Rhodium(i)-catalyzed vinylation/[2 + 1] carbocyclization of 1,6-enynes with α-diazocarbonyl compounds

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PAPER

Rhodium(I)-Catalyzed Vinylation/[2+1] Carbocyclization of 1,6-

Enynes with -Diazocarbonyl Compounds†

Junmin Huang,^§Xinwei Hu,^§Fengjuan Chen, Jiao Gui, and Wei Zeng *

Received 00th January 201x,

Accepted 00th January 201x

DOI: 10.1039/x0xx00000x

A sequential Rh(I)-catalyzed vinylation/[2+1]carbocyclization of between enynes and diazo compounds has been

developed. This transformation features a wide range of enynes and acceptor/acceptor diazo compounds, providing easy

access to versatile vinyl-substituted azabicyclo[3.1.0]hexanes with a broad tolerance of functional groups.

www.rsc.org/

assemble alkenylbicyclo[3.1.0]hexanes by employing Ru(II)

catalysts, in which the scope of diazo compounds was very

limited (Scheme 1a).²²Subsequently, Snapper found Grubbs’s

Introduction

Cycloaddition reactions of unsaturated hydrocarbons provides

a powerful platform for assembling complex molecules.¹

Among them, 1,n-enynes (n = 5-7) have emerged as important

synthons to access diverse fused ring systems through redox

metal-catalysis that are inaccessible using traditional organic

reactions.²In this regards, much progress about enyne-based

[m+n+o] cycloadditions with various coupling partners such as

Ru(II)-catalyzed coupling-cyclization enynes with diazoacetate

led to the formation of cyclopropyl-substituted cycloolefines

through tandem enyne metathesis/cyclopropanation process

(

Scheme 1b).²³More recently, Liu reported that Au(I)/Rh(II)-

catalyzed cycloaddition reaction of enynes with diazo

compounds could efficiently furnish complex tetrahydro-1H-

cyclopropa[b]naphthalenes (Scheme 1c).²⁴Thus it can be seen

that the coupling reaction between enynes and diazo

compounds would afford structurally diverse polycyclic

molecules employing different catalytical systems.

As the continuation of our interest in exploring diazo

compound-based cross-coupling reactions,²⁵we herein

disclose a Rh(I)-catalyzed coupling–cyclization of enynes with

diazo compounds for rapidly assembling diverse functionalized

vinyl-substituted bicyclo[3.1.0]hexanes, in which diazo

compounds could be extend to acceptor/acceptor or

donor/acceptor diazo compounds (Scheme 1d).

alkynes,³alkenes,⁴arenes,⁵aldehydes,⁶silanes,⁷azirines,⁸N-

hydroxyanilines,⁹silylboranes,¹⁰carbon monoxide

and

11

others, ¹²have been achieved for rapidly furnishing polycyclic

compounds. Nevertheless, in the light of the fact that

structurally diverse polycyclic systems are commonly

encountered in many natural products and pharmaceutical

molecules,¹³developing novel cycloaddition of enynes with

diverse coupling partners for constructing versatile fused

polycycles is always desirable.

It is well-known that the cross-coupling reactions involved

diazo compounds provide a powerful tool to form C-X bonds (X

= C, N, etc). To date, the couplings of diazo compounds with

alkanes,¹⁴arenes,¹⁵alcohols,¹⁶amines,¹⁷amides,¹⁸alkynes,¹⁹

and alkenes,²⁰etc. have been widely explored to make

particular molecules. Unfortunately, the coupling-cyclization

between enynes and diazo compounds are rarely reported

possibly due to that metal carbenes could independently

undergo [2+1] cycloaddition with alkynyl and alkenyl moiety of

enynes to form three-member cycles.²¹Up to now, this

transformation has been pioneeringly developed by Dixneuf to

*Key Laboratory of Functional Molecular Engineering of Guangdong Province,

Guangdong Engineering Research Center for Green Fine Chemicals, School of

Chemistry and Chemical Engineering, South China University of Technology,

Guangzhou 510641, China

Fax: (+86)-20-2223-6337; e-mail: zengwei@scut.edu.cn

^§The two authors contributed equally to this work.

†

Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra,

Scheme 1. Cycloadditions of enynes with diazo compounds

under different catalytical systems

mass of the compounds and crystallographic data of compound (Z)-3-1a in CIF.

CCDC 1887226. For ESI and crystallographic data in CIF or other electronic format

see DOI: 10.1039/x0xx00000x

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DOI: 10.1039/C9OB01028A

Results and discussion

Our initial efforts focused on screening various metal catalysts

(5 mol %), which could possibly enable the coupling-cyclization

^aAll the reactions were performed using diazo compound

1a (0.4 mmol) and enyne 2a (0.4 mmol) in the presence

of catalysts (5 mol %) with ligand (10 mol %) in solvent

(2.0 mL) at 100 ^oC for 12 h under Ar in a sealed reaction

tube. Followed by flash chromatography on SiO₂;

of



-diazo-



-ketoester

(1a

)

with N-allyl-N-propargyl-4-

methylbenzenesulfonamide (2a) in the presence of PPh₃(10

mol %) in 1,2-dichloroethane (DCE) at 100 ^oC under Ar

atmosphere for 12 h (Table 1, entries 1-6). Gratifyingly, we

soon found that [Rh(COD)Cl]₂could produce the

vinylation/[2+1]carbocyclization product 3-1a in 35% yield (E/Z

= 14 : 21) (entry 6), and the other catalysts including Pd(PPh₃)₄,

Ni(COD)₂, Ru₃(CO)₁₂, [Rh(C₂H₄)₂Cl]₂and [Rh(COD)(OH)]₂did not

efficiently enhance the coupling reaction at all (compare

entries 1-5 with 6). Moreover, the structures of (Z)-3-1a was

already unambiguously confirmed by its single crystal X-ray

analysis.²⁶Subsequently, the solvent screening was further

performed employing [Rh(COD)Cl]₂as catalysts, and toluene

proved to be the most suitable solvent (entries 6-9 vs 10).

