 63.5 (OCH₃),

pyrrol-1-ylphosphonate (10m). Yellowish oil. Yield 0.3 g, 80%. H

109.6 (d, ¹J_C,P= 234.6 Hz, C-sp²), 113.9, 128.0 (d, ³J_C,P= 14.3 Hz, C-

sp²), 129.7 (ArC), 131.6 (ArC), 133.5 (d, ⁴J_C,P= 8.5 Hz, C-sp²), 144.4

NMR (400 MHz, CDCl₃): δ 0.82 (3H, t, ³J = 6.8 Hz,

CH₂(CH₂)₄CH₃), 1.14−1.21 (6H, m, CH₂CH₂(CH₂)₃CH₃), 1.34−

1.46 (2H, m, CH₂CH₂(CH₂)₃CH₃), 2.28 (2H, t, ³J = 8.0 Hz,

(d, J_C,P= 17.5 Hz, C-sp²), 158.6 (ArC). HRMS (ESI): MNa⁺, found

2

3

412.1646. C₂₁H₂₈NNaO₄P requires 412.1648.

CH₂(CH₂)₄CH₃), 2.34 (2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.65

(2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.83−2.87 (2H, m, CH₂CH₂CH₂),

Dimethyl 3-Methyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

[c]pyrrol-1-ylphosphonate (10s). Yellowish oil. Yield 0.2 g, 66%.

¹H NMR (400 MHz, CDCl₃): δ 1.93 (3H, s, CH₃), 2.34 (2H, quint, ³J

3

3.48 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 7.26−7.28 (2H, m, ArH),

7.39−7.43 (3H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 14.0

(CH₃), 22.4 (CH₂), 25.2 (CH₂), 26.1 (CH₂), 26.5 (CH₂), 28.2 (CH₂),

28.9 (CH₂), 30.5 (CH₂), 31.3 (CH₂), 52.1 (d, ²J_C,P= 5.6 Hz, OCH₃),

= 6.8 Hz, CH₂CH₂CH₂), 2.60 (2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.86

3

4

(2H, td, J_H,H= 7.2 Hz, J_H,P= 1.2 Hz, CH₂CH₂CH₂), 3.49 (6H, d,

³J_H,P= 11.6 Hz, 2 × OCH₃), 7.26−7.28 (2H, m, ArH), 7.37−7.45 (3H,

m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 11.6 (CH₃), 24.4

(CH₂), 26.8 (CH₂), 30.4 (CH₂), 52.1 (d, ²J_C,P= 5.5 Hz, OCH₃), 109.4

109.2 (d, J_C,P= 235.2 Hz, C-sp²), 128.1 (d, J_C,P= 14.3 Hz, C-sp²),

1

3

4

128.2 (ArC), 128.4 (ArC), 128.7 (ArC), 133.8 (d, J_C,P= 8.4 Hz, C-

sp²), 139.0 (ArC), 144.8 (d, J_C,P= 17.5 Hz, C-sp²) ppm. HRMS

2

(ESI): MNa⁺, found 398.1862. C₂₁H₃₀NNaO₃P requires 398.1856.

Dimethyl 3-Hexyl-2-(4-methoxyphenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10n). Yellow-

ish oil. Yield 0.26 g, 63%. ¹H NMR (400 MHz, CDCl₃): δ 0.82 (3H, t,

(d, J_C,P= 235.1 Hz, C-sp²), 128.2 (ArC), 128.4 (ArC), 128.5 (ArC),

1

128.8 (d, J_C,P= 14.3 Hz, C-sp²), 129.0 (d, J_C,P= 8.8 Hz, C-sp²),

3

4

139.0 (ArC), 144.6 (d, J_C,P= 17.5 Hz, C-sp²) ppm. HRMS (ESI):

2

MH⁺, found 306.1263. C₁₆H₂₁NO₃P requires 306.1254.

³J

= 6.8 Hz, CH₂(CH₂)₄CH₃), 1.14−1.24 (6H, m,

Dimethyl 3-Benzyl-2-phenyl-2H-isoindol-1-ylphosphonate

(11a). Light orange solid, mp 82−83 °C. Yield 0.28 g, 72%. ¹H

NMR (400 MHz, CDCl₃): δ 3.53 (6H, d, ³J_H,P= 11.6 Hz, 2 × OCH₃),

4.14 (2H, s, CH₂), 6.82−6.85 (2H, m, ArH), 7.09−7.15 (5H, m, ArH),

7.22- 7.24 (1H, m, ArH), 7.37−7.49 (4H, m, ArH), 7.57−7.64 (4H, m,

ArH), 7.56−7.61 (1H, m, ArH), 8.11 (1H, dt, J = 8.8; 0.8 Hz, ArH)

CH₂CH₂(CH₂)₃CH₃), 1.37−1.45 (2H, m, CH₂CH₂(CH₂)₃CH₃),

3

2.26 (2H, t, J = 7.6 Hz, CH₂(CH₂)₄CH₃), 2.32 (2H, quint, J = 6.8

Hz, CH₂CH₂CH₂), 2.63 (2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.81−2.85

(2H, m, CH₂CH₂CH₂), 3.50 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.83

3

(3H, s, OCH₃), 6.91 (2H, d, J = 8.8 Hz, ArH), 7.18 (2H, d, J = 8.8

Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.9 (CH₃), 22.4

(CH₂), 25.1 (CH₂), 26.0 (CH₂), 26.5 (CH₂), 28.2 (CH₂), 28.9 (CH₂),

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 31.1 (d, J_C,P= 1.1 Hz, CH₂),

4

52.2 (d, ²J_C,P= 5.4 Hz, 2 × OCH₃), 106.5 (d, ¹J_C,P= 235.4 Hz, ArC),

3

2

119.7 (ArC), 120.3 (ArC), 121.7 (ArC), 123.3 (d, J_C,P= 13.6 Hz,

30.4 (CH₂), 31.3 (CH₂), 52.0 (d, J_C,P= 5.4 Hz, OCH₃), 55.3

ArC), 125.0 (d, ⁴J_C,P= 0.4 Hz, ArC), 126.3 (ArC), 128.1 (ArC), 128.2

(ArC), 128.3 (2 × ArC), 129.2 (ArC), 131.9 (d, ²J_C,P= 8.6 Hz, ArC),

132.1 (d, ²J_C,P= 18.2 Hz, ArC), 138.0 (ArC), 138.4 (d, ⁵J_C,P= 0.7 Hz,

ArC) ppm. HRMS (ESI): MH⁺, found 392.1410. C₂₃H₂₃NO₃P

requires 392.1410.

(OCH₃), 109.3 (d, J_C,P= 235.0 Hz, C-sp²), 113.4 (ArC), 127.8 (d,

1

³J_C,P= 14.4 Hz, C-sp²), 129.7 (ArC), 131.7 (ArC), 134.0 (d, ⁴J_C,P= 8.4

Hz, C-sp²), 144.4 (d, J_C,P= 17.5 Hz, C-sp²) ppm. HRMS (ESI):

2

MNa⁺, found 428.1963. C₂₂H₃₂NNaO₄P requires 428.1961.

Dimethyl 3-(Cyclopropylmethyl)-2-phenyl-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (10o). Yellow-

ish oil. Yield 0.26 g, 76%. ¹H NMR (300 MHz, CDCl₃): δ −0.04−0.00

(2H, m, CH(CH₂)₂), 0.38−0.43 (2H, m, CH(CH₂)₂), 0.76−0.89 (1H,

Dimethyl 2,3-Diphenyl-1,2-dihydroisoquinolin-1-ylphosph-

onate (12a). Light orange solid, mp 128−129 °C. Yield 0.34 g, 86%.

¹H NMR (400 MHz, CDCl₃): δ 3.69 (3H, d, ³J_H,P= 10.4 Hz, OCH₃),

3

1

3

3.76 (3H, d, J_H,P= 10.4 Hz, OCH₃), 5.57 (1H, d, J_H,P= 18.8 Hz,

m, CH(CH₂)₂), 2.18 (2H, d, J = 6.8 Hz, CH₂), 2.31−2.38 (2H, m,

CH₂CH₂CH₂), 2.73 (2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.87 (2H, t, ³J

2

CH), 6.62 (1H, s, C_spH), 6.91−6.95 (1H, m, ArH), 7.16−7.17 (3H,

3

m, ArH), 7.21−7.28 (4H, m, ArH), 7.30−7.34 (4H, m, ArH), 7.65−

= 7.2 Hz, CH₂CH₂CH₂), 3.48 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃),

7.67 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 53.1 (d,

7.26−7.28 (2H, m, ArH), 7.38−7.42 (2H, m, ArH) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ 5.0 (CH₂), 9.6 (CH), 25.5 (CH₂), 26.5 (CH₂),

²J_C,P= 6.4 Hz, OCH₃), 53.2 (d, ²J_C,P= 6.2 Hz, OCH₃), 63.8 (d, ¹J_C,P

=

2

30.4 (CH₂), 31.4 (CH₂), 52.0 (d, J_C,P= 5.5 Hz, OCH₃), 109.5 (d,

162.2 Hz, CH), 111.9 (C_spH), 122.4 (ArC), 122.6 (d, J_C,P= 2.0 Hz,

ArC), 124.3 (d, J_C,P= 2.6 Hz, ArC), 125.2 (d, J_C,P= 3.1 Hz, ArC),

¹J_C,P= 234.3 Hz, C-sp²), 128.2 (ArC), 128.4 (ArC), 128.5 (C-sp²),

2

O

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

4

126.6 (d, J_C,P= 1.9 Hz, ArC), 127.1 (d, J_C,P= 5.9 Hz, ArC), 127.5

(CH₂), 23.4 (CH₂), 23.5 (CH₂), 30.2 (d,, J_C,P= 1.1 Hz, CH₂), 51.8

(d, ²J_C,P= 5.5 Hz, 2 × OCH₃), 112.7 (d, ¹J_C,P= 230.7 Hz, ArC), 118.7

2

(ArC), 128.0 (ArC), 128.3 (ArC), 128.3 (d, J_C,P= 3.1 Hz, ArC),

3

128.5 (ArC), 132.8 (d, J_C,P= 3.2 Hz, ArC), 137.0 (ArC), 142.0 (d,

(d, J_C,P= 14.9 Hz, ArC), 127.9 (ArC), 128.1 (ArC), 128.2 (ArC),

J_C,P= 1.6 Hz, ArC), 147.4 (d, ³J_C,P= 7.0 Hz, ArC) ppm. HRMS (ESI):

MNa⁺, found 414.1222. C₂₃H₂₂NNaO₃P requires 414.1230.

Dimethyl 3-Benzyl-2-phenyl-4,5,6,7-tetrahydro-2H-isoindol-

128.8 (2 × ArC), 134.0 (d, ²J_C,P= 19.2 Hz, ArC), 135.2 (d, ³J_C,P= 9.9

Hz, ArC), 135.3 (ArC), 135.7 (ArC), 138.7 (ArC) ppm. HRMS (ESI):

MNa⁺, found 432.1706. C₂₄H₂₈NNaO₃P requires 432.1699.

1

1-ylphosphonate (14a). Yellowish oil. Yield 0.32 g, 82%. H NMR

Dimethyl 2-(4-Methoxyphenyl)-3-(4-methylbenzyl)-4,5,6,7-

tetrahydro-2H-isoindol-1-ylphosphonate (14e). Yellowish oil.

Yield 0.35 g, 79%. H NMR (400 MHz, CDCl₃): δ 1.75−1.77 (4H,

(400 MHz, CDCl₃): δ 1.77−1.79 (4H, m, 2 × CH₂), 2.46 (2H, t, J =

5.6 Hz, CH₂), 2.88 (2H, t, J = 5.6 Hz, CH₂), 3.46 (6H, d, ³J_H,P= 11.2

Hz, 2 × OCH₃), 3.67 (2H, s, CH₂), 6.79−6.81 (2H, m, ArH), 7.07

1

m, 2 × CH₂), 2.27 (3H, s, CH₃), 2.42−2.45 (2H, m, CH₂), 2.85−2.87

(2H, m, CH₂), 3.49 (6H, d, ³J_H,P= 11.6 Hz, 2 × OCH₃), 3.62 (2H, s,

CH₂), 3.81 (3H, s, OCH₃), 6.72 (2H, d, J = 7.6 Hz, ArH), 6.80 (2H, d,

J = 8.8 Hz, ArH), 6.96−7.00 (4H, m, ArH) ppm. ¹³C NMR (100

(2H, dd, J = 8.2; 1.6 Hz, ArH), 7.10−7.16 (3H, m, ArH), 7.27−7.34

3

(3H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.8 (d, J_C,P

=

4

1.1 Hz, CH₂), 23.1 (CH₂), 23.3 (CH₂), 23.5 (CH₂), 30.6 (d, J_C,P

3

2

1

MHz, CDCl₃): δ 20.9 (CH₃), 21.8 (d, J_C,P= 1.1 Hz, CH₂), 23.2

1.0 Hz, CH₂), 51.7 (d, J_C,P₃= 5.5 Hz, 2 × OCH₃), 112.9 (d, J_C,P

4

(CH₂), 23.4 (CH₂), 23.6 (CH₂), 30.2 (d,, J_C,P= 1.0 Hz, CH₂), 51.9

230.2 Hz, ArC), 118.7 (d, J_C,P= 14.7 Hz, ArC), 125.8 (ArC), 128.0

2

1

2

(d, J_C,P= 5.4 Hz, 2 × OCH₃), 55.3 (OCH₃), 112.6 (d, J_C,P= 230.5

(ArC), 128.1 (2 × ArC), 128.2 (ArC), 128.8 (ArC), 133.9 (d, J_C,P

=

Hz, ArC), 113.2 (ArC), 118.5 (d, ³J_C,P= 14.8 Hz, ArC), 127.9 (ArC),

3

19.1 Hz, ArC), 134.8 (d, J_C,P= 9.8 Hz, ArC), 138.6 (ArC), 138.7

(ArC) ppm. HRMS (ESI): MNa⁺, found 418.1548. C₂₃H₂₆NNaO₃P

requires 418.1543.