^bIsolated yield ^cThe E/Z ratios were calculated based

.

on the isolated yields.

With the optimized reaction conditions known, various

diazo compounds were first employed to react with enyne 2a

.

As shown in Table 2 -diazo- -alkylketoesters could smoothly

,





couple with 2a to produce 1-fatty acyl-1-ethoxycarbonyl-vinyl-

substiuted azabicyclo[3.1.0]hexanes 3-1a and 3-2b in 85% and

79% yields, respectively. Meanwhile,

also tolerated this reaction system, and afforded versatile 1-

arylacyl-1-ethoxycarbonylvinyl-substituted azabicyclo[3.1.0]

hexanes 3-1c 3-1l in 48-91% yields. Among them, -diazo-

(4-chlorophenyl)ketoester, -diazo- -(4-bromophenyl)

ketoester, -diazo- -(4- methylphenyl)ketoester and -diazo-

-(4-methoxyphenyl)ketoester could be efficiently converted

into the corresponding polycycles (3-1e 3-1g and 3-1j) in

good to excellent yields (66-91%). In comparison, the electron-

deficient -diazo- -(4-flurophenyl)ketoester and -diazo- -(4-

-diazo--arylketoesters

Finally, different types of ligands (L₁-L₇) were evualated in

order to improve the reaction conversion. It was found that

the electron-deficient monodentate ligands (L₃and L₄vs L₁and

L₂) did not enable this reaction to occur at all (entries 10 and

11 vs 12 and 13). To our satisfaction, switching 1,2-

‒



-











bis(diphenylphosphino)ethane

(DPPE)

to

1,3-



bis(diphenylphosphino)propane (DPPP), which has a slightly

larger bite-angle and better flexibility range,²⁷significantly

increased the yield of 3-1a to 84% (entries 10-15 vs 16). It

should be noted that the transformation could not occur in the

absence of ligands (entry 17).

‒









trifluromethylphenyl)ketoester led to inferior transformations,

affording 58% and 48% yied of 3-1d and 3-1l, respectively.

Moreover, the steric hindrance of the ortho-substituent on the

Table 1. Optimization of the reaction parameters ^a



-phenyl ring of diazo compounds inhibited the reaction

conversion to some degree, and produced 70% and 48% yields

of 3-1i and 3-1k 3-1g vs 3-1i 3-1j vs 3-1k), respectively. To our

satisfactory, -diazo- -(2-naphthyl)ketoester, -diazo- -(2-

thiophyl)ketoester, -diazo phosphonate, -diazo diketones,

and even -diazo diester could also react with 2a to assemble

the desired products 3-1m 3-1s in acceptable yields (8-60%

yields). On the contrary, donor/acceptor diazo compounds

made the transformation very sluggish. For examples, the

electron-rich ethyl 2-diazo-2-phenylacetate and 2-diazo-2-(4-

methyl)phenylacetate only gave 15% yield of 3-1t and 5% yield

of 3-1u, respectively, and electron-deficient ethyl 2-diazo-2-(4-

(trifluoromethyl)phenyl)acetate (1v) did not afford the desired

product at all. Meanwhile, the simple diazo compounds such

(

,











yield (%) ^b

‒

entry

catalyst

ligand solvent

(E/Z) ^c

1

2

3

4

5

6

7

8

Pd(PPh₃)₄

Ni(COD)₂

Ru₃(CO)₁₂

L₁

L₂

L₃

L₄

L₅

L₆

L₇

--

DCE

0

[Rh(C₂H₄)₂Cl]₂

[Rh(COD)(OH)]₂

[Rh(COD)Cl]₂

trace

35(14/21)

trace

24(11/13)

38(16/22)

22(8/14)

0

DCE

CH₃CN

dioxane

PhCF₃

toluene

as acceptor diazo compound ethyl

-diazoacetate (1w) and

donor diazo compound diazomethyltrimethylsilane (1x) could

not undergo the coupling-cyclization with enyne 2a to afford

the corresponding products, and 2a was almost recovered

completely.

9

10

11

12

13

14

15

16

17

0

Table 2. Scope of diazo compounds ^{a, b}

toluene 84(41/43)

toluene

0

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azabicyclo[4.1.0]heptanes 3-2e (84%) and 3-2f (51%),

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DOI: 10.1039/C9OB01028A

respectively. It is gratifying that the coupling-cyclization could

still be extended to diethyl 2-allyl-2-(prop-2-yn-1-yl)malonate

and electron-deficient 1,6-enyne [N-(prop-2-yn-1-yl)-N-

tosylacrylamide], affording 44% yield of 3-2g and 37% yield of

3-2h, respectively. However, when N-Ts-N,N-dipropynylamine

(1,6-diyne) coupled with 2-diazo-3-oxo-3-phenyl-propionic acid

ethyl ester under the reaction system, the unexpected [2+2+2]

product N-tosylisoindoline 3-2i could be obtained in 25% yield.

Unfortunately, the 1,6-enynes containing the steric linker (2k

)

or internal alkyne (2l) could not react with diazo compound 1a

to produce the desired products possibly due to the steric

factors.

Table 3. Scope of enynes^{a, b}

^aAll the reactions were performed using diazo compound

1a (0.4 mmol) and enynes 2 (0.40 mmol) with

[Rh(COD)Cl]₂(5 mol %) and dppp (10 mol %) in

^aAll the reactions were performed using diazo

compounds (0.4 mmol) and 1,6-enyne 2a (0.40

mmol) with [Rh(COD)Cl]₂5 mol %) and dppp (10

1

(

o

toluene (2.0 mL) at 100 C for 12 h under Ar in a sealed

mol %) in toluene (2.0 mL) at 100 C for 12 h under

reaction tube. Followed by flash chromatography on

Ar in a sealed reaction tube. Followed by flash

b

SiO₂; Isolated yield. ^cThe E/Z ratios were calculated

c

chromatography on SiO₂

;

^bIsolated yield. The E/Z

based on the isolated yields. ^dThe E/Z ratios were

calculated based on the ¹H NMR spectrum.

ratios were calculated based on the isolated yields.