2

128.8 (ArC), 129.8 (ArC), 131.3 (ArC), 133.9 (d, J_C,P= 19.2 Hz,

3

ArC), 135.3 (ArC), 135.5 (d, J_C,P= 10.0 Hz, ArC), 135.8 (ArC),

159.2 (ArC) ppm. HRMS (ESI): MNa⁺, found 462.1795.

C₂₅H₃₀NNaO₄P requires 462.1805.

Dimethyl 3-Benzyl-2-(4-methoxyphenyl)-4,5,6,7-tetrahydro-

2H-isoindol-1-ylphosphonate (14b). Brownish solid, mp 108−109

°C. Yield 0.4 g, 95%. ¹H NMR (400 MHz, CDCl₃): δ 1.76−1.78 (4H,

m, 2 × CH₂), 2.45 (2H, t, J = 5.6 Hz, CH₂), 2.86 (2H, t, J = 5.6 Hz,

Dimethyl 3-Butyl-2-phenyl-4,5,6,7-tetrahydro-2H-isoindol-

1-ylphosphonate (14g). Yellowish oil. Yield 0.32 g, 89%. ¹H

NMR (400 MHz, CDCl₃): δ 0.72 (3H, t, J = 7.2 Hz, CH₃), 1.11 (2H,

sexst., J = 7.2 Hz, CH₂), 1.22−1.26 (2H, m, CH₂), 1.74−1.77 (4H, m,

2 × CH_2chex), 2.27 (2H, t, J = 7.6 Hz, CH₂), 2.48 (2H, br. s, CH_2chex),

3

CH₂), 3.48 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 3.66 (2H, s, CH₂),

3.80 (3H, s, OCH₃), 6.79 (2H, d, J = 8.8 Hz, ArH), 6.81−6.83 (2H, m,

ArH), 6.97 (3H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 21.8 (d, ³J_C,P= 1.0 Hz, CH₂), 23.2 (CH₂), 23.4 (CH₂), 23.6

3

2.83 (2H, br. s, CH_2chex), 3.45 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃),

7.22−7.25 (2H, m, ArH), 7.39−7.41 (3H, m, ArH) ppm. ¹³C NMR

4

2

(CH₂), 30.7 (d, J_C,P= 1.0 Hz, CH₂), 51.8 (d, J_C,P= 5.4 Hz, 2 ×

OCH₃), 55.3 (OCH₃), 113.0 (d, ¹J_C,P= 230.3 Hz, ArC), 113.2 (ArC),

118.6 (d, ³J_C,P= 14.8 Hz, ArC), 125.8 (ArC), 128.1 (2 × ArC), 129.8

(100 MHz, CDCl₃): δ 13.5 (CH₃), 21.7 (d, ³J_C,P= 1.2 Hz, CH₂), 22.3

4

(CH₂), 23.1 (CH₂), 23.4 (CH₂), 23.5 (CH₂), 24.3 (d, J_C,P= 1.1 Hz,

CH₂), 31.0 (CH₂), 51.8 (d, ²J_C,P= 5.4 Hz, 2 × OCH₃), 112.0 (d, ¹J_C,P

(ArC), 131.3 (ArC), 133.7 (d, ²J_C,P= 19.2 Hz, ArC), 135.2 (d, ³J_C,P

=

3

9.9 Hz, ArC), 138.9 (ArC), 159.2 (ArC) ppm. HRMS (ESI): MNa⁺,

found 448.1645. C₂₄H₂₈NNaO₄P requires 448.1648.

= 230.8 Hz, ArC), 117.6 (d, J_C,P= 14.8 Hz, ArC), 128.2 (2 × ArC),

128.8 (ArC), 134.0 (d, ²J_C,P= 19.2 Hz, ArC), 137.4 (d, ³J_C,P= 9.7 Hz,

ArC), 138.9 (ArC) ppm. HRMS (ESI): MNa⁺, found 384.1695.

C₂₀H₂₈NNaO₃P requires 384.1699.

Dimethyl 3-Benzyl-2-(4-ﬂuorophenyl)-4,5,6,7-tetrahydro-

2H-isoindol-1-ylphosphonate (14c). Yellowish solid, mp 95−96

1

°C. Yield 0.23 g, 56%. H NMR (400 MHz, CDCl₃): δ 1.77−1.79

Dimethyl 3-Butyl-2-(4-methoxyphenyl)-4,5,6,7-tetrahydro-

2H-isoindol-1-ylphosphonate (14h). Yellowish oil. Yield 0.39 g,

99%. H NMR (400 MHz, CDCl₃): δ 0.74 (3H, t, J = 7.2 Hz, CH₃),

(4H, m, 2 × CH₂), 2.48−2.49 (2H, m, CH₂), 2.85−2.86 (2H, m,

1

3

CH₂), 3.49 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 3.66 (2H, s, CH₂),

1.13 (2H, sexst., J = 7.2 Hz, CH₂), 1.20−1.29 (2H, m, CH₂), 1.74−

1.76 (4H, m, 2 × CH_2chex), 2.26 (2H, t, J = 7.6 Hz, CH₂), 2.47 (2H, br.

s, CH_2chex), 2.82 (2H, br. s, CH_2chex), 3.48 (6H, d, ³J_H,P= 11.2 Hz, 2 ×

OCH₃), 3.83 (3H, s, OCH₃), 6.90 (2H, d, J = 8.8 Hz, ArH), 7.14 (2H,

d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.6

(CH₃), 21.7 (CH₂), 22.3 (CH₂), 23.1 (CH₂), 23.4 (CH₂), 23.5 (CH₂),

6.78−6.80 (2H, m, ArH), 6.93−7.01 (4H, m, ArH), 7.11−7.17 (3H,

m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.8 (d, ³J_C,P= 1.0 Hz,

4

CH₂), 23.1 (CH₂), 23.3 (CH₂), 23.5 (CH₂), 30.6 (d, J_C,P= 1.1 Hz,

CH₂), 51.8 (d, ²J_C,P= 5.5 Hz, 2 × OCH₃), 113.2 (d, ¹J_C,P= 230.2 Hz,

ArC), 115.0 (d, ²J_C,F= 22.5 Hz, ArC), 119.0 (d, ³J_C,P= 14.7 Hz, ArC),

3

126.0 (ArC), 128.0 (ArC), 128.2 (ArC), 130.5 (d, J_C,F= 8.7 Hz,

2

4

24.3 (CH₂), 31.1 (CH₂), 51.8 (d, J_C,P= 5.3 Hz, 2 × OCH₃), 55.3

ArC), 133.9 (d, J_C,P= 19.0 Hz, ArC), 134.6 (d, J_C,P= 3.0 Hz, ArC),

135.0 (d, ³J_C,P= 9.8 Hz, ArC), 138.6 (ArC), 162.1 (d, ¹J_C,F= 246.5 Hz,

ArC) ppm. HRMS (ESI): MNa⁺, found 436.1452. C₂₃H₂₅FNNaO₃P

requires 436.1448.

(OCH₃), 111.8 (d, ¹J_C,P= 231.3 Hz, ArC), 113.3 (ArC), 117.4 (d, ³J_C,P

= 14.9 Hz, ArC), 129.7 (ArC), 131.6 (ArC), 133.8 (d, ²J_C,P= 19.4 Hz,

ArC), 137.7 (d, ³J_C,P= 9.7 Hz, ArC), 159.1 (ArC) ppm. HRMS (ESI):

MNa⁺, found 414.1801. C₂₁H₃₀NNaO₄P requires 414.1805.

Dimethyl 3-Benzyl-2-(4-chlorophenyl)-4,5,6,7-tetrahydro-

Dimethyl 3-Butyl-2-(4-ﬂuorophenyl)-4,5,6,7-tetrahydro-2H-

isoindol-1-ylphosphonate (14i). Yellowish oil. Yield 0.31 g, 81%.

¹H NMR (400 MHz, CDCl₃): δ 0.73 (3H, t, J = 7.2 Hz, CH₃), 1.12

2H-isoindol-1-ylphosphonate (14d). Yellowish oil. Yield 0.29 g,

1

68%. H NMR (400 MHz, CDCl₃): δ 1.77−1.78 (4H, m, 2 × CH₂),

2.46−2.48 (2H, m, CH₂), 2.84−2.86 (2H, m, CH₂), 3.49 (6H, d, ³J_H,P

= 11.6 Hz, 2 × OCH₃), 3.66 (2H, s, CH₂), 6.78−6.80 (2H, m, ArH),

6.97 (2H, d, J = 8.4 Hz, ArH), 7.10−7.18 (3H, m, ArH), 7.25 (2H, d, J

(2H, sexst., J = 7.2 Hz, CH₂), 1.21−1.25 (2H, m, CH₂), 1.72−1.76

(4H, m, 2 × CH_2chex), 2.25 (2H, t, J = 8.0 Hz, CH₂), 2.46 (2H, br. s,

3

= 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.7 (d, ³J_C,P

=

CH_2chex), 2.80 (2H, br. s, CH_2chex), 3.48 (6H, d, J_H,P= 11.2 Hz, 2 ×

OCH₃), 7.06−7.10 (2H, m, ArH), 7.19−7.22 (2H, m, ArH) ppm. ¹³

C

4

1.1 Hz, CH₂), 23.1 (CH₂), 23.3 (CH₂), 23.4 (CH₂), 30.6 (d, J_C,P

3

2

1

NMR (100 MHz, CDCl₃): δ 13.6 (CH₃), 21.7 (d, J_C,P= 1.2 Hz,

CH₂), 22.4 (CH₂), 23.1 (CH₂), 23.4 (CH₂), 23.5 (CH₂), 24.4 (CH₂),

31.1 (CH₂), 51.9 (d, ²J_C,P= 5.4 Hz, 2 × OCH₃), 112.2 (d, ¹J_C,P= 230.8

1.0 Hz, CH₂), 51.9 (d, J_C,P₃= 5.5 Hz, 2 × OCH₃), 113.1 (d, J_C,P

229.9 Hz, ArC), 119.1 (d, J_C,P= 14.6 Hz, ArC), 126.0 (ArC), 127.9

(ArC), 128.2 (ArC), 128.3 (ArC), 130.1 (ArC), 134.1 (d, J_C,P= 18.9

2

3

Hz, ArC), 115.2 (d, J_C,F= 22.6 Hz, ArC), 117.8 (d, J_C,P= 14.8 Hz,

Hz, ArC), 134.1 (ArC), 134.9 (d, J_C,P= 9.7 Hz, ArC), 137.2 (ArC),

3

2

138.5 (ArC) ppm. HRMS (ESI): MNa⁺, found 452.1157.

C₂₃H₂₅ClNNaO₃P requires 452.1153.

ArC), 130.5 (d, J_C,F= 8.6 Hz, ArC), 134.1 (d, J_C,P= 19.2 Hz, ArC),

134.0 (d, ⁴J_C,P= 3.2 Hz, ArC), 137.6 (d, ³J_C,P= 9.5 Hz, ArC), 162.2 (d,

¹J_C,F= 246.4 Hz, ArC) ppm. HRMS (ESI): MNa⁺, found 402.1610.

C₂₀H₂₇FNNaO₃P requires 402.1605.

Dimethyl 3-(4-Methylbenzyl)-2-phenyl-4,5,6,7-tetrahydro-

2H-isoindol-1-ylphosphonate (14e). Yellowish oil. Yield 0.38 g,

1

92%. H NMR (400 MHz, CDCl₃): δ 1.76−1.78 (4H, m, 2 × CH₂),

Dimethyl 3-Pentyl-2-phenyl-4,5,6,7-tetrahydro-2H-isoindol-

1

2.27 (3H, s, CH₃), 2.43−2.47 (2H, m, CH₂), 2.87−2.89 (2H, m,

1-ylphosphonate (14j). Brownish oil. Yield 0.33 g, 88%. H NMR

3

CH₂), 3.47 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 3.63 (2H, s, CH₂),

(400 MHz, CDCl₃): δ 0.75 (3H, t, J = 7.2 Hz, CH₃), 1.05−1.15 (4H,

m, 2 × CH₂), 1.22−1.29 (2H, m, CH₂), 1.74−1.77 (4H, m, 2 ×

CH_2chex), 2.26 (2H, t, J = 7.6 Hz, CH₂), 2.48 (2H, br. s, CH_2chex), 2.83

6.70 (2H, d, J = 8.0 Hz, ArH), 6.96 (2H, d, J = 8.0 Hz, ArH), 7.08−

7.10 (2H, m, ArH), 7.28−7.35 (3H, m, ArH) ppm. ¹³C NMR (100

3

MHz, CDCl₃): δ 20.9 (CH₃), 21.8 (d, J_C,P= 1.0 Hz, CH₂), 23.2

(2H, br. s, CH_2chex), 3.45 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃), 7.22−

P

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

7.24 (2H, m, ArH), 7.39−7.41 (3H, m, ArH) ppm. ¹³C NMR (100

was added molecular iodine (0.254 g, 1 mmol) at 0 °C, together with

phenyliodine diacetate (0.644 g, 2 mmol). The resulting stirring

solution was allowed to warm to room temperature. When the

completion of the reaction was observed by TLC (after 0.5−1 h), the

solution was quenched with aqueous sodium thiosulfate. The organic

layer was separated, washed with aqueous sodium thiosulfate (2 × 20

mL) and then with water (2 × 20 mL), and dried over anhydrous

Na₂SO₄. After the evaporation of solvent under reduced pressure, the

residue was puriﬁed by ﬂash column chromatography eluting with

hexane−ethyl acetate mixtures.

3

MHz, CDCl₃): δ 13.7 (CH₃), 21.7 (d, J_C,P= 1.2 Hz, CH₂), 22.0

(CH₂), 23.1 (CH₂), 23.4 (CH₂), 23.5 (CH₂), 24.6 (d, J_C,P= 0.9 Hz,

2

CH₂), 28.4 (CH₂), 31.3 (CH₂), 51.7 (d, J_C,P= 5.5 Hz, 2 × OCH₃),

112.0 (d, ¹J_C,P= 231.0 Hz, ArC), 117.6 (d, ³J_C,P= 14.9 Hz, ArC), 128.2

2

(2 × ArC), 128.8 (ArC), 134.0 (d, J_C,P= 19.3 Hz, ArC), 137.4 (d,

³J_C,P= 9.7 Hz, ArC), 138.9 (ArC) ppm. HRMS (ESI): MNa⁺, found

398.1845. C₂₁H₃₀NNaO₃P requires 398.1856.

Dimethyl 2-(4-Methoxyphenyl)-3-pentyl-4,5,6,7-tetrahydro-

2H-isoindol-1-ylphosphonate (14k). Light brown oil. Yield 0.33 g,

1

82%. H NMR (400 MHz, CDCl₃): δ 0.77 (3H, t, J = 7.2 Hz, CH₃),

Dimethyl 3-Benzoyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

[c]pyrrol-1-ylphosphonate (13a). Yellowish oil. Yield 0.35 g, 89%.