1

^dThe E/Z ratios were calculated based on the H

NMR spectrum.

The synthetic applications of this transformation (Scheme 2

indicated that the ketone moiety of the vinyl-functionalized

beta-ketoacetate ( )-3-1a could be selectively reduced by

)

To further investigate the scope of enynes, the coupling-

cyclization of diazo compound 1a with different types of

enynes was further systemically evaluated. As shown in Table

Z

NaBH₄to furnish beta-hydroxy-alpha-methylene-acetate (Z)-

4

(44%). Moreover, the bridgehead Csp³-Csp³bond of

azabicyclo[3.1.0]hexane moiety could also be easily cleavaged

3

, besides the terminal alkene-substituted 1,6-enynes, internal

olefin-containing 1,6-enynes such as 1-phenyl-, 1-methyl-, or

2-methyl-substituted 1,6-enynes and even cyclohexene-

containing 1,6-enyne all tolerated this reaction system,

assembling the vinyl-functionalized azabicyclo[3.1.0]hexanes

by aqueous HBr to give piperidin-3-ol derivative (Z)-5 (61% ).

3-2a

‒ 3-2d in 16-85% yields. Moreover, N-homoallyl-

substituted proparglyamide and N-homopropargyl-substituted

allylamide could also smoothly couple with 1a to produce

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Scheme 2. Synthetic applications

In conclusion, we have successfully developed a highly step

and atom economical Rh(I)-catalyzed coupling-cyclization of

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DOI: 10.1039/C9OB01028A

enynes with diazo compounds, affording 1-vinyl-substituted

To elucidate the possible reaction mechanism, the terminal azabicyclo[3.1.0]hexanes with tolerance of various enynes and

deuterated alkyne d1-2a (90% D) was first treated with

diazoacetate 1a, and 81 atom % D was incorporated into





-

acceptor/acceptor diazo compounds. Moreover, the utility of

this method demonstrated that these azabicycloalkanes could

position of , -unsaturated ester d1-3-1a, demonstrating that be further converted into versatile nitrogen heterocycles.

the terminal carbon of alkynes was involved in the cross-

coupling with rhodium carbenes (Scheme 3a). Meanwhile,

when the terminal deuterated alkene d2-2a (45% D) was

employed to cyclize with 1a, 37 atom % D was detected at the

6-position of azabicyclo[3.1.0]hexane (d2-3-1a), which

indicated that the olefinic double bond was involved in the

[2+1] carbocyclization (Scheme 3b).

Experimental Section

General Information

General Methods. All reactions were carried out in flame-dried

sealed tubes with magnetic stirring. Unless otherwise noted, all

experiments were performed under argon atmosphere. Solvents were

treated with 4 Å molecular sieves or sodium and distilled prior to use.

Purifications of reaction products were carried out by flash

chromatography using silica gel (400 – 630 mesh). Infrared Spectra

(IR) are reported as wavelength number (cm-1). Infrared spectra

were recorded by preparing a KBr pellet containing the title

compounds. ¹H NMR and ¹³C NMR spectra were recorded with

tetramethylsilane (TMS) as internal standard at ambient temperature

(400 MHz for ¹H NMR and 101 MHz for ¹³C NMR). Chemical

shifts are reported in parts per million (ppm) and coupling constants

are reported as Hertz (Hz). Splitting patterns are designated as

singlet (s), broad singlet (bs), doublet (d), triplet (t). Splitting

patterns that could not be interpreted or easily visualized are

designated as multiple (m). High resolution mass spectra (HRMS)

were recorded on an IF-TOF spectrometer (Micromass). Gas

chromatograph mass spectra were obtained with a SHIMADZU

model GCMS-QP5000 spectrometer. All the α-diazo-β-ketoesters

(1a-1v, see SI for the details)²⁸and 1,6-enynes (2a-2k, see SI for the

details)^{29, 30}were prepared according to the previous literature.

Scheme 3. Preliminary mechanistic studies

On the basis of the above-mentioned experiments, we have

proposed a plausible mechanism in Scheme 4. The initial

reaction of

rhodium carbene complex



-diazo acetate (

1

) with Rh(I) catalysts affords

with the extrusion of a N₂

A

molecule. Subsequently, the coupling reaction between Rh(I)-

carbene and alkyne led to the formation of

rhodiumcyclobutene B ²²

which could further undergoes a

ring-opening reaction to generate intermediate . Finally, the

intramolecular cascade cycloaddition/reductive elimination of

rhodium carbene with alkene produced the desired 1-vinyl-

azabicyclo[3.1.0]hexanes

General Procedure for the Synthesis of Azabicyclo[3.1.0]hexanes

Derivatives (3-1a~3-1u) and (3-2a~3-2i)

A

,

C

To an oven-dried sealed tube charged with [Rh(COD)Cl]₂(5 mol %),

dppp (10 mol %), alpha-diazo compounds (0.4 mmol) and 1,6-

enynes (0.4 mmol), toluene (2.0 mL) were added under argon

C

o

3

.

atmosphere. The reaction mixture was allowed to stir at 100 C for

12 h, the corresponding solution was diluted by ethyl acetate (5.0

mL), filtrated and concentrated to get the crude products. The

desired compounds were purified by column chromatography using

petroleum ether / ethyl acetate as eluent.