1.08−1.15 (4H, m, 2 × CH₂), 1.22−1.30 (2H, m, CH₂), 1.75 (4H, br.

1

IR (KBr): υ_max1644 (CO) cm⁻¹. H NMR (300 MHz, CDCl₃): δ

s, 2 × CH_2chex), 2.25 (2H, t, J = 7.6 Hz, CH₂), 2.46 (2H, br. s,

2.21−2.31 (2H, m, CH₂CH₂CH₂), 2.42 (2H, t, ³J = 6.9 Hz,

3

CH_2chex), 2.82 (2H, br. s, CH_2chex), 3.47 (6H, d, J_H,P= 11.2 Hz, 2 ×

3

4

CH₂CH₂CH₂), 2.89 (2H, td, J_H,H= 7.3 Hz, J_H,P= 1.5 Hz,

OCH₃), 3.83 (3H, s, OCH₃), 6.90 (2H, d, J = 8.8 Hz, ArH), 7.14 (2H,

3

d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.7

CH₂CH₂CH₂), 3.53 (6H, d, J_H,P= 11.4 Hz, 2 × OCH₃), 7.35−7.38

3

(5H, m, ArH), 7.40−7.44 (2H, m, ArH), 7.49−7.54 (1H, m, ArH),

7.71−7.74 (2H, m, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 26.7

(CH₂), 27.7 (CH₂), 30.1 (CH₂), 52.4 (d, ²J_C,P= 5.7 Hz, OCH₃), 119.7

(CH₃), 21.7 (d, J_C,P= 0.9 Hz, CH₂), 22.1 (CH₂), 23.1 (CH₂), 23.4

4

(CH₂), 23.5 (CH₂), 24.6 (d, J_C,P= 0.7 Hz, CH₂), 28.5 (CH₂), 31.4

2

(CH₂), 51.8 (d, J_C,P= 5.4 Hz, 2 × OCH₃), 55.3 (OCH₃), 112.0 (d,

(d, J_C,P= 225.4 Hz, C-sp²), 127.9 (ArC), 128.2 (ArC), 128.2 (2 ×

1

3

¹J_C,P= 231.1 Hz, ArC), 113.3 (ArC), 117.4 (d, J_C,P= 14.8 Hz, ArC),

ArC), 129.0 (ArC), 130.2 (d, J_C,P= 9.0 Hz, C-sp²), 132.2 (ArC),

4

2

129.7 (ArC), 131.6 (ArC), 133.8 (d, J_C,P= 19.3 Hz, ArC), 137.6 (d,

138.7 (ArC), 139.2 (d, ³J_C,P= 13.8 Hz, C-sp²), 139.6 (ArC), 143.4 (d,

²J_C,P= 17.1 Hz, C-sp²), 186.3 (CO) ppm. HRMS (ESI): MNa⁺,

³J_C,P= 9.7 Hz, ArC), 159.1 (ArC) ppm. HRMS (ESI): MNa⁺, found

428.1969. C₂₂H₃₂NNaO₄P requires 428.1961.

found 418.1176. C₂₂H₂₂NNaO₄P requires 418.1179.

Dimethyl 3-(Cyclopropylmethyl)-2-phenyl-4,5,6,7-tetrahy-

Dimethyl 3-Benzoyl-2-(4-methoxyphenyl)-2,4,5,6-

dro-2H-isoindol-1-ylphosphonate (14l). Yellowish oil. Yield 0.3

1

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13b). Yellow-

g, 83%. H NMR (400 MHz, CDCl₃): δ −0.16 (2H, q, J = 4.8 Hz,

1

ish oil. Yield 0.28 g, 67%. IR (KBr): υ_max1645 (CO) cm⁻¹. H

CH(CH₂)₂), 0.26−0.30 (2H, m, CH(CH₂)₂), 0.57−0.67 (1H, m,

CH(CH₂)₂), 1.76 (4H, t, J = 3.2 Hz, 2 × CH₂), 2.21 (2H, d, J = 6.8

Hz, CH₂), 2.52 (2H, br. s, CH₂), 2.85 (2H, br. s, CH₂), 3.45 (6H, d,

³J_H,P= 11.2 Hz, 2 × OCH₃), 7.24−7.25 (2H, m, ArH), 7.37−7.41 (3H,

m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 4.8 (CH(CH₂)₂), 10.2

(CH(CH₂)₂), 21.9 (d, ³J_C,P= 1.1 Hz, CH_2chex), 23.1 (CH_2chex), 23.4 (2

× CH_2chex), 29.4 (d, ⁴J_C,P= 1.60 Hz, CH₂), 51.7 (d, ²J_C,P= 5.4 Hz, 2 ×

NMR (400 MHz, CDCl₃): δ 2.25 (2H, quint, ³J = 7.2 Hz,

3

CH₂CH₂CH₂), 2.40 (2H, t, J = 7.6 Hz, CH₂CH₂CH₂), 2.87 (2H,

3

4

3

td, J_H,H= 7.2 Hz, J_H,P= 1.2 Hz, CH₂CH₂CH₂), 3.56 (6H, d, J_H,P

=

3

11.2 Hz, 2 × OCH₃), 3.80 (3H, s, OCH₃), 6.87 (2H, d, J = 9.2 Hz,

ArH), 7.28 (2H, d, ³J = 8.8 Hz, ArH), 7.38−7.42 (2H, m, ArH), 7.49−

7.53 (1H, m, ArH), 7.71−7.73 (2H, m, ArH) ppm. ¹³C NMR (100

MHz, CDCl₃): δ 26.6 (CH₂), 27.7 (CH₂), 30.1 (CH₂), 52.4 (d, ²J_C,P

=

1

3

OCH₃), 112.3 (d, J_C,P= 230.4 Hz, ArC), 117.7 (d, J_C,P= 14.8 Hz,

1

2

5.7 Hz, OCH₃), 55.2 (OCH₃), 113.3 (ArC), 119.8 (d, J_C,P= 225.9

ArC), 128.1 (ArC), 128.2 (ArC), 128.9 (ArC), 133.9 (d, J_C,P= 19.3

Hz, C-sp²), 126.8 (ArC), 128.1 (ArC), 129.0 (ArC), 129.0 (ArC),

3

Hz, ArC), 136.9 (d, J_C,P= 9.5 Hz, ArC), 139.0 (ArC) ppm. HRMS

130.3 (d, J_C,P= 8.8 Hz, C-sp²), 132.2 (ArC), 138.8 (ArC), 138.9 (d,

4

(ESI): MNa⁺, found 382.1541. C₂₀H₂₆NNaO₃P requires 382.1543.

Dimethyl 3-(Cyclopropylmethyl)-2-(4-methoxyphenyl)-

4,5,6,7-tetrahydro-2H-isoindol-1-ylphosphonate (14m). Yellow-

³J_C,P= 14.0 Hz, C-sp²), 143.0 (d, ²J_C,P= 17.0 Hz, C-sp²), 159.1 (ArC),

186.3 (CO) ppm. HRMS (ESI): MNa⁺, found 448.1287.

1

C₂₃H₂₄NNaO₅P requires 448.1284.

ish oil. Yield 0.36 g, 92%. H NMR (400 MHz, CDCl₃): δ −0.15 to

Dimethyl 3-Benzoyl-2-(4-ethoxyphenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13c). Yellow-

−0.11 (2H, m, CH(CH₂)₂), 0.27−0.31 (2H, m, CH(CH₂)₂), 0.61−

0.65 (1H, m, CH(CH₂)₂), 1.75 (4H, br. s, 2 × CH₂), 2.19 (2H, d, J =

6.8 Hz, CH₂), 2.51 (2H, br. s, CH₂), 2.83 (2H, br. s, CH₂), 3.47 (6H,

d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 3.82 (3H, s, OCH₃), 6.89 (2H, d, J =

8.8 Hz, ArH), 7.15 (2H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100

ish oil. Yield 0.31 g, 70%. IR (KBr): υ_max1643 (CO) cm⁻¹. H

1

3

NMR (400 MHz, CDCl₃): δ 1.39 (3H, t, J = 6.8 Hz, OCH₂CH₃),

3

2.25 (2H, quint, J = 6.8 Hz, CH₂CH₂CH₂), 2.40 (2H, t, J = 7.2 Hz,

3

4

MHz, CDCl₃): δ 4.8 (CH(CH₂)₂), 10.3 (CH(CH₂)₂), 21.9 (d, ³J_C,P

=

CH₂CH₂CH₂), 2.87 (2H, td, J_H,H= 7.6 Hz, J_H,P= 1.2 Hz,

CH₂CH₂CH₂), 3.55 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 4.02 (2H, q,

³J = 7.2 Hz, OCH₂CH₃), 6.86 (2H, d, ³J = 8.8 Hz, ArH), 7.26 (2H, d,

³J = 9.2 Hz, ArH), 7.38−7.42 (2H, m, ArH), 7.49−7.53 (1H, m, ArH),

7.71−7.77 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 14.7

(OCH₂CH₃), 26.7 (CH₂), 27.7 (CH₂), 30.1 (CH₂), 52.4 (d, ²J_C,P= 5.7

1.0 Hz, CH_2chex), 23.1 (CH_2chex), 23.4 (CH_2chex), 23.5 (CH_2chex), 29.5

4

2

(d, J_C,P= 0.7 Hz, CH₂), 51.7 (d, J_C,P= 5.4 Hz, 2 × OCH₃), 55.2

(OCH₃), 112.2 (d, ¹J_C,P= 230.8 Hz, ArC), 113.2 (ArC), 117.5 (d, ³J_C,P

= 14.8 Hz, ArC), 129.9 (ArC), 131.6 (ArC), 133.8 (d, ²J_C,P= 19.4 Hz,

ArC), 137.3 (d, ³J_C,P= 9.6 Hz, ArC), 159.2 (ArC) ppm. HRMS (ESI):

MNa⁺, found 412.1650. C₂₁H₂₈NNaO₄P requires 412.1648.

1

Hz, OCH₃), 63.4 (OCH₂CH₃), 113.8 (ArC), 119.8 (d, J_C,P= 226.1

Hz, C-sp²), 128.1 (ArC), 129.0 (ArC), 129.0 (ArC), 130.3 (d, J_C,P

=

4

Dimethyl 2-(4-Chlorophenyl)-3-(cyclopropylmethyl)-4,5,6,7-

8.8 Hz, C-sp²), 132.2 (ArC), 136.3 (ArC), 138.8 (ArC), 139.0 (d, ³J_CP

tetrahydro-2H-isoindol-1-ylphosphonate (14n). Yellowish oil.

1

= 13.2 Hz, C-sp²), 143.0 (d, J_C,P= 17.0 Hz, C-sp²), 158.6 (ArC),

2

Yield 0.36 g, 92%. H NMR (400 MHz, CDCl₃): δ −0.15 to −0.11

186.3 (CO) ppm. HRMS (ESI): MNa⁺, found 462.1439.

(2H, m, CH(CH₂)₂), 0.28−0.33 (2H, m, CH(CH₂)₂), 0.55−0.65 (1H,

m, CH(CH₂)₂), 1.74−1.76 (4H, m, 2 × CH₂), 2.20 (2H, d, J = 6.8 Hz,

C₂₄H₂₆NNaO₅P requires 462.1441.

CH₂), 2.51 (2H, br. s, CH₂), 2.82 (2H, br. s, CH₂), 3.49 (6H, d, ³J_H,P

=

Dimethyl 3-Benzoyl-2-(4-ﬂuorophenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13d). Yellow-

11.6 Hz, 2 × OCH₃), 7.19 (2H, d, J = 8.8 Hz, ArH), 7.37 (2H, d, J =

8.4 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 4.9 (CH(CH₂)₂),

1

ish oil. Yield 0.24 g, 58%. IR (KBr): υ_max1640 (CO) cm⁻¹. H

3

NMR (400 MHz, CDCl₃): δ 2.26 (2H, quint, ³J = 6.8 Hz,

10.3 (CH(CH₂)₂), 21.9 (d, J_C,P= 1.2 Hz, CH_2chex), 23.1 (CH_2chex),

23.3 (CH_2chex), 23.4 (CH_2chex), 29.4 (d, ⁴J_C,P= 1.0 Hz, CH₂), 51.8 (d,

²J_C,P= 5.4 Hz, 2 × OCH₃), 112.5 (d, ¹J_C,P= 230.3 Hz, ArC), 118.1 (d,

³J_C,P= 14.8 Hz, ArC), 128.4 (ArC), 130.3 (ArC), 134.2 (d, ²J_C,P= 20.0

3

CH₂CH₂CH₂), 2.41 (2H, t, J = 7.2 Hz, CH₂CH₂CH₂), 2.87 (2H,

3

4

3

td, J_H,H= 7.2 Hz, J_H,P= 1.2 Hz, CH₂CH₂CH₂), 3.57 (6H, d, J_H,P

=

11.2 Hz, 2 × OCH₃), 7.06 (2H, t, ³J = 8.4 Hz, ArH), 7.33−7.36 (2H,

3

m, ArH), 7.42 (2H, t, J = 7.6 Hz, ArH), 7.53 (1H, t, J = 8.8 Hz,

Hz, ArC), 134.2 (ArC), 137.0 (d, J_C,P= 9.4 Hz, ArC), 137.6 (ArC)

ArH), 7.71−7.73 (2H, m, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

ppm. HRMS (ESI): MNa⁺, found 416.1161. C₂₀H₂₅ClNNaO₃P

requires 416.1153.

2

26.8 (CH₂), 27.9 (CH₂), 30.3 (CH₂), 52.6 (d, J_C,P= 6 Hz, OCH₃),

115.3 (d, J_C,F= 23 Hz, ArC), 120.0 (d, J_C,P= 226 Hz, C-sp²), 128.4

2

1

General Procedure for the Preparation of Compounds 13

and 15−18. To a cooled solution of the corresponding acetylenic α-

anilinomethylphosphonate 7−9 (1 mmol) in dry chloroform (5 mL)

3

4

(ArC), 129.2 (ArC), 129.9 (d, J_C,F= 8 Hz, ArC), 130.4 (d, J_C,P= 9

Hz, C-sp²), 132.5 (ArC), 135.7 (d, J_C,F= 4 Hz, ArC), 138.8 (ArC),

4

Q

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

3

2

4

139.5 (d, J_C,P= 14 Hz, C-sp²), 143.5 (d, J_C,P= 17 Hz, C-sp²), 162.3

Hz, J_H,P= 1.2 Hz, CH₂CH₂CH₂), 2.94 (2H, t, ³J = 7.2 Hz,

(d, J_C,F= 246 Hz, ArH), 186.4 (CO) ppm. HRMS (ESI): MNa⁺,

CH₂CH₂CH₂), 3.52 (6H, d, J_H,P= 11.6 Hz, 2 × OCH₃), 7.38−7.40

1

3

found 436.1077. C₂₂H₂₁FNNaO₄P requires 436.1084.

(2H, m, ArH), 7.45−7.47 (3H, m, ArH), 9.34 (1H, s, CHO) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ 26.2 (CH₂), 26.4 (CH₂), 30.3 (CH₂),

Dimethyl 3-Benzoyl-2-(4-chlorophenyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13e). Yellow

solid, mp 108−109 °C. Yield 0.22 g, 51%. IR (KBr): υ_max1641 (C

52.6 (d, J_C,P= 5.7 Hz, OCH₃), 119.7 (d, J_C,P= 224.4 Hz, C-sp²),

2

1

4

128.6 (ArC), 128.8 (ArC), 129.3 (ArC), 130.6 (d, J_C,P= 8.4 Hz, C-

1

3

O) cm⁻¹. H NMR (400 MHz, CDCl₃): δ 2.26 (2H, quint, J = 7.2

sp²), 137.5 (ArC), 140.3 (d, J_C,P= 13.7 Hz, C-sp²), 143.7 (d, J_C,P

=

3

2

Hz, CH₂CH₂CH₂), 2.41 (2H, t, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.87 (2H,

16.5 Hz, C-sp²), 180.6 (d, ⁴J_C,P= 1.4 Hz, CO) ppm. HRMS (ESI):

3

4

3

MNa⁺, found 342.0872. C₁₆H₁₈NNaO₄P requires 342.0866.

td, J_H,H= 7.4 Hz, J_H,P= 1.6 Hz, CH₂CH₂CH₂), 3.58 (6H, d, J_H,P

=

3

11.2 Hz, 2 × OCH₃), 7.29−7.36 (4H, m, ArH), 7.42 (2H, t, J = 7.6

Dimethyl 3-Benzoyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

[c]pyrrol-1-ylphosphonate (13a-¹⁸O). Yellowish oil. Yield 0.34 g,

86%. IR (KBr): υ_max1640 (CO¹⁸) cm⁻¹. ¹H NMR (400 MHz,

CDCl₃): δ 2.29 (2H, pent, J = 7.1 Hz,, CH₂CH₂CH₂), 2.45 (2H, t, ³J =

3

Hz, ArH), 7.53 (2H, t, J = 7.2 Hz, ArH), 7.71−7.73 (2H, m, ArH)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 26.7 (CH₂), 27.9 (CH₂), 30.2

(CH₂), 52.7 (d, ²J_C,P= 5.7 Hz, OCH₃), 119.9 (d, ¹J_C,P= 225.4 Hz, C-

sp²), 128.4 (ArC), 128.6 (ArC), 129.1 (ArC), 129.4 (ArC), 130.3 (d,

⁴J_C,P= 8.5 Hz, C-sp²), 132.6 (ArC), 134.2 (ArC), 138.2 (ArC), 138.7

3

4

7.2 Hz, CH₂CH₂CH₂), 2.92 (2H, td, J_H,H= 7.4 Hz, J_H,P= 1.5 Hz,

3

CH₂CH₂CH₂), 3.56 (6H, d, J_H,P= 11.4 Hz, 2 × OCH₃), 7.37−7.42

(ArC), 139.7 (d, ³J_C,P= 13.9 Hz, C-sp²), 143.8 (d, ²J_C,P= 16.8 Hz, C-

sp²), 186.3 (CO) ppm. HRMS (ESI): MNa⁺, found 452.0786.

C₂₂H₂₁ClNNaO₄P requires 452.0789.

(5H, m, ArH), 7.43−7.47 (2H, m, ArH), 7.52−7.57 (1H, m, ArH),

7.76 (2H, dd, J = 8.3, 1.3 Hz, ArH) ppm. ¹³C NMR (100 MHz,

2

CDCl₃): δ 26.7 (CH₂), 27.7 (CH₂), 30.1 (CH₂), 52.4 (d, J_C,P= 5.7

Hz, OCH₃), 119.7 (d, J_C,P= 225.4 Hz, C-sp²), 127.9 (ArC), 128.2

1

Dimethyl 2-(4-Methoxyphenyl)-3-(4-methylbenzoyl)-2,4,5,6-

(ArC), 128.2 (2 × ArC), 129.0 (ArC), 130.2 (d, ⁴J_C,P= 9.0 Hz, C-sp²),

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13g). Yellow-

ish oil. Yield 0.25 g, 56%. IR (KBr): υ_max1639 (CO) cm⁻¹. H

1

132.2 (ArC), 138.7 (ArC), 139.2 (d, J_C,P= 13.8 Hz, C-sp²), 139.6

3

NMR (400 MHz, CDCl₃): δ 2.26 (2H, quint, ³J = 7.2 Hz,

CH₂CH₂CH₂), 2.39 (3H, s, CH₃), 2.43 (2H, t, ³J = 7.2 Hz,

(ArC), 143.4 (d, J_C,P= 17.1 Hz, C-sp²), 186.26 (CO¹⁸)ppm.

2

HRMS (ESI): MNa⁺, found 420.1230. C₂₂H₂₂NNaO₃¹⁸OP requires

420.1227.

CH₂CH₂CH₂), 2.85−2.89 (2H, m, CH₂CH₂CH₂), 3.55 (6H, d, ³J_H,P

=

11.6 Hz, 2 × OCH₃), 6.87 (2H, d, ³J = 8.8 Hz, ArH), 7.21 (2H, d, ³J =

8.0 Hz, ArH), 7.28 (2H, d, ³J = 9.2 Hz, ArH), 7.65 (2H, d, ³J = 8.0 Hz,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 21.6 (CH₃), 26.7 (CH₂),

Dimethyl 3-(1-Iodopent-1-enyl)-2-phenyl-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (15i) (mixture

of E and Z isomers). Yellowish oil. Yield 0.28 g, 58%. ¹H NMR (400

3

2

MHz, CDCl₃): δ 0.72, 0.82 (3H, 2t, J = 7.2 Hz, J = 7.2 Hz, CH₃),

27.7 (CH₂), 30.1 (CH₂), 52.4 (d, J_C,P= 5.7 Hz, OCH₃), 55.2

3

(OCH₃), 113.2 (ArH), 119.4 (d, J_C,P= 226.1 Hz, C-sp²), 128.9

1

1.18 (2H, sext, J = 7.2 Hz, CH₂CH₃), 1.99 (2H, q, J = 7.2 Hz,

CH₂CH₂CH₃), 2.31−2.38 (2H, 2m (overlapped), CH₂), 2.64 (2H, t,

³J = 7.2 Hz, CH₂CH₂CH₂), 2.84−2.87 (2H, m, CH₂CH₂CH₂), 3.50

(6H, d, ³J_HP= 11.6 Hz, 2 × OCH₃), 5.49, 6.32 (1H, 2t, ³J = 6.8 Hz, ³J

= 7.2 Hz, CH), 7.29−7.40 (5H, m ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 13.4, 13.5 (CH₃), 21.0 (CH₂), 25.5 (CH₂), 26.8 (CH₂),

(ArC), 129.0 (ArC), 129.3 (ArC), 130.6 (d, J_C,P= 8.8 Hz, C-sp²),

4

132.4 (ArC), 136.1 (ArC), 138.3 (d, J_C,P= 14.0 Hz, C-sp²), 143.0

3

(ArC), 143.0 (d, J_C,P= 17.0 Hz, C-sp²), 159.1 (ArC), 186.1 (CO)

2

ppm. HRMS (ESI): MNa⁺, found 462.1436. C₂₄H₂₆NNaO₅P requires

462.1441.

2

30.0 (CH₂), 35.0, 38.5 (CH₂), 52.2 (d, J_HP= 5.6 Hz, 2 × OCH₃),

Dimethyl 3-(4-Ethylbenzoyl)-2-(4-methoxyphenyl)-2,4,5,6-

82.6, 90.3 (IC-sp²), 111.7 (d, J_CP= 232.3 Hz, C-sp²), 128.0 (ArC),

1

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13h). Yellow-

ish oil. Yield 0.24 g, 54%. IR (KBr): υ_max1639 (CO) cm⁻¹. H

1

128.2 (ArC), 128.7 (ArC), 131.3 (d, ³J_CP= 13.7 Hz, C-sp²), 133.7 (d,

NMR (400 MHz, CDCl₃): δ 1.24 (3H, t, ³J = 7.6 Hz, CH₂CH₃), 2.25

⁴J_CP= 9.2 Hz, C-sp²), 138.9 (ArC), 143.8 (d, J_CP= 16.7 Hz, C-sp²),

2

3

143.9, 148.8 (HC-sp²) ppm. HRMS (ESI): MNa⁺, found 508.0515.

C₂₀H₂₅INNaO₃P requires 508.0509.

(2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.46 (2H, t, J = 7.2 Hz,

3

CH₂CH₂CH₂), 2.68 (2H, q, J = 7.6 Hz, CH₂CH₃), 2.87 (2H, t, J =

7.2 Hz, CH₂CH₂CH₂), 3.55 (6H, d, ³J_H,P= 11.2 Hz, 2 × OCH₃), 6.86

(2H, d, ³J = 8.8 Hz, ArH), 7.23 (2H, d, ³J = 8.0 Hz, ArH), 7.27 (2H, d,

³J = 8.8 Hz, ArH), 7.67 (2H, d, ³J = 8.4 Hz, ArH) ppm. ¹³C NMR (100

MHz, CDCl₃): δ 15.1 (CH₃), 26.6 (CH₂), 27.7 (CH₂), 28.8 (CH₂),

Dimethyl 3-(1,4-Diiodobut-1-enyl)-2-phenyl-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (15o) (mix-

1

ture of E and Z isomers). Yellowish oil. Yield 0.29 g, 49%. H

NMR (400 MHz, CDCl₃): δ 2.34−2.39 (2H, m, CH₂CH₂CH₂), 2.60−

2

2.68 (4H, 2m, CH₂and CH₂CH₂CH₂), 2.84−2.90 (4H, m,

30.1 (CH₂), 52.4 (d, J_C,P= 5.7 Hz, OCH₃), 55.2 (OCH₃), 113.2

3

(ArC), 119.2 (d, J_C,P= 226.4 Hz, C-sp²), 127.6 (ArC), 128.9 (ArC),

1

CH₂CH₂CH₂andCH₂), 3.50 (6H, d, J_HP= 11.2 Hz, 2 × OCH₃),

3

129.4 (ArC), 130.6 (d, J_C,P= 8.7 Hz, C-sp²), 132.3 (ArC), 136.2

4

5.59, 6.25 (1H, 2t, J = 6.8 Hz, J = 7.2 Hz, CH), 7.31−7.41 (5H, m,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 1.5, 1.7 (CH₂), 25.6

(CH₂), 26.7 (CH₂), 30.0 (CH₂), 40.1 (CH₂), 52.2 (d, ²J_C,P= 5.6 Hz, 2

(ArC), 138.3 (d, ³J_C,P= 14.0 Hz, C-sp²), 143.0 (d, ²J_C,P= 17.0 Hz, C-

sp²), 149.3 (ArC), 159.0 (ArC), 186.0 (CO) ppm. HRMS (ESI):

MNa⁺, found 476.1592. C₂₅H₂₈NNaO₅P requires 476.1597.

× OCH₃), 85.4, 92.6 (CIsp²), 112.4 (d, J_C,P= 231.5 Hz, CH), 128.1

1

(ArC), 128.3 (ArC), 128.7 (ArC), 131.7 (d, J_C,P= 13.7 Hz, Csp²),

3

Dimethyl 2-(4-Chlorophenyl)-3-(4-ethylbenzoyl)-2,4,5,6-

tetrahydrocyclopenta[c]pyrrol-1-ylphosphonate (13j). Yellow-

ish oil. Yield 0.2 g, 44%. IR (KBr): υ_max1637 (CO) cm⁻¹. ¹H NMR

133.0 (d, J_C,P= 9.4 Hz, Csp²), 138.7 (ArC), 141.6, 146.0 (CHsp²),

4

143.8 (d, J_C,P= 16.9 Hz, Csp²) ppm. HRMS (ESI): MNa⁺, found

2

3

(400 MHz, CDCl₃): δ 1.25 (3H, t, J = 7.6 Hz, CH₂CH₃), 2.27 (2H,

619.9309. C₁₉H₂₂I₂NNaO₃P requires 619.9319.

quint, ³J = 7.2 Hz, CH₂CH₂CH₂), 2.46 (2H, t, ³J = 7.6 Hz,

CH₂CH₂CH₂), 2.69 (2H, q, ³J = 7.6 Hz, CH₂CH₃), 2.88 (2H, td, ³J_H,H

= 7.0 Hz, ⁴J_H,P= 1.2 Hz, CH₂CH₂CH₂), 3.57 (6H, d, ³J_H,P= 11.6 Hz, 2

Dimethyl 3-Benzoyl-2-phenyl-4,5,6,7-tetrahydro-2H-isoin-

dol-1-ylphosphonate (16a). Yellowish oil. Yield 0.25 g, 61%. IR

(KBr): υ_max1646 (CO) cm⁻¹. H NMR (400 MHz, CDCl₃): δ

1

3

1.60−1.66 (2H, m, CH₂), 1.74−1.80 (2H, m, CH₂), 2.31 (2H, t, J =

6.4 Hz, CH₂), 2.89 (2H, t, J = 6.4 Hz, CH₂), 3.51 (6H, d, ³J_H,P= 11.2

Hz, 2 × OCH₃), 7.27 (4H, br. s, ArH), 7.34−7.38 (3H, m, ArH),

7.46−7.50 (1H, m, ArH), 7.66 (2H, dd, J = 8.2; 1.6 Hz, ArH) ppm.