Ethyl

(E)-3-oxo-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)butanoate (3-1a). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg,

0.4 mmol), and purified by column chromatography to give white

solid (62.0 mg, 41%). R_f(petroleum ether/ethyl acetate = 5:1) 0.34;

m.p. 126.0-128.0 ^oC. ¹H NMR (400 MHz, CDCl₃) δ 7.66 (d, J = 7.9

Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 6.47 (s, 1H), 4.21 (q, J = 7.1 Hz,

2H), 3.54 (q, J = 14.2, 9.4 Hz, 2H), 3.08 (q, J = 9.4, 3.6 Hz, 1H),

2.86 (d, J = 9.4 Hz, 1H), 2.44 (s, 3H), 2.37 (s, 3H), 1.74 – 1.67 (m,

1H), 1.26 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 5.3 Hz, 1H), 1.10 – 1.05 (m,

1H); ¹³C NMR (101 MHz, CDCl₃) δ 201.5, 164.2, 146.1, 143.9,

135.0, 132.9, 129.8, 127.6, 61.4, 51.1, 48.9, 31.4, 28.9, 28.0, 21.5,

17.6, 14.1; HR-MS (ESI) calcd for [M + H]⁺: C₁₉H₂₃NO₅S: 378.1370,

Scheme 4. The possible reaction mechanism

Conclusions

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found: 378.1364; IR (KBr): 3029, 2955, 1716, 1597, 1478, 1162, solid (114.2 mg, 65%). R_f(petroleum ether/ethyl aceta_Vte_iew=_A5_rt:_ic1_l)_{e O}0_n.3_lin3_e;

820 cm^-1.

m.p. 134.0-137.0 C; H NMR (400 MHz, CDCl₃) δ 7.71 (d, J = 4.8

Hz, 1H), 7.46 (d, J = 3.7 Hz, 1H), 7.42 (s, 2H), 7.18 (d, J = 8.0 Hz,

2H), 7.09 – 7.05 (m, 1H), 6.64 (s, 1H), 4.07 (m, 2H), 3.43 (d, J = 9.3

Hz, 1H), 3.26 (d, J = 9.3 Hz, 1H), 2.85 – 2.74 (m, 2H), 2.34 (s, 3H),

1.74 – 1.61 (m, 1H), 1.15 (t, J = 5.3 Hz, 1H), 1.06 (q, J = 7.4 Hz,

4H); ¹³C NMR (101 MHz, CDCl₃) δ 186.4, 164.3, 147.2, 144.5,

143.7, 135.5, 134.4, 132.1, 131.8, 129.7, 128.5, 127.5, 61.5, 50.5,

48.8, 29.1, 28.0, 21.6, 17.9, 14.0; HR-MS (ESI) calcd for [M + H]⁺:

C₂₄H₂₆NO₅S: 440.1526, found: 440.1515; IR (KBr): 3032, 2982,

1719, 1669, 1597, 1475, 1164, 813 cm^-1.

o

1

DOI: 10.1039/C9OB01028A

Ethyl

(Z)-3-oxo-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)butanoate (3-1a). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg,

0.4 mmol), and purified by column chromatography to give white

solid (65.0 mg, 43%). R_f(petroleum ether/ethyl acetate = 5:1) 0.33;

m.p. 126.0-128.0 ^oC, ¹H NMR (400 MHz, CDCl₃) δ 7.66 (d, J = 7.9

Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 6.47 (s, 1H), 4.21 (q, J = 7.1 Hz,

2H), 3.54 (q, J = 14.2, 9.4 Hz, 2H), 3.08 (q, J = 9.4, 3.6 Hz, 1H),

2.86 (d, J = 9.4 Hz, 1H), 2.44 (s, 3H), 2.37 (s, 3H), 1.74 – 1.67 (m, Ethyl

1H), 1.26 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 5.3 Hz, 1H), 1.10 – 1.05 (m, azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1d). The title compound

1H); ¹³C NMR (101 MHz, CDCl₃) δ 201.5, 164.2, 146.1, 143.9, was

prepared from ethyl 2-diazo-3-(4-fluorophenyl)-3-

(Z)-2-(4-fluorobenzoyl)-3-(3-tosyl-3-

135.0, 132.9, 129.8, 127.6, 61.4, 51.1, 48.9, 31.4, 28.8, 28.0, 21.5, oxopropanoate (1d) (94.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-

17.6, 14.1; HR-MS (ESI) calcd for [M + H]⁺: C₁₉H₂₃NO₅S: 378.1370, (prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and

found: 378.1364; IR (KBr): 3029, 2955, 1716, 1597, 1478, 1162, purified by column chromatography to give yellow oil liquid (106.3

820 cm^-1.

mg, 58%). R_f(petroleum ether/ethyl acetate = 5:1) 0.33; H NMR

(400 MHz, CDCl₃) δ 7.81 (dd, J = 8.4, 5.5 Hz, 2H), 7.34 (d, J = 8.0

Hz, 2H), 7.09 (d, J = 9.6 Hz, 4H), 6.66 (s, 1H), 4.11 – 3.96 (m, 2H),

3.43 (d, J = 9.3 Hz, 1H), 3.24 (d, J = 9.3 Hz, 1H), 2.83 (q, J = 9.3,

3.7 Hz, 1H), 2.59 (d, J = 9.3 Hz, 1H), 2.33 (s, 3H), 1.72 – 1.60 (m,

1H), 1.21 – 1.09 (m, 1H), 1.01 (t, J = 7.1 Hz, 4H); ¹³C NMR (101

1

Ethyl

(E)-3-oxo-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)pentanoate (3-1b). The title compound was prepared

from ethyl 2-diazo-3-oxopentanoate (1b) (68.0 mg, 0.4 mmol) and

N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6

mg, 0.4 mmol), and purified by column chromatography to give

yellow oily liquid (59.0 mg, 38%). R_f(petroleum ether/ethyl acetate

= 5:1) 0.34; ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H),

7.27 (d, J = 8.0 Hz, 2H), 6.39 (d, J = 7.4 Hz, 1H), 4.17 (m, 2H), 3.59

– 3.34 (m, 2H), 3.10 – 2.82 (m, 1H), 2.73 (d, J = 9.4 Hz, 1H), 2.66 –

2.42 (m, 2H), 2.37 (s, 3H), 1.72 – 1.59 (m, 1H), 1.29 (t, J = 7.2 Hz,

1H), 1.18 (t, J = 7.1 Hz, 3H), 1.05 (t, J = 7.3 Hz, 3H), 0.98 (t, J = 7.2

1

MHz, CDCl₃) δ 192.7, 166.1(d, J = 255.0 Hz, J_CF), 164.3, 147.5,

143.7, 133.5(d, J = 2 Hz, J_CF), 132.0, 131.9, 131.8, 129.6, 127.4,

3

2

116.1(d, J = 22.0 Hz, J_CF), 61.5, 50.8, 48.8, 29.1, 27.9, 21.5, 17.9,

13.9; HR-MS (ESI) calcd for [M + H]⁺: C₂₄H₂₅FNO₅S: 458.1432,

found: 458.1417; IR (KBr): 3064, 2981, 1716, 1597, 1505, 1167,

817 cm^-1.

Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 205.0, 164.3, 145.7, 143.9, Ethyl

134.7, 132.6, 129.8, 127.6, 61.4, 50.9, 48.9, 37.3, 28.7, 27.8, 21.6, azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1e). The title compound

17.5, 14.1, 7.86; HR-MS (ESI) calcd for [M + H]⁺: C₂₀H₂₆NO₅S: was

prepared from ethyl 3-(4-chlorophenyl)-2-diazo-3-

392.1526, found: 392.1514; IR (KBr): 3026, 2982, 1725, 1698, 1633, oxopropanoate (1e) (111.0 mg, 0.4 mmol) and N-allyl-4-methyl-N-

(E)-2-(4-chlorobenzoyl)-3-(3-tosyl-3-

1456, 1165, 816 cm^-1.

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and

purified by column chromatography to give yellow oil liquid (28.1

mg, 15%). R_f(petroleum ether/ethyl acetate = 4:1) 0.34; H NMR

Ethyl

(Z)-3-oxo-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

1

yl)methylene)pentanoate (3-1b). The title compound was prepared

from ethyl 2-diazo-3-oxopentanoate (1b) (68.0 mg, 0.4 mmol) and

N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6

mg, 0.4 mmol), and purified by column chromatography to give

yellow oily liquid (65.3 mg, 41%). R_f(petroleum ether/ethyl acetate

= 5:1) 0.33; ¹H NMR (400 MHz, CDCl₃) δ 7.57 (d, J = 8.0 Hz, 2H),

7.26 (d, J = 8.0 Hz, 2H), 6.38 (s, 1H), 4.35 – 4.02 (m, 2H), 3.53 (q, J

= 17.0, 9.3 Hz, 2H), 2.99 (q, J = 9.3, 3.7 Hz, 2H), 2.92 (d, J = 9.2 Hz,

2H), 2.47 (q, J = 17.9, 7.2 Hz, 2H), 2.36 (s, 3H), 1.76 – 1.64 (m, 1H),

1.64 – 1.54 (m, 1H), 1.29 (t, J = 7.1 Hz, 4H), 1.18 (t, J = 5.1 Hz, 1H),

1.06 – 1.01 (m, 1H), 0.98 (t, J = 7.2 Hz, 3H); ¹³C NMR (101 MHz,

(400 MHz, CDCl₃) δ 7.72 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz,

2H), 7.31 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.65 (s, 1H),

4.03 (m, 2H), 3.41 (s, 1H), 3.25 (d, J = 9.3 Hz, 1H), 2.82 (q, J = 9.3,

3.8 Hz, 1H), 2.54 (d, J = 9.3 Hz, 1H), 2.33 (s, 3H), 1.71 – 1.62 (m,

1H), 1.18 (t, J = 5.4 Hz, 1H), 1.02 (m, 4H); ¹³C NMR (101 MHz,

CDCl₃) δ 193.1, 164.2, 148.0, 143.7, 140.3, 135.4, 131.9, 131.6,

130.5, 129.6, 129.2, 127.4, 61.5, 50.9, 48.8, 29.18, 28.0, 21.5, 18.0,

13.9; HR-MS (ESI) calcd for [M + H]⁺: C₂₄H₂₅ClNO₅S: 474.1136,

found: 474.1121; IR (KBr): 3061, 2995, 1770, 1636, 1587, 1460,

1165, 817 cm^-1.

CDCl₃) δ 196.4, 167.5, 144.7, 143.9, 135.1, 132.9, 129.8, 127.5, 618, Ethyl

50.21, 48.9, 32.1, 28.9, 27.7, 21.6, 17.6, 14.1, 7.85; HR-MS (ESI) azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1e). The title compound

calcd for [M + H]⁺: C₂₀H₂₆NO₅S: 392.1526, found: 392.1514; IR was

prepared from ethyl 3-(4-chlorophenyl)-2-diazo-3-

(KBr): 3026, 2982, 1725, 1698, 1633, 1456, 1165, 816, cm^-1.

Ethyl (Z)-2-benzoyl-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-

(Z)-2-(4-chlorobenzoyl)-3-(3-tosyl-3-

oxopropanoate (1e) (111.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and

purified by column chromatography to give yellow oil liquid (131.7

yl)acrylate (3-1c). The title compound was prepared from ethyl 2-

diazo-3-oxo-3-phenylpropanoate (1c) (87.0 mg, 0.4 mmol) and N-

allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg,

0.4 mmol), and purified by column chromatography to give white

1

mg, 70%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33; H NMR

(400 MHz, CDCl₃) δ 7.72 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz,

2H), 7.32 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 6.65 (s, 1H),

4.03 (m, 2H), 3.43 (d, J = 9.3 Hz, 1H), 3.25 (d, J = 9.3 Hz, 1H), 2.82

This journal is © The Royal Society of Chemistry 20xx

J. Name., 2019, 00, 1-3 | 5

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Organic & Biomolecular Chemistry

Page 6 of 14

ARTICLE

Journal Name

(q, J = 9.3, 3.8 Hz, 1H), 2.55 (d, J = 9.3 Hz, 1H), 2.34 (s, 3H), 1.71 – C₂₅H₂₇NO₅S: 454.1683, found: 454.1658; IR (KBr)_V:_ie3_w0_A1_rt8_ic,_le2_O9_n2_lin3_e,