¹³C NMR (100 MHz, CDCl₃): δ 22.9 (CH₂), 23.0 (CH₂), 23.1 (CH₂),

23.5 (CH₂), 52.2 (d, ²J_C,P= 5.6 Hz, 2 × OCH₃), 120.7 (d, ¹J_C,P= 222.7

Hz, ArC), 127.1 (d, ³J_C,P= 14.5 Hz, ArC), 128.0 (ArC), 128.2 (ArC),

× OCH₃), 7.24 (2H, d, J = 8.4 Hz, ArH), 7.28−7.34 (4H, m, ArH),

7.67 (2H, d, ³J = 8.0 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ

15.5 (CH₂), 26.8 (CH₂), 27.9 (CH₂), 29.0 (CH₂), 30.3 (CH₂), 52.6

(d, J_C,P= 5.8 Hz, OCH₃), 119.4 (d, J_C,P= 225.7 Hz, C-sp²), 127.9

2

1

4

(ArC), 128.5 (ArC), 129.4 (ArC), 129.5 (ArC), 130.6 (d, J_C,P= 8.5

Hz, C-sp²), 134.1 (ArC), 136.1 (ArC), 138.3 (ArC), 139.1 (d, J_C,P

=

3

13.9 Hz, C-sp²), 143.8 (d, ²J_C,P= 16.0 Hz, C-sp²), 149.7 (ArC), 186.1

(CO) ppm. HRMS (ESI): MNa⁺, found 480.1100.

C₂₄H₂₅ClNNaO₄P requires 480.1102.

128.3 (ArC), 128.9 (ArC), 129.2 (ArC), 132.5 (ArC), 133.3 (d, ²J_C,P

=

3

18.8 Hz, ArC), 134.7 (d, J_C,P= 9.6 Hz, ArC), 139.0 (ArC), 139.1

4

Dimethyl 3-Formyl-2-phenyl-2,4,5,6-tetrahydrocyclopenta-

(ArC), 188.4 (d, J_C,P= 1.4 Hz, CO) ppm. HRMS (ESI): MNa⁺,

[c]pyrrol-1-ylphosphonate (13s). Yellowish oil. Yield 0.13 g, 42%.

found 432.1333. C₂₃H₂₄NNaO₄P requires 432.1335.

Dimethyl 3-Benzoyl-2-(4-methoxyphenyl)-4,5,6,7-tetrahy-

dro-2H-isoindol-1-ylphosphonate (16b). Brownish oil. Yield

IR (KBr): υ_max1666 (CO) cm⁻¹. H NMR (400 MHz, CDCl₃): δ

1

3

2.41 (2H, quint, J = 7.2 Hz, CH₂CH₂CH₂), 2.85 (2H, td, J_H,H= 7.4

R

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

0.26 g, 60%. IR (KBr): υ_max1644 (CO) cm⁻¹. ¹H NMR (400 MHz,

CDCl₃): δ 1.59−1.64 (2H, m, CH₂), 1.72−1.78 (2H, m, CH₂), 2.28

(2H, t, J = 6.0 Hz, CH₂), 2.87 (2H, t, J = 6.0 Hz, CH₂), 3.53 (6H, d,

³J_H,P= 11.2 Hz, 2 × OCH₃), 3.75 (3H, s, OCH₃), 6.77 (2H, d, J = 8.8

Hz, ArH), 7.18 (2H, d, J = 8.8 Hz, ArH), 7.36 (3H, t, J = 7.6 Hz, ArH),

7.48 (1H, t, J = 7.6 Hz, ArH), 7.65−7.67 (2H, m, ArH) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ 22.8 (CH₂), 23.0 (2 × CH₂), 23.4

CDCl₃): δ 52.7 (d, ²J_C,P= 5.5 Hz, 2 × OCH₃), 117.3 (d, ¹J_C,P= 223.8

Hz, ArC), 120.3 (ArC), 121.1 (ArC), 125.1 (ArC), 125.3 (ArC), 127.6

(d, ³J_C,P= 13.1 Hz, ArC), 128.4 (ArC), 128.5 (ArC), 129.0 (d, ³J_C,P

=

2

8.3 Hz, ArC), 129.0 (ArC), 129.7 (ArC), 131.8 (d, J_C,P= 17.4 Hz,

ArC), 132.9 (ArC), 135.1 (ArC), 137.4 (d, ³J_C,P= 1.1 Hz, ArC), 139.1

4

(ArC), 186.0 (d, J_C,P= 1.0 Hz, CO) ppm. HRMS (ESI): MNa⁺,

found 462.0640. C₂₃H₁₉ClNNaO₄P requires 462.0632.

2

Dimethyl 3-Formyl-2-(4-methoxyphenyl)-2H-isoindol-1-yl-

phosphonate (18c). Brownish solid, mp 117−118 °C. Yield 0.2 g,

56%. IR (KBr): υ_max1655 (CHO) cm⁻¹. ¹H NMR (400 MHz,

(CH₂), 52.2 (d, J_C,P= 5.5 Hz, 2 × OCH₃), 55.2 (OCH₃), 113.1

1

3

(ArC), 120.7 (d, J_C,P= 222.8 Hz, ArC), 126.7 (d, J_C,P= 14.6 Hz,

ArC), 128.2 (ArC), 129.2 (2 × ArC), 131.7 (ArC), 132.5 (ArC), 132.9

(d, ²J_C,P= 19.0 Hz, ArC), 134.7 (d, ³J_C,P= 9.6 Hz, ArC), 138.9 (ArC),

3

CDCl₃): δ 3.63 (6H, d, J_H,P= 11.6 Hz, 2 × OCH₃), 3.89 (3H, s,

159.1 (ArC), 188.5 (d, J_C,P= 1.3 Hz CO) ppm. HRMS (ESI): MH⁺,

4

OCH₃), 7.02 (2H, d, J = 8.8 Hz, ArH), 7.34−7.45 (4H, m, ArH), 8.18

(1H, d, J = 8.4 Hz, ArH), 8.41 (1H, dt, J = 8.4 Hz; 0.8 Hz, ArH), 9.55

found 440.1627. C₂₄H₂₆NO₅P requires 440.1621.

2

(1H, s, CHO) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 52.8 (d, J_C,P

=

Dimethyl 2-(4-Chlorophenyl)-3-(4-methylbenzoyl)-4,5,6,7-

tetrahydro-2H-isoindol-1-ylphosphonate (16o). Yellowish solid,

mp 99−100 °C. Yield 0.32 g, 69%. IR (KBr): υ_max1652 (CO) cm⁻¹.

¹H NMR (400 MHz, CDCl₃): δ 1.60−1.63 (2H, m, CH₂), 1.73−1.77

1

5.6 Hz, 2 × OCH₃), 55.5 (OCH₃), 113.8 (ArC), 118.5 (d, J_C,P

221.7 Hz, ArC), 120.7 (ArC), 120.9 (ArC), 126.0 (ArC), 127.3 (ArC),

127.4 (ArC), 128.9 (2 × ArC), 129.2 (ArC), 131.3 (d, ²J_C,P= 17.0 Hz,

4

ArC), 160.6 (ArC), 180.0 (d, J_C,P= 1.7 Hz, CHO) ppm. HRMS

(2H, m, CH₂), 2.27 (2H, t, J = 6.4 Hz, CH₂), 2.39 (3H, s, CH₃), 2.87

(ESI): MNa⁺, found 382.0810. C₁₈H₁₈NNaO₅P requires 382.0815.

General Procedure for the Preparation of Compounds 20

and 21. A solution of starting corresponding acetylenic aldehyde 5, 6

(1 mmol), aniline (1 mmol), and dimethylphosphite (0.121 g, 1.1

mmol) in dry dichloromethane (5 mL) was stirred at room

temperature. When the consumption of starting aldehyde was

observed by TLC, 10 mol % copper(I) iodide (19.05 mg, 0.1

mmol) was added. When the full completion of the reaction was

observed by TLC (after 1−4 h), the solvent was evaporated under

reduced pressure, and the residue was puriﬁed by ﬂash column

chromatography eluting with hexane−ethyl acetate mixtures.

3

(2H, t, J = 6.0 Hz, CH₂), 3.55 (6H, d, J_H,P= 11.2 Hz, 2 × OCH₃),

7.19−7.27 (6H, m, ArH), 7.60 (2H, d, J = 8.4 Hz, ArH) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ 21.7 (CH₃), 22.8 (CH₂), 22.9 (CH₂),

23.0 (CH₂), 23.6 (CH₂), 52.2 (d, ²J_C,P= 5.5 Hz, 2 × OCH₃), 120.5 (d,

3

¹J_C,P= 222.6 Hz, ArC), 126.8 (d, J_C,P= 14.5 Hz, ArC), 128.2 (ArC),

2

129.1 (ArC), 129.4 (ArC), 129.5 (ArC), 133.4 (d, J_C,P= 18.7 Hz,

ArC), 134.0 (ArC), 134.8 (d, ³J_C,P= 9.4 Hz, ArC), 136.1 (ArC), 137.7

(ArC), 143.8 (ArC), 187.9 (d, ⁴J_C,P= 1.1 Hz, CO) ppm. HRMS (ESI):

MNa⁺, found 480.1096. C₂₄H₂₅ClNNaO₄P requires 480.1102.

Dimethyl 3-(1-Iodopent-1-enyl)-2-(4-methoxyphenyl)-

4,5,6,7-tetrahydro-2H-isoindol-1-ylphosphonate (17k). Yellow-

ish oil. Yield 0.12 g, 22%. Compound exists as the geometrical isomers,

Dimethyl 6,7-Diphenyl-5,6-dihydro-1,6-naphthyridin-5-yl-

phosphonate (20a). Brownish solid, mp 146−147 °C. Yield 0.23

1

which were not isolated due to the same R_f. H NMR (400 MHz,

1

3

g, 58%. H NMR (400 MHz, DMSO-d₆): δ 3.56 (3H, d, J_H,P= 10.4

CDCl₃): δ 0.79; 0.84 (3H, 2t, J = 7.2 Hz, J = 7.2 Hz, CH₃), 1.25−1.33

(2H, m, CCHCH₂CH₂), 1.73−1.76 (4H, 2m (overlap.), 2 ×

CH_2chex), 2.03 (2H, q, J = 7.2 Hz, CCHCH₂CH₂), 2.42 (2H, t, J =

5.6 Hz, CH_2chex), 2.81 (2H, br. s, CH_2chex), 3.49−3.55 (6H, 2m

(overlap.), 2 × OCH₃), 3.82; 3.83 (3H, 2s, OCH₃), 5.58; 6.37 (1H, 2t,

J = 6.8 Hz, J = 7.2 Hz, CH), 6.86 (2H, d, J = 8.8 Hz, ArH), 7.18 (2H,

d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.4; 13.6

(CH₃), 21.1; 21.6 (CH₂), 22.1 (CH₂), 22.9; 23.0 (CH₂), 23.1 (CH₂),

Hz, OCH₃), 3.69 (3H, d, ³J_H,P= 10.8 Hz, OCH₃), 5.94 (1H, d, ¹J_H,P

=

2

18.8 Hz, CH), 6.67 (1H, br. s, C_spH), 6.91 (1H, t, J = 7.2 Hz, ArH),

7.05 (2H, d, J = 7.6 Hz, ArH), 7.15 (2H, t, J = 7.6 Hz, ArH), 7.24−

7.33 (4H, m, ArH), 7.57 (2H, d, J = 6.8 Hz, ArH), 7.63 (1H, d, J = 6.0

Hz, ArH), 8.73 (1H, br. s, ArH) ppm. ¹³C NMR (100 MHz, DMSO-

d₆): δ 52.9 (d, ²J_C,P= 4.1 Hz, OCH₃), 53.0 (d, ²J_C,P= 4.2 Hz, OCH₃),

62.0 (d, ¹J_C,P= 158.9 Hz, CH), 103.6 ( C_spH), 112.7 (ArC), 122.8 (3

4

2

× ArC), 127.5 (ArC), 128.4 (ArC), 128.6 (2 × ArC), 129.0 (ArC),

23.4 (CH₂), 35.1; 38.5 (CH₂), 52.0 (d, J_C,P= 5.4 Hz, 2 × OCH₃),

3

4

134.5 (ArC), 136.5 (ArC), 146.0 (ArC), 146.6 (d, J_C,P= 6.7 Hz,

55.3; 55.3 (OCH₃), 82.8; 90.5 (2d, J_C,P= 1.6 Hz, J_C,P= 1.6 Hz, IC

3

+

1

3

2

ArC), 148.0 (ArC), 151.5 ( C_sp) ppm. HRMS (ESI): MNa , found

_sp2), 113.0 (ArC), 114.4 (d, J_C,P= 197.7 Hz, ArC), 119.8 (d, J_C,P

14.3 Hz, ArC), 129.9 (ArC), 131.4 (ArC), 133.0 (d, J_C,P= 18.8 Hz,

=

2

415.1178. C₂₂H₂₁N₂NaO₃P requires 415.1182.

3

Dimethyl 6-(4-Methoxyphenyl)-7-phenyl-5,6-dihydro-1,6-

naphthyridin-5-ylphosphonate (20b). Yellow oil. Yield 0.26 g,

61%. ¹H NMR (400 MHz, DMSO-d₆): δ 3.56 (3H, d, ³J_H,P= 10.4 Hz,

ArC), 137.4 (d, J_C,P= 10.7 Hz, ArC), 145.1; 149.5 (C_sp2H), 159.1;

159.2 (ArC) ppm. HRMS (ESI): MH⁺, found 530.0959. C₂₂H₃₀INO₄P

requires 530.0952.

3

OCH₃), 3.61 (3H, s, OCH₃), 3.68 (3H, d, J_H,P= 10.4 Hz, OCH₃),

Dimethyl 3-(1,4-Diiodobut-1-enyl)-2-phenyl-4,5,6,7-tetrahy-

dro-2H-isoindol-1-ylphosphonate (17l). Yellowish oil. Yield 0.51

g, 83%. Compound exists as the geometrical isomers, which were not

isolated due to the same R_f. ¹H NMR (400 MHz, CDCl₃): δ 1.76 (4H,

2br. s (overlap.), 2 × CH_2chex), 2.46 (2H, br. s, CH_2chex), 2.65 (2H, q, J

= 6.8 Hz, CCHCH₂CH₂), 2.83 (2H, br. s, CH_2chex), 2.93 (2H, t, J =

6.8 Hz, CCHCH₂CH₂), 3.46−3.52 (6H, 2m (overlap.), 2 ×

OCH₃), 5.69; 6.31 (1H, 2t, J = 6.8 Hz, J = 6.8 Hz, CH), 7.28−7.30

(2H, m, ArH), 7.37−7.38 (3H, m, ArH) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ 22.0; 22.2 (CH₂), 22.8; 22.9 (CH₂), 23.0 (CH₂), 23.2; 23.3

5.73 (1H, d, ¹J_H,P= 19.6 Hz, CH), 6.51 (1H, br. s, C_spH), 6.73 (2H, d,

2

J = 8.8 Hz, ArH), 7.01 (2H, d, J = 8.4 Hz, ArH), 7.23−7.32 (4H, m,

ArH), 7.55 (3H, d, J = 6.4 Hz, ArH), 8.45 (1H, br. s, ArH) ppm. ¹³C

2

NMR (100 MHz, DMSO-d₆): δ 52.9 (d, J_C,P= 2.0 Hz, OCH₃), 53.0

2

1

(d, J_C,P= 2.1 Hz, OCH₃), 55.0 (OCH₃), 62.7 (d, J_C,P= 161.8 Hz,

4

2

CH), 111.5 ( C_spH), 113.9 (ArC), 121.6 (ArC), 124.6 (d, J_C,P= 1.2

Hz, ArC), 127.6 (ArC), 128.4 (ArC), 128.6 (ArC), 129.1 (ArC), 134.5

3

(d, J_C,P= 4.4 Hz, ArC), 136.6 (ArC), 140.3 (d, J_C,P= 7.3 Hz, ArC),

3

2

146.4 (ArC), 148.7 (ArC), 151.5 ( C_sp), 155.3 (ArC) ppm. HRMS

(ESI): MNa⁺, found 445.1282. C₂₃H₂₃N₂NaO₄P requires 445.1288.

2

(CH₂), 36.6 (CH₂), 40.0 (CH₂), 52.0 (d, J_C,P= 5.5 Hz, 2 × OCH₃),

85.5; 92.7 (2d, ⁴J_C,P= 1.6 Hz, ⁴J_C,P= 1.5 Hz, IC _sp2), 114.8 (d, ¹J_C,P

=

Dimethyl 6-Phenyl-7-propyl-5,6-dihydro-1,6-naphthyridin-

1

3

5-ylphosphonate (20c). Brownish oil. Yield 0.17 g, 52%. H NMR

227.4 Hz, ArC), 120.3 (d, J_C,P= 14.2 Hz, ArC), 128.0; 128.1 (ArC),

2

(400 MHz, DMSO-d₆): δ 0.83 (3H, t, J = 7.2 Hz, CH₃), 1.46 (2H,

sexst., J = 7.2 Hz, CH₂), 2.11−2.19 (1H, m, CHH), 2.23−2.31 (1H, m,

CHH), 3.56 (3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.66 (3H, d, ³J_H,P= 10.4

128.2; 128.4 (ArC), 128.9 (ArC), 133.3 (d, J_C,P= 18.7 Hz, ArC),

3

136.4 (d, J_C,P= 10.7 Hz, ArC), 138.4; 138.5 (ArC), 143.2; 147.1

(C_sp2H) ppm. HRMS (ESI): MNa⁺, found 633.9469. C₂₀H₂₄

I₂NNaO₃P requires 633.9475.

Hz, OCH₃), 5.56 (1H, d, ²J_H,P= 18.4 Hz, CH), 6.13 (1H, br. s, C_spH),

2

7.13 (1H, t, J = 7.2 Hz, ArH), 7.24 (2H, d, J = 8.0 Hz, ArH), 7.32−

7.36 (2H, m, ArH), 7.43−7.50 (2H, m, ArH), 8.45 (1H, br. s, ArH)

ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 13.6 (CH₃), 20.7 (CH₂),

Dimethyl 3-Benzoyl-2-(4-chlorophenyl)-2H-isoindol-1-yl-

phosphonate (18b). Yellowish solid, mp 57−58 °C. Yield 0.19 g,

44%. IR (KBr): υ_max1649 (CO) cm⁻¹. ¹H NMR (400 MHz,

2

3

35.0 (CH₂), 52.7 (d, J_C,P= 7.2 Hz, OCH₃), 53.0 (d, J_C,P= 6.9 Hz,

CDCl₃): δ 3.64 (6H, d, J_H,P= 11.6 Hz, 2 × OCH₃), 7.09 (2H, m,

4

2

ArH), 7.23−7.27 (1H, m, ArH), 7.33−7.41 (4H, m, ArH), 7.45 (2H, t,

J = 7.6 Hz, ArH), 7.58 (1H, t, J = 7.6 Hz, ArH), 7.77−7.79 (2H, m,

ArH), 8.23 (1H, d, J = 8.8 Hz, ArH) ppm. ¹³C NMR (100 MHz,

OCH₃), 63.6 (d, ¹J_C,P= 161.0 Hz, CH), 109.7 ( C_spH), 120.6 (ArC),

124.2 (ArC), 124.2 (ArC), 128.9 (ArC), 129.4 (ArC), 134.2 (d, ³J_C,P

5.0 Hz, ArC), 145.9 (d, J_C,P= 5.7 Hz, ArC), 148.4 (2 × ArC), 151.7

=

3

S

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

3

+

2

( C_sp) ppm. HRMS (ESI): MH , found 359.1526. C₁₉H₂₃N₂O₃P

requires 359.1519.

Dimethyl 6-(4-Methoxyphenyl)-7-((tetrahydro-2H-pyran-2-

yloxy)methyl)-5,6-dihydro-1,6-naphthyridin-5-ylphosphonate

(20h). Yellowish oil. Yield 0.22 g, 48%. Compound exists as the

Dimethyl 7-Cyclopropyl-6-phenyl-5,6-dihydro-1,6-naph-

1

diastereomers, which were not isolated due to the same R_f. H NMR

thyridin-5-ylphosphonate (20d). Brownish solid, mp 144−145

1

(400 MHz, DMSO-d₆): δ 1.38−1.47 (4H, 2m (overlap.), 2 × CH₂),

°C. Yield 0.22 g, 63%. H NMR (400 MHz, DMSO-d₆): δ 0.71−0.75

1.52−1.69 (2H, m, CH₂), 3.42−3.48 (2H, m, CH₂), 3.59; 3.62 (3H,

(2H, m, CH(CH₂)₂), 0.80−0.84 (2H, m, CH(CH₂)₂), 1.33 (1H, p, J =

2d, ³J_H,P= 10.8 Hz, ³J_H,P= 10.8 Hz, OCH₃), 3.65; 3.65 (3H, 2d, ³J_H,P

=

3

6.4 Hz, CH(CH₂)₂), 3.60 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.65 (3H,

10.4 Hz, ³J_H,P= 10.4 Hz, OCH₃), 3.73 (3H, s, OCH₃), 3.93; 3.97 (1H,

2d, J = 6.8 Hz, J = 6.8 Hz, CCHHO), 4.12; 4.18 (1H, 2d, J = 13.6

Hz, J = 13.6 Hz, CCHHO), 4.40; 4.69 (1H, 2t, J = 3.2 Hz, J = 3.2

3

2

d, J_H,P= 10.4 Hz, OCH₃), 5.64 (1H, d, J_H,P= 18.8 Hz, CH), 5.90

2

(1H, br. s, C_spH), 7.06 (1H, br. s, ArH), 7.12−7.14 (1H, m, ArH),

7.32−7.37 (4H, m, ArH), 7.45 (1H, d, J = 6.0 Hz, ArH), 8.35 (1H, br.

2

s, ArH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 8.4 (CH(CH₂)₂),

Hz, O-CH-O), 5.42; 5.46 (1H, 2d, J_H,P= 6.8 Hz, J_H,P= 6.8 Hz,

2

PCH), 6.09; 6.15 (1H, 2br. s, C_spH), 6.91; 6.91 (2H, 2d, J = 9.2 Hz, J

10.9 (CH(CH₂)₂), 14.2 (CH(CH₂)₂), 53.0 (d, J_C,P= 6.9 Hz, 2 ×

OCH₃), 62.5 (d, ¹J_C,P= 159.3 Hz, CH), 104.2 ( C_spH), 120.3 (ArC),

4

2

= 8.8 Hz, ArH), 7.09 (1H, J = 5.6 Hz, ArH), 7.24; 7.25 (2H, 2d, J = 8.8

Hz, J = 8.8 Hz, ArH), 7.42 (1H, d, J = 7.6 Hz, ArH), 8.31 (1H, br. s,

ArH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 18.6; 18.6 (CH₂),

24.8; 24.9 (CH₂), 29.8 (CH₂), 52.8; 53.0 (2d, ²J_C,P= 7.0 Hz, ²J_C,P= 6.8

123.8 (ArC), 123.8 (ArC), 128.8 (ArC), 129.1 (ArC), 134.1 (d, ³J_C,P

=

3

4.3 Hz, ArC), 146.0 (d, J_C,P= 5.5 Hz, ArC), 148.4 (ArC), 150.9

(ArC), 151.8 ( C_sp) ppm. HRMS (ESI): MH , found 357.1369.

C₁₉H₂₂N₂O₃P requires 357.1363.

3

+

2

Hz, POCH₃), 53.0; 53.1 (2d, J_C,P= 6.5 Hz, J_C,P= 6.7 Hz, POCH₃),

55.2 (OCH₃), 60.6; 60.9 (CH₂), 63.0 (d, ¹J_C,P= 160.0 Hz, CH), 64.3;

Dimethyl 7-Cyclopropyl-6-(4-methoxyphenyl)-5,6-dihydro-

4

2

1,6-naphthyridin-5-ylphosphonate (20e). Brownish solid, mp

65.1 (CCH₂O), 96.0; 97.6 (O-CH-O), 107.9; 108.2 ( C_spH),

1

111−112 °C. Yield 0.27 g, 59%. H NMR (400 MHz, DMSO-d₆): δ

114.1; 114.2 (ArC), 118.8 (ArC), 120.9 (ArC), 126.3 (ArC), 126.7

3

0.62−0.82 (4H, m, CH(CH₂)₂), 1.22−1.24 (1H, m, CH(CH₂)₂), 3.59

(3H, d, ³J_H,P= 10.4 Hz, OCH₃), 3.63 (3H, d, ³J_H,P= 10.4 Hz, OCH₃),

3.73 (3H, s, OCH₃), 5.49 (1H, d, ²J_H,P= 17.6 Hz, CH), 5.78 (1H, br. s,

(ArC), 134.3; 134.4 (2d, J_C,P= 2.7 Hz, J_C,P= 2.9 Hz ArC), 138.6;

138.7 (2d, ³J_C,P= 5.3 Hz, ³J_C,P= 5.3 Hz, ArC), 145.2; 145.6 (2d, ³J_C,P

=

2.2 Hz, ³J_C,P= 2.0 Hz, C_sp), 148.6 (ArC), 151.2; 151.3 (2d, J_C,P= 3.1

3

2

3

2

C_spH), 6.91 (2H, d, J = 8.4 Hz, ArH), 7.04 (1H, d, J = 8.4 Hz, ArH),

Hz, J_C,P= 3.2 Hz, ArC), 156.7; 156.8 (ArC) ppm. HRMS (ESI):

7.29 (2H, d, J = 8.0 Hz, ArH), 7.39−7.52 (1H, m, ArH), 8.36 (1H, br.

s, ArH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 7.7 (CH(CH₂)₂),

10.7 (CH(CH₂)₂), 14.2 (CH(CH₂)₂), 53.0 (d, ²J_C,P= 4.5 Hz, OCH₃),

53.0 (d, J_C,P= 4.7 Hz, OCH₃), 55.2 (OCH₃), 63.2 (d, J_C,P= 159.4

Hz, CH), 102.0 ( C_spH), 114.1 (ArC), 120.2 (ArC), 126.4 (ArC),

MH⁺, found 461.1837. C₂₃H₃₀N₂O₆P requires 461.1836.

Dimethyl 2-(4-Methoxyphenyl)-3-phenyl-1,2-dihydrobenzo-

[b][1,6]naphthyridin-1-ylphosphonate (21a). Yellow solid, mp

188−190 °C. Yield 0.27 g, 48%. ¹H NMR (300 MHz, CDCl₃): δ 3.63

(3H, d, ³J_HP= 10,5 Hz, OCH₃), 3.65 (3H, s, OCH₃), 3.76 (3H, d, ³J_HP

= 10,8 Hz, OCH₃), 5.50 (1H, d, ¹J_HP= 20.1 Hz, C₁H), 6.66 (2H, d, ³J

2

1

4

2

3

128.7 (ArC), 134.1 (d, J_C,P= 4.8 Hz, ArC), 139.2 (d, J_C,P= 5.1 Hz,

3

2

= 9.0 Hz, ArH), 6.80 (1H, s, C₄H), 7.49 (2H, d, J = 9.0 Hz, ArH),

ArC), 148.3 (ArC), 151.7 (ArC), 152.3 ( C_sp), 156.4 (ArC) ppm.

7.25−7.29 (3H, m, ArH), 7.41 (1H, td, ³J = 7.3 Hz, ⁴J = 0.9 Hz, ArH),

7.63−7.67 (3H, m, ArH), 7.71 (1H, d, ³J = 8.1 Hz, ArH), 7.81 (1H, d,

HRMS (ESI): MH⁺, found 387.1462. C₂₀H₂₄N₂O₄P requires

387.1468.