1.63 (m, 1H), 1.18 (t, J = 5.3 Hz, 1H), 1.03 (m, 4H); ¹³C NMR (101 1722, 1696, 1635, 1399, 1166, 1050, 817 cm^DO. ^{I: 10.1039/C9OB01028A}

-1

MHz, CDCl₃) δ 193.1, 164.2, 148.0, 143.7, 140.4, 135.4, 131.8,

Ethyl

(Z)-2-(4-methylbenzoyl)-3-(3-tosyl-3-

131.6, 130.5, 129.6, 129.2, 127.4, 61.5, 50.8, 48.8, 29.18, 28.0, 21.5,

18.0, 13.9; HR-MS (ESI) calcd for [M + H]⁺: C₂₄H₂₅ClNO₅S:

474.1136, found: 474.1121; IR (KBr): 3061, 2995, 1770, 1636, 1587,

1460, 1165, 817 cm^-1.

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1g). The title compound

was prepared from ethyl 2-diazo-3-oxo-3-(p-tolyl)propanoate (1g)

(93.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1-

yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by

Ethyl

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1f). The title compound R_f(petroleum ether/ethyl acetate = 4:1) 0.33; H NMR (400 MHz,

was prepared from ethyl 3-(4-bromophenyl)-2-diazo-3- CDCl3) δ 7.76 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 10.21 –

(E)-2-(4-bromobenzoyl)-3-(3-tosyl-3- column chromatography to give yellow oil liquid (150.4 mg, 83%).

1

oxopropanoate (1f) (130.2 mg, 0.4 mmol) and N-allyl-4-methyl-N- 5.69 (m, 5H), 7.38 – 7.25 (m, 2H), 7.17 (d, J = 8.1 Hz, 2H), 6.73 (s,

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and 1H), 4.11 (m, 2H), 3.48 (d, J = 9.3 Hz, 1H), 3.32 (d, J = 9.3 Hz, 1H),

purified by column chromatography to give yellow oil liquid (19.3 2.89 (q, J = 9.3, 3.8 Hz, 1H), 2.75 (d, J = 9.3 Hz, 1H), 2.49 (s, 3H),

mg, 9%). R_f(petroleum ether/ethyl acetate = 4:1) 0.34; ¹H NMR 2.41 (s, 3H), 1.78 – 1.63 (m, 1H), 1.26 (t, J = 7.1 Hz, 1H), 1.19 (q, J

(400 MHz, CDCl₃) δ 7.64 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.3 Hz, = 6.5, 3.9 Hz, 1H), 1.09 (t, J = 7.1 Hz, 4H); ¹³C NMR (101 MHz,

2H), 7.30 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 7.9 Hz, 2H), 6.65 (s, 1H), CDCl₃) δ 194.0, 164.6, 146.8, 144.9, 143.5, 134.5, 132.4, 132.1,

4.13 – 3.91 (m, 2H), 3.43 (d, J = 9.3 Hz, 1H), 3.25 (d, J = 9.2 Hz, 129.6, 129.3, 127.5, 61.3, 50.9, 48.9, 29.0, 27.7, 21.9, 21.5, 17.7,

1H), 2.82 (q, J = 9.3, 3.7 Hz, 1H), 2.54 (d, J = 9.2 Hz, 1H), 2.34 (s, 14.0; HR-MS (ESI) calcd for [M + H]⁺: C₂₅H₂₇NO₅S: 454.1683,

3H), 1.70 – 1.59 (m, 1H), 1.19 (t, J = 5.1 Hz, 1H), 1.08 – 0.98 (m, found: 454.1658; IR (KBr): 3018, 2923, 1722, 1696, 1635, 1399,

4H); ¹³C NMR (101 MHz, CDCl₃) δ 193.3, 164.2, 148.1, 143.8, 1166, 1050, 817 cm^-1.

135.8, 132.2, 131.8, 131.6, 130.6, 130.5, 129.6, 129.2, 127.4, 61.5,

Ethyl

(Z)-2-(3-methylbenzoyl)-3-(3-tosyl-3-

50.9, 48.8, 29.2, 28.0, 21.6, 18.0, 14.0; HR-MS (ESI) calcd for [M +

H]⁺: C₂₄H₂₅BrNO₅S: 518.0631, found: 518.0597; IR (KBr): 3009,

2926, 1719, 1698, 1635, 1399, 1165, 818 cm^-1.

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1h). The title compound

was prepared from ethyl 2-diazo-3-oxo-3-(m-tolyl)propanoate (1h)

(93.0 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1-

Ethyl

(Z)-2-(4-bromobenzoyl)-3-(3-tosyl-3- yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1f). The title compound column chromatography to give yellow oil liquid (132.4 mg, 73%).

1

was

prepared

from

ethyl

3-(4-bromophenyl)-2-diazo-3- R_f(petroleum ether/ethyl acetate = 4:1) 0.33; H NMR (400 MHz,

oxopropanoate (1f) (130.2 mg, 0.4 mmol) and N-allyl-4-methyl-N- CDCl₃) δ 7.72 – 7.57 (m, 2H), 7.48 – 7.34 (m, 4H), 7.18 (d, J = 8.1

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and Hz, 2H), 6.75 (s, 1H), 4.28 – 3.94 (m, 2H), 3.53 (t, J = 22.4 Hz, 1H),

purified by column chromatography to give yellow oil liquid (163.2 3.33 (d, J = 9.3 Hz, 1H), 2.92 (q, J = 9.3, 3.8 Hz, 1H), 2.74 (t, J =

1

mg, 79%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33; H NMR 10.1 Hz, 1H), 2.44 (s, 3H), 2.41 (s, 3H), 1.77 – 1.71 (m, 1H), 1.20 (q,

(400 MHz, CDCl₃) δ 7.64 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.3 Hz, J = 5.4 Hz, 1H), 1.13 – 1.04 (m, 4H); ¹³C NMR (101 MHz, CDCl₃) δ