3

⁴J_HP= 3.3 Hz, ArH), 8.06 (1H, d, J = 8.4 Hz, ArH) ppm. ¹³C NMR

Dimethyl 6-Phenyl-5,6-dihydro-1,6-naphthyridin-5-yl-

phosphonate (20f). Brownish oil. Yield 0.16 g, 50%. ¹H NMR

2

(75 MHz, CDCl₃): δ 53.3 (d, J_CP= 7.3 Hz, OCH₃), 53.6 (d, J_CP

=

3

6.5 Hz, OCH₃), 55.2 (OCH₃), 65.0 (¹J_CP= 163.5 Hz, CH), 110.2 (C₄-

sp²), 114.0 (ArC), 120.7 (ArC), 125.4 (ArC), 125.4 (ArC), 127.2 (⁴J_CP

= 2.4 Hz, ArH), 127.6 (ArC), 127.8 (ArC), 128.3 (ArC), 128.4 (ArC),

128.9 (ArC), 129.1 (ArC), 130.0 (ArC), 134.2 (d, ³J_CP= 9.0 Hz, ArC),

136.5 (ArC), 140.7 (d, ³J_CP= 5.7 Hz, ArC), 147.8 (ArC), 151.8 (ArC),

156.2 (C₃-sp²) ppm. HRMS (ESI): MH⁺, found 473.1626.

C₂₇H₂₆N₂O₄P requires 473.1625.

(400 MHz, DMSO-d₆): δ 3.52 (3H, d, J_H,P= 10.4 Hz, OCH₃), 3.56

(3H, d, ³J_H,P= 10.4 Hz, OCH₃), 5.90 (1H, d, J = 6.4 Hz, C_spH), 6.08

2

(1H, d, ²J_H,P= 13.6 Hz, CH), 7.04 (1H, t, J = 7.2 Hz, ArH), 7.08−7.10

2

(2H, m, ArH, C_spH), 7.26 (2H, d, J = 8.0 Hz, ArH), 7.36 (2H, t, J =

7.6 Hz, ArH), 7.53 (1H, d, J = 7.2 Hz, ArH), 8.33 (1H, br. s, ArH)

ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 52.8 (d, J_C,P= 7.3 Hz,

2

1

OCH₃), 52.9 (d, J_C,P= 7.2 Hz, OCH₃), 57.6 (d, J_C,P= 152.6 Hz,

CH), 106.4 (d, ³J_C,P= 1.4 Hz, C_spH), 117.2 (d, J_C,P= 1.4 Hz, ArC),

4

2

Dimethyl 3-Butyl-2-phenyl-1,2-dihydrobenzo[b][1,6]-

naphthyridin-1-ylphosphonate (21b). Yellow solid, mp 149−151

°C. Yield 0.2 g, 48%. ¹H NMR (300 MHz, CDCl₃): δ 0.82 (3H, t, ³J =

7.2 Hz, CH₃), 1.24−1.35 (2H, m, CH₂), 1.50−1.60 (2H, m, CH₂),

119.6 (ArC), 120.7 (ArC), 121.8 (ArC), 129.0 (ArC), 134.3 (d, ³J_C,P

=

3

2

2.2 Hz, ArC), 134.6 (d, J_C,P= 6.0 Hz, ArC), 144.2 ( C_sp), 148.6

(ArC), 151.4 (ArC) ppm. HRMS (ESI): MH⁺, found 317.1046.

C₁₆H₁₈N₂O₃P requires 317.1050.

3

2.18−2.39 (2H, m, CH₂), 3.60 (3H, d, J_HP= 10,5 Hz, OCH₃), 3.72

3

1

4

Dimethyl 6-Phenyl-7-((tetrahydro-2H-pyran-2-yloxy)-

methyl)-5,6-dihydro-1,6-naphthyridin-5-ylphosphonate (20g).

Brownish oil. Yield 0.22 g, 51%. Compound exists as the

diastereomers, which were not isolated due to the same R_f. ¹H

NMR (400 MHz, DMSO-d₆): δ 1.34−1.52 (4H, 2m (overlap.), 2 ×

CH₂), 1.53−1.68 (2H, m, CH₂), 3.23−3.36 (2H, m, CH₂), 3.60; 3.63

(3H, d, J_HP= 10,5 Hz, OCH₃), 5.30 (1H, dd, J_HP= 19.2 Hz, J_HH=

0.6 Hz, C₁H), 6.34 (1H, s, C₄H), 7.13−7.19 (1H, m, ArH), 7.30−7.37

4

(5H, m, ArH), 7.57−7.66 (2H, m, ArH), 7.70 (1H, d, J_HP= 3.0 Hz,

3

ArH), 7.97 (1H, d, J = 8.4 Hz, ArH) ppm. ¹³C NMR (75 MHz,

CDCl₃): δ 13.7 (CH₃), 22.2 (CH₂), 30.0 (CH₂), 33.5 (CH₂), 53.2 (d,

2

²J_CP= 7.2 Hz, OCH₃), 53.5 (d, J_CP= 7.2 Hz, OCH₃), 65.7 (¹J_CP

=

3

161.4 Hz, CH), 108.3 (C₄-sp²), 119.3 (ArC), 124.9 (ArC), 125.3

(ArC), 125.4 (ArC), 127.0 (⁴J_CP= 2.1 Hz, ArC), 127.5 (ArC), 127.8

(ArC), 129.1 (ArC), 129.8 (ArC), 133.6 (d, ³J_CP= 8.4 Hz, ArC), 146.2

(3H, 2d, J_H,P= 8.8 Hz, J_H,P= 8.8 Hz, OCH₃), 3.66; 3.67 (3H, 2d,

³J_H,P= 10.4 Hz, J_H,P= 10.4 Hz, OCH₃), 4.02; 4.06 (1H, 2d, J = 8.4

3

Hz, J = 8.4 Hz, CCHHO), 4.21; 4.27 (1H, 2d, J = 13.6 Hz, J = 14.0

(d, J_CP= 4.8 Hz, ArC), 147.8 (ArC), 152.1 (ArC), 153.1 (C₃-sp²)

3

Hz, CCHHO), 4.43; 4.71 (1H, 2br. s, O-CH-O), 5.57; 5.62 (1H,

2

ppm. HRMS (ESI): MH⁺, found 423.1835. C₂₄H₂₈N₂O₃P requires

423.1838.

2

2d, J_H,P= 10.8 Hz, J_H,P= 11.2 Hz, PCH), 6.29 (1H, br. s, C_spH),

7.13−7.16 (2H, 2m (overlap.), 2 × ArH), 7.27−7.30 (2H, m, ArH),

7.33−7.37 (2H, m, ArH), 7.48 (1H, d, J = 6.8 Hz, ArH), 8.40 (1H, br.

s, ArH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ 18.6; 18.7 (CH₂),

24.8; 24.9 (CH₂), 29.8; 29.9 (CH₂), 52.9; 53.1 (2d, ²J_C,₂_P= 7.1 Hz, ²J_C,P

Dimethyl 3-Butyl-2-(4-methoxyphenyl)-1,2-dihydrobenzo-

[b][1,6]naphthyridin-1-ylphosphonate (21c). Yellow solid, mp

1

48−50 °C. Yield 0.18 g, 40%. H NMR (300 MHz, CDCl₃): δ 0.81

2

3

= 7.0 Hz, OCH₃), 53.2; 53.2 (2d, J_C,P= 3.0 Hz, J_C,P= 3.1 Hz,

(3H, t, J = 7.2 Hz, CH₃), 1.20−1.35 (2H, m, CH₂), 1.47−1.57 (2H,

3

OCH₃), 60.6; 61.0 (CH₂), 62.6 (d, ¹J_C,P= 160.9 Hz, PCH), 64.1; 65.0

m, CH₂), 2.09−2.30 (2H, m, CH₂), 3.58 (3H, d, J_HP= 10,5 Hz,

4

3

2

(CCH₂O), 96.0; 97.7 (O-CH-O), 110.3; 110.5 ( C_spH), 119.8

OCH₃), 3.70 (3H, d, J_HP= 10,8 Hz, OCH₃), 3.77 (3H, s, OCH₃),

(ArC), 121.3 (ArC), 123.7; 124.2 (ArC), 124.4; 124.6 (ArC), 129.0;

5.19 (1H, dd, ¹J_HP= 19.0 Hz, ⁴J_HH= 0.6 Hz, C₁H), 6.20 (1H, s, C₄H),

3

129.0 (ArC), 134.5 (d, J_C,P= 3.8 Hz, ArC), 144.6; 145.0 (2d, J_C,P

1.7 Hz, J_C,P= 1.9 Hz, ArC), 145.5; 145.7 (2d, J_C,P= 5.6 Hz, J_C,P

5.6 Hz, C_sp), 148.7 (ArC), 151.0 (ArC) ppm. HRMS (ESI): MH ,

found 431.1728. C₂₂H₂₈N₂O₅P requires 431.1730.

=

6.83 (2H, d, J = 9.3 Hz, ArH), 7.25−7.35 (3H, m, ArH), 7.55−7.67

3

=

(3H, m, ArH), 7.97 (1H, d, J = 8.4 Hz, ArH) ppm. ¹³C NMR (75

3

+

2

MHz, CDCl₃): δ 13.7 (CH₃), 22.1 (CH₂), 29.9 (CH₂), 33.5 (CH₂),

2

53.2 (d, J_CP= 6.6 Hz, OCH₃), 53.2 (d, J_CP= 7.2 Hz, OCH₃), 55.4

T

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(OCH₃), 64.9 (¹J_CP= 160.6 Hz, CH), 106.1 (C₄-sp²), 114.2 (ArC),

119.2 (ArC), 124.6 (ArC), 126.9 (⁴J_CP= 2.1 Hz, ArC), 127.5 (ArC),

127.6 (2 × ArC), 129.7 (ArC), 133.5 (d, ³J_CP= 8.4 Hz, ArC), 139.2 (d,

³J_CP= 4.3 Hz, ArC), 147.7 (ArC), 152.3 (ArC), 153.8 (C₃-sp²), 157.6

(ArC), 127.1 (ArC), 127.4 (ArC), 127.5 (ArC), 127.5 (ArC), 130.1

3

(ArC), 133.8 (d, J_CP= 7.1 Hz, ArC), 142.1 (ArC), 151.8 (C₃-sp²),

2

160.3 (d J_CF= 244.8 Hz, ArC) ppm. HRMS (ESI): MH⁺, found

425.1424. C₂₃H₂₃FN₂O₃P requires 425.1425.

(ArC) ppm. HRMS (ESI): MH⁺, found 453.1941. C₂₅H₃₀N₂O₄P

requires 453.1938.

Dimethyl 2-(4-Chlorophenyl)-3-cyclopropyl-1,2-

dihydrobenzo[b][1,6]naphthyridin-1-ylphosphonate (21h).

Yellow solid, mp 78−80 °C. Yield 0.22 g, 50%.¹H NMR (300 MHz,

CDCl₃): δ 0.79−0.92 (3H, m, CH(CH₂)₂), 0.99−1.05 (1H, m,

CH(CH₂)₂), 1.29−1.38 (1H, m, CH(CH₂)₂), 3.61 (3H, d, ³J_HP= 10.5

Dimethyl 3-Butyl-2-(4-ﬂuorophenyl)-1,2-dihydrobenzo[b]-

[1,6]naphthyridin-1-ylphosphonate (21d). Yellow oil. Yield 0.24

1

3

g, 52%. H NMR (300 MHz, CDCl₃): δ 0.82 (3H, t, J = 7.5 Hz,

3

CH₃), 1.19−1.39 (2H, m, CH₂), 1.54 (2H, quint, J = 7.8 Hz, CH₂),

Hz, OCH₃), 3.74 (3H, d, ³J_HP= 10.8 Hz, OCH₃), 5.31 (1H, d, ¹J_HP

=

3

2.12−2.31 (2H, m, CH₂), 3.60 (3H, d, J_HP= 10,5 Hz, OCH₃), 3.71

3

1

18.3 Hz, C₁H), 6.04 (1H, s, C₄H), 7.26−7.39 (5H, m, ArH), 7.57−

7.66 (2H, m, ArH), 7.69 (1H, d, ⁴J_HP= 3.3 Hz, ArH), 7.81 (1H, d, ³J =

8.4 Hz, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 9.0 (CH(CH₂)₂),

11.9 (CH(CH₂)₂), 14.7 (CH(CH₂)₂), 53.3 (d, ²J_CP= 7.4 Hz, OCH₃),

53.8 (d, ²J_CP= 6.9 Hz, OCH₃), 64.5 (d, ¹J_CP= 161.3 Hz, C₁H), 102.2

(C₄-sp²), 119.7 (ArC), 125.0 (ArC), 126.3 (ArC), 126.7 (ArC), 127.5

(d, J_CP= 3.3 Hz, ArC), 129.1 (ArC), 129.9 (ArC), 130.4 (ArC), 133.6

(3H, d, J_HP= 10,8 Hz, OCH₃), 5.21 (1H, d, J_HP= 19.2 Hz, C₁H),

6.27 (1H, s, C₄H), 6.97−7.03 (2H, m, ArH), 7.29−7.37 (3H, m, ArH),

7.57−7.66 (2H, m, ArH), 7.70 (1H, d, ⁴J_HP= 3.6 Hz, ArH), 7.95 (1H,

d, ³J = 8.7 Hz, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 13.6 (CH₃),

22.2 (CH₂), 29.9 (CH₂), 33.5 (CH₂), 53.3 (d, ²J_CP= 7.3 Hz, OCH₃),

53.4 (d, ²J_CP= 7.4 Hz, OCH₃), 64.8 (¹J_CP= 161.6 Hz, CH), 107.6 (C₄-

sp²), 115.9 (d ²J_CF= 22.5 Hz, ArC), 119.2 (ArC), 124.9 (ArC), 127.0

(ArC), 127.5 (ArC), 127.6 (d, ³J_CF= 8.5 Hz, ArC), 127.8 (ArC), 129.8

(ArC), 133.6 (d, ³J_CP= 8.1 Hz, ArC), 142.2 (ArC), 147.7 (ArC), 152.0

3

(d, J_CP= 8.1 Hz, ArC), 144.6 (d, J_CP= 4.2 Hz, ArC), 147.5 (ArC),

151.8 (ArC), 154.8 (C₃-sp²) ppm. HRMS (ESI): MH⁺, found

441.1147. C₂₃H₂₃ClN₂O₃P requires 441.1129.

1

(ArC), 153.0 (C₃-sp²), 160.4 (d J_CF= 244.7 Hz, ArC) ppm. HRMS

(ESI): MH⁺, found 457.1441 C₂₄H₂₇ClN₂O₃P requires 457.1442.