2H), 7.30 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 7.9 Hz, 2H), 6.65 (s, 1H), 194.5, 164.6, 147.0, 143.5, 138.7, 136.9, 134.7, 132.4, 132.1, 129.6,

4.13 – 3.91 (m, 2H), 3.43 (d, J = 9.3 Hz, 1H), 3.25 (d, J = 9.2 Hz, 129.4, 128.7, 127.5, 126.6, 61.4, 50.9, 48.9, 29.1, 27.8, 21.5, 21.4,

1H), 2.82 (q, J = 9.3, 3.7 Hz, 1H), 2.54 (d, J = 9.2 Hz, 1H), 2.34 (s, 17.7, 13.9; HR-MS (ESI) calcd for [M + H]⁺: C₂₅H₂₇NO₅S: 454.1683,

3H), 1.70 – 1.59 (m, 1H), 1.19 (t, J = 5.1 Hz, 1H), 1.08 – 0.98 (m, found: 454.1672; IR (KBr): 3018, 2923, 1722, 1696, 1635, 1399,

4H); ¹³C NMR (101 MHz, CDCl₃) δ 193.3, 164.2, 148.05, 143.8, 1166, 1050, 817 cm^-1.

135.8, 132.2, 131.8, 131.6, 130.6, 130.5, 129.6, 129.2, 127.4, 61.5,

Ethyl

(E)-2-(2-methylbenzoyl)-3-(3-tosyl-3-

50.9, 48.8, 29.2, 28.0, 21.6, 18.0, 14.0; HR-MS (ESI) calcd for [M +

H]⁺: C₂₄H₂₅BrNO₅S: 518.0631, found: 518.0597; IR (KBr): 3009,

2926, 1719, 1698, 1635, 1399, 1165, 818 cm^-1.

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1i). The title compound

was prepared from ethyl 2-diazo-3-oxo-3-(o-tolyl)propanoate (1i)

(93.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1-

Ethyl

(E)-2-(4-methylbenzoyl)-3-(3-tosyl-3- yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1g). The title compound column chromatography to give white solid (20.1 mg, 11%). R_f

was prepared from ethyl 2-diazo-3-oxo-3-(p-tolyl)propanoate (1g) (petroleum ether/ethyl acetate = 4:1) 0.34; m.p. 109.0-110 ^oC; ¹H

(93.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1- NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2

yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by Hz, 3H), 7.13 (m, J = 21.0, 11.1, 7.0 Hz, 3H), 6.11 (s, 1H), 4.11 (q, J

column chromatography to give yellow oil liquid (15.4 mg, 8%). R_f= 7.1 Hz, 2H), 3.61 (d, J = 9.4 Hz, 1H), 3.51 (d, J = 9.4 Hz, 1H),

(petroleum ether/ethyl acetate = 4:1) 0.34; ¹H NMR (400 MHz, 3.03 (q, J = 9.4, 3.8 Hz, 1H), 2.97 (d, J = 9.4 Hz, 1H), 2.36 (s, 3H),

CDCl₃) δ 7.68 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.21 (d, 2.25 (s, 3H), 1.69 – 1.61 (m, 1H), 1.24 – 1.16 (m, 1H), 1.13 (t, J =

J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.65 (s, 1H), 4.03 (m, 2H), 7.1 Hz, 3H), 1.01 (q, J = 8.0, 5.6 Hz, 1H); ¹³C NMR (101 MHz,

3.40 (d, J = 9.3 Hz, 1H), 3.23 (d, J = 9.3 Hz, 1H), 2.81 (q, J = 9.3, CDCl₃) δ 194.5, 166.5, 149.0, 143.9, 137.5, 136.8, 136.6, 133.2,

3.8 Hz, 1H), 2.68 (d, J = 9.3 Hz, 1H), 2.41 (s, 3H), 2.33 (s, 3H), 1.67 131.2, 130.6, 129.8, 127.6, 127.5, 125.3, 61.7, 50.3, 48.8, 29.3, 28.2,

– 1.60 (m, 1H), 1.17 (t, 1H), 1.10 (t, J = 5.2 Hz, 1H), 1.00 (t, J = 7.1 21.6, 19.7, 18.0, 13.9; HR-MS (ESI) calcd for [M + H]⁺:

Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 194.0, 164.6, 146.8, 144.9, C₂₅H₂₇NO₅S: 454.1683, found: 454.1670; IR (KBr): 3018, 2923,

143.5, 134.5, 132.4, 132.1, 129.6, 129.3, 127.5, 61.3, 50.9, 48.9, 1722, 1696, 1635, 1399, 1166, 1050, 817 cm^-1.

29.0, 27.7, 21.9, 21.5, 17.7, 14.0.HR-MS (ESI) calcd for [M + H]⁺:

6 | J. Name., 2019, 00, 1-3

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Page 7 of 14

Organic & Biomolecular Chemistry

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Journal Name

Ethyl

ARTICLE

(Z)-2-(2-methylbenzoyl)-3-(3-tosyl-3- (prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0_V.4_iewm_Am_rtico_ll_e)_O, _na_ln_ind_e

DOI: 10.1039/C9OB01028A

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1i). The title compound purified by column chromatography to give yellow oil liquid (19.3

was prepared from ethyl 2-diazo-3-oxo-3-(o-tolyl)propanoate (1i) mg, 10%). R_f(petroleum ether/ethyl acetate = 4:1) 0.34; ¹H NMR

(93.0 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1- (400 MHz, CDCl₃) δ 7.66 (d, J = 8.0 Hz, 2H), 7.42 (t, J = 7.2 Hz,

yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.97 (t, J = 7.5 Hz, 1H), 6.88 (d, J =

column chromatography to give white solid (107.3 mg, 59%). R_f8.7 Hz, 1H), 6.36 (s, 1H), 4.10 (q, J = 13.0, 6.2 Hz, 2H), 3.80 – 3.69

(petroleum ether/ethyl acetate = 4:1) 0.33; m.p. 109.0-110 ^oC; ¹H (m, 4H), 3.58 (d, J = 9.3 Hz, 1H), 3.13 (q, J = 9.3, 3.8 Hz, 1H), 3.03