Dimethyl 2-(4-Methoxyphenyl)-3-propyl-1,2-dihydrobenzo-

[b][1,6]naphthyridin-1-ylphosphonate (21e). Yellow solid, mp

Synthesis of (E)-4-Methoxy-N-{[2-(phenylethynyl)quinolin-3-

yl]methylene}aniline (22). A mixture of 2-phenylethynylquinoline-

3-carbaldehyde 6a (100 mg, 0.389 mmol), 4-methoxyaniline (47.84

mg, 0.389 mmol), and 3 Å MS (100 mg) was stirred in dry chloroform

(5 mL). When completion of the reaction was observed by TLC, the

solvent was evaporated under reduced pressure, and the residue was

puriﬁed by ﬂash column chromatography eluting with hexane−ethyl

acetate mixtures to aﬀord 0.16 g (88%) of yellow solid. Mp 175−176

°C. IR (KBr): υ_max2219 (CC) cm⁻¹. ¹H NMR (400 MHz, CDCl₃):

δ 3.89 (3H, s, OCH₃), 7.02 (2H, d, ³J = 8.9 Hz, ArH), 7.40 (2H, d, ³J

= 8.9 Hz, ArH), 7.42−7.47 (3H, m, ArH), 7.61 (1H, ddd, ³J = 8.1 and

6.9 Hz, ⁴J = 1.1 Hz, ArH), 7.70−7.72 (2H, m, ArH), 7.80 (1H, ddd, ³J

1

47−49 °C. Yield 0.3 g, 68%. H NMR (400 MHz, CDCl₃): δ 0.87

3

(3H, t, J = 7.6 Hz, CH₃), 1.54−1.56 (2H, m, CH₂), 2.11−2.15 and

2.20−2.23 (2H, 2m, CH₂), 3.58 (3H, d, ³J_HP= 10,4 Hz, OCH₃), 3.70

(3H, d, ³J_HP= 10,4 Hz, OCH₃), 3.76 (3H, s, OCH₃), 5.18 (1H, d, ¹J_HP

3

= 19.2 Hz, C₁H), 6.19 (1H, s, C₄H), 6.82 (2H, d, J = 9.0 Hz, ArH),

3

7.25 (2H, d, J = 8,4 Hz, ArH), 7.31 (1H, t, J = 8,4 Hz, ArH), 7.57

(1H, t, ³J = 8,4 Hz, ArH), 7.62 (1H, d, ³J = 8.1 Hz, ArH), 7.65 (1H, d,

⁴J = 3.6 Hz, ArH), 7.92 (1H, d, ³J = 8.4 Hz, ArH) ppm. ¹³C NMR (100

2

MHz, CDCl₃): δ 13.8 (CH₃), 21.1 (CH₂), 36.01 (CH₂), 53.3 (d, J_CP

= 7.3 Hz, OCH₃), 53.4 (d, ²J_CP= 7.3 Hz, OCH₃), 55.4 (OCH₃), 64.5

(¹J_CP= 161.6 Hz, CH), 106.4 (C₄-sp²), 114.3 (ArC), 124.6 (ArC),

126.9 (J_CP= 2.1 Hz, ArC), 127.5 (ArC), 127.6 (2 × ArC), 127.8

(ArC), 129.6 (ArC), 133.4 (J_CP= 8.5 Hz, ArC), 139.3 (⁴J_CP= 4.6 Hz,

ArC), 147.9 (ArC), 152.3 (ArC), 153.4 (C₃-sp²), 157.6 (ArC) ppm.

HRMS (ESI): MH⁺, found 439.1791. C₂₄H₂₈N₂O₄P requires

439.1787.

4

3

= 8.4 and 6.9 Hz, J = 1.4 Hz, ArH), 7.96 (1H, d, J = 7.9 Hz, ArH),

3

8.18 (1H, d, J = 8.5 Hz, ArH), 9.06 (1H, s, ArH), 9.28, s, CHN)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ 55.5 (OCH₃), 86.68 (C_sp),

94.55 (C_sp), 114.2 (ArC), 121.8 (ArC), 122.6 (ArC), 127.2 (ArC),

127.7 (ArC), 128.6 (ArC), 128.8 (ArC), 129.2 (ArC), 129.5 (ArC),

130.2 (ArC), 131.3 (ArC), 132.2 (ArC), 134.3 (ArC), 143.6 (ArC),

144.6 (ArC), 149.0 (ArC), 154.8 (ArC), 158.9 (ArC) ppm. HRMS

(ESI): MH⁺, found 363.1500. C₂₅H₁₉N₂O requires 363.1497.

Dimethyl 3-Cyclopropyl-2-(4-methoxyphenyl)-1,2-

dihydrobenzo[b][1,6]naphthyridin-1-ylphosphonate (21f). Yel-

1

low solid, mp 60−61 °C. Yield 0.29 g, 67%. H NMR (300 MHz,

CDCl₃): δ 0.72−0.83 (3H, m, CH(CH₂)₂), 1.00−1.06 (1H, m,

CH(CH₂)₂), 1.28−1.35 (1H, m, CH(CH₂)₂), 3.60 (3H, d, ³J_HP= 10.8

Hz, OCH₃), 3.74 (3H, d, ³J_HP= 10.5 Hz, OCH₃), 3.78 (3H, s, OCH₃),

5.29 (1H, d, ¹J_HP= 18.6 Hz, C₁H), 5.91 (1H, s, C₄H), 6.85 (2H, d, ³J =

9.0 Hz, ArH), 7.32 (1H, t, ³J = 7.2 Hz, ArH), 7.38 (2H, d, ³J = 9.0 Hz,

ArH), 7.55−7.66 (3H, m, ArH), 7.92 (1H, d, ³J = 8.1 Hz, ArH) ppm.

¹³C NMR (75 MHz, CDCl₃): δ 8.4 (CH(CH₂)₂), 11.5 (CH(CH₂)₂),

Synthesis of Dimethyl (4-Methoxyphenylamino)[2-(pent-1-

ynyl)quinolin-3-yl]methylphosphonate (23). To a solution of 2-

(pent-1-ynyl)quinoline-3-carbaldehyde 6c (100 mg, 0.448 mmol), 4-

methoxyaniline (55.15 mg, 0.448 mmol), and dimethylphoshite (54.21

mg, 0.493 mmol) was added gold(III) bromide (19.58 mg, 0.0448

mmol). When the completion of the reaction was observed by TLC,

the solvent was evaporated under reduced pressure, and the residue

was puriﬁed by ﬂash column chromatography eluting with hexane−

ethyl acetate mixtures to aﬀord 0.16 g (83%) of yellow solid. Mp 118−

2

14.7 (CH(CH₂)₂), 53.2 (d, J_CP= 7.4 Hz, OCH₃), 53.7 (d, J_CP= 6.3

1

Hz, OCH₃), 55.4 (OCH₃), 65.0 (d, J_CP= 160.2 Hz, C₁H), 99.7 (C₄-

sp²), 114.1 (ArC), 119.5 (ArC), 124.6 (ArC), 126.7 (ArC), 127.4

1

119 °C. IR (KBr): υ_max3298 (NH), 2211 (CC) cm⁻¹. H NMR

3

(ArC), 127.4 (2 × ArC), 129.8 (ArC), 133.4 (d, J_CP= 8.3 Hz, ArC),

(400 MHz, CDCl₃): δ 1.12 (3H, t, ³J = 7.2 Hz, CH₃), 1.76 (2H, sext,

3

139.3 (d, J_CP= 4.5 Hz, ArC), 147.5 (ArC), 152.4 (ArC), 156.0 (C₃-

³J = 7.2 Hz, CH₂), 2.59 (2H, t, ³J = 7.2 Hz, CH₂), 3.44 (3H, d, ³J_HP

=

sp²), 157.4 (ArC) ppm. HRMS (ESI): MH⁺, found 437.1633.

C₂₄H₂₆N₂O₄P requires 437.1625.

3

10.8 Hz, OCH₃), 3.65 (3H, s, OCH₃), 3.88 (3H, d, J_HP= 10.8 Hz,

OCH₃), 4.81 (1H, br. s, NH), 5.57 (1H, d, ¹J_HP= 24.4 Hz, CH), 6.60

(2H, d, ³J = 8.8 Hz, ArH), 6.67 (2H, d, ³J = 8.8 Hz, ArH), 7.47 (1H, t,

³J = 7.2 Hz, ArH), 7.66 (1H, t, ³J = 7.2 Hz, ArH), 7.73 (1H, d, ³J = 8.0

Hz, ArH), 8.05 (1H, d, ³J = 8.4 Hz, ArH), 8.33 (1H, d, ³J_HP= 2.8 Hz,

ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 13.6 (CH₃), 21.6 (CH₂),

Dimethyl 3-Cyclopropyl-2-(4-ﬂuorophenyl)-1,2-

dihydrobenzo[b][1,6]naphthyridin-1-ylphosphonate (21g).

Yellow solid, mp 60−61 °C. Yield 0.28 g, 67%. ¹H NMR (300

MHz, CDCl₃): δ 0.77−0.89 (3H, m, CH(CH₂)₂), 1.03−1.10 (1H, m,

CH(CH₂)₂), 1.27−1.36 (1H, m, CH(CH₂)₂), 3.63 (3H, d, ³J_HP= 10.8

Hz, OCH₃), 3.76 (3H, d, ³J_HP= 10.5 Hz, OCH₃), 5.30 (1H, dd, ¹J_HP

=

1

2

21.8 (CH₂), 52.6 (d, J_CP= 152.6 Hz, CH), 53.7 (d, J_CP= 7.3 Hz,

4

18.3 Hz, J = 0.6 Hz, C₁H), 6.04 (1H, s, C₄H), 7.00−7.06 (2H, m,

ArH), 7.34−7.39 (1H, m, ArH), 7.46−7.48 (2H, m, ArH), 7.59−7.67

(2H, m, ArH), 7.71 (1H, d, ⁴J_HP= 3.6 Hz, ArH), 8.00 (1H, d, ³J = 8.4

Hz, ArH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 8.7 (CH(CH₂)₂), 11.8

(CH(CH₂)₂), 14.8 (CH(CH₂)₂), 53.3 (d, ²J_CP= 7.4 Hz, OCH₃), 53.8

(d, ²J_CP= 6.7 Hz, OCH₃), 64.8 (d, ¹J_CP= 161.0 Hz, C₁H), 100.4 (C₄-

sp²), 115.8 (d ²J_CF= 22.5 Hz, ArC), 119.6 (ArC), 125.0 (ArC), 126.6

OCH₃), 54.1 (d, J_CP= 6.8 Hz, OCH₃), 55.6 (OCH₃), 78.6 (Csp³),

2

97.0 (Csp³), 114.8 (ArC), 114.9 (ArC), 127.0 (d, ⁴J_CP= 2.9 Hz, ArC),

127.1 (ArC), 127.7 (ArC), 128.6 (ArC), 130.2 (ArC), 130.9 (ArC),

3

134.9 (ArC), 139.3 (d, J_CP= 15.3 Hz, ArC), 143.5 (ArC), 147.2

(ArC), 152.8 (ArC) ppm. HRMS (ESI): MH⁺, found 439.1789.

C₂₄H₂₈N₂O₄P requires 439.1781.

U

dx.doi.org/10.1021/jo501011u | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(c) Ma, Y.; Wang, J.-G.; Wang, B.; Li, Z.-M. J. Mol. Model. 2011, 17,

1899. (d) Wang, B.; Miao, Z. W.; Wang, J.; Chen, R. Y.; Zhang, X. D.

Amino Acids 2008, 35, 463.

(5) (a) Ding, Q.; Ye, Y.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72, 5439.

(b) Ding, Q.; Wang, B.; Wu, J. Tetrahedron 2007, 63, 12166. (c) Ding,

Q.; Wang, B.; Wu, J. Tetrahedron Lett. 2007, 49, 8599.

ASSOCIATED CONTENT

■

S

* Supporting Information

Copies of ¹H and ¹³C NMR spectra of the reported

compounds. This material is available free of charge via the

Internet at http://pubs.acs.org.

(6) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron. Lett. 1975,

16, 4467.

AUTHOR INFORMATION

Corresponding Author

*Phone: +370 5 219 31 95, +370 5 219 31 87. Fax: +370 5 233

09 87. E-mail: inga.cikotiene@chf.vu.lt.

■

(7) Delort, E.; Klotz, P.; Salem, B.; Suffert, J. Org. Lett. 2003, 5, 2307.

(8) Das, A.; Lin, M. Y.; Liu, R. S. J. Am. Chem. Soc. 2006, 128, 9340.

(9) (a) Kabachnik, M. I.; Medved, T. Y. Dokl. Akad. Nauk SSSR

1952, 83, 689. (b) Fields, E. K. J. Am. Chem. Soc. 1952, 74, 1528.

(10) (a) Kudzin, Z. H.; Kudzin, M. H.; Drabowicz, J.; Stevens, C. V.

Curr. Org. Chem. 2011, 15, 2015. (b) Cherkasov, R. A.; Galkin, V. I.

Russ. Chem. Rev. 1998, 67, 857.

Notes

The authors declare no competing ﬁnancial interest.

(11) Some other bases (K₃PO₄, K₂CO₃, NaOCH₃, and DABCO)

were tested, but potassium tert-butanoate proved to be the most

eﬀective. Gold(III) bromide gave excellent results, so other sources of

gold(III) were not investigated.

ACKNOWLEDGMENTS

The research was funded by the European Social Fund under

the Global Grant measure (Grant No. VP1-3.1-SMM-07-K-01-

■

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Formation of condensed 1 H-pyrrol-2-ylphosphonates and 1,2-dihydropyridin- 2-ylphosphonates via Kabachnik-fields reaction of acetylenic aldehydes and subsequent 5-exo-dig or 6-endo-dig cyclizations

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