NMR (400 MHz, CDCl₃) δ 7.53 – 7.42 (m, 4H), 7.35 (d, J = 7.5 Hz, (d, J = 9.4 Hz, 1H), 2.43 (s, 3H), 1.72 (m, 1H), 1.26 (s, 2H), 1.13 (t,

1H), 7.20 (t, J = 6.7 Hz, 3H), 6.69 (s, 1H), 4.08 (m, 2H), 3.53 (d, J = J = 7.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 191.6, 165.8, 157.4,

9.4 Hz, 1H), 3.38 (d, J = 9.4 Hz, 1H), 2.97 (q, J = 9.3, 3.8 Hz, 1H), 148.3, 143.8, 136.9, 133.2, 132.8, 129.9, 129.7, 127.8, 127.6, 120.6,

2.84 (d, J = 9.4 Hz, 1H), 2.67 (s, 3H), 2.42 (s, 3H), 1.82 – 1.68 (m, 111.1, 61.1, 55.4, 50.9, 49.0, 29.7, 29.2, 28.2, 21.5, 17.8, 13.9; HR-

1H), 1.22 (t, J = 5.3 Hz, 1H), 1.12 (q, J = 7.9, 5.6 Hz, 1H), 1.11 – MS (ESI) calcd for [M + H]⁺: C₂₅H₂₈NO₆S: 470.1632, found:

1.01 (m, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 196.0, 164.7, 146.5, 470.1627; IR (KBr): 3050, 2980, 1716, 1660, 1598, 1510, 1206,

143.6, 140.1, 136.2, 134.0, 132.5, 132.4, 132.3, 131.4, 129.6, 127.5, 1166, 815 cm-¹.

125.7, 61.3, 50.9, 48.9, 29.1, 27.8, 21.7, 21.5, 17.7, 13.8; HR-MS

Ethyl

(Z)-2-(2-methoxybenzoyl)-3-(3-tosyl-3-

(ESI) calcd for [M + H]⁺: C₂₅H₂₇NO₅S: 454.1683, found: 454.1670;

IR (KBr): 3018, 2923, 1722, 1696, 1635, 1399, 1166, 1050, 817 cm^-1.

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1k). The title compound

was prepared from ethyl 2-diazo-3-(2-methoxyphenyl)-3-

Ethyl

(E)-2-(4-methoxybenzoyl)-3-(3-tosyl-3- oxopropanoate (1k) (99.0 mg, 0.4 mmol) and N-allyl-4-methyl-N-

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1j). The title compound (prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and

was prepared from ethyl 2-diazo-3-(4-methoxyphenyl)-3- purified by column chromatography to give yellow oil liquid (71.2

oxopropanoate (1j) (99.2 mg, 0.4 mmol) and N-allyl-4-methyl-N- mg, 38%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33; ¹H NMR

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and (400 MHz, CDCl₃) δ 7.93 (d, J = 7.7 Hz, 1H), 7.57 (t, J = 7.7 Hz,

purified by column chromatography to give yellow oil liquid (7.5 mg, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 6.48 (s, 1H),

1

4%). R_f(petroleum ether/ethyl acetate = 4:1) 0.34; H NMR (400 4.08 (q, J = 12.6, 7.0 Hz, 2H), 3.70 (s, 3H), 3.49 (d, J = 9.3 Hz, 1H),

MHz, CDCl₃) δ 7.76 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 3.42 (d, J = 9.3 Hz, 1H), 2.40 (s, 3H), 1.68 – 1.61 (m, 1H), 1.10 (t, J

7.10 (d, J = 10.9 Hz, 2H), 6.88 (d, J = 7.6 Hz, 2H), 6.63 (s, 1H), 4.09 = 5.1 Hz, 1H), 1.05 (t, J = 7.1 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃)

– 4.00 (m, 2H), 3.86 (s, 3H), 3.41 (d, J = 9.3 Hz, 1H), 3.24 (d, J = δ 192.1, 164.8, 159.4, 143.4, 143.1, 136.9, 135.1, 132.5, 131.1,

9.3 Hz, 1H), 2.82 (q, J = 9.3, 3.8 Hz, 1H), 2.70 (d, J = 9.3 Hz, 1H), 129.6, 127.5, 126.7, 121.0, 111.9, 60.9, 55.4, 51.7, 49.1, 28.7, 27.4,

2.33 (s, 3H), 1.66 – 1.61 (m, 1H), 1.16 (t, J = 7.0 Hz, 1H), 1.11 (t, J 21.5, 17.4, 13.9; HR-MS (ESI) calcd for [M + H]⁺: C₂₅H₂₈NO₆S:

= 4.2 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) 470.1632, found: 470.1627; IR (KBr): 3058, 2980, 1721, 1651, 1597,

δ 192.8, 164.6, 164.2, 146.5, 143.6, 132.4, 132.1, 131.6, 130.1, 1484, 1214, 1166, 816 cm^-1.

129.6, 127.5, 114.1, 61.3, 55.6, 50.8, 48.9, 29.0, 27.7, 21.5, 17.7,

Ethyl

(trifluoromethyl)benzoyl)acrylate (3-1l). The title compound was

prepared from ethyl 2-diazo-3-oxo-3-(4-

(trifluoromethyl)phenyl)propanoate (1l) (114.3 mg, 0.4 mmol) and

(Z)-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-yl)-2-(4-

14.0; HR-MS (ESI) calcd for [M + H]⁺: C₂₅H₂₈NO₆S: 470.1632,

found: 470.1611; 3050, 2980, 1716, 1660, 1598, 1510, 1206, 1166,

815 cm^-1.

Ethyl

(Z)-2-(4-methoxybenzoyl)-3-(3-tosyl-3- N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1j). The title compound mg, 0.4 mmol), and purified by column chromatography to give

was prepared from ethyl 2-diazo-3-(4-methoxyphenyl)-3- yellow oil liquid (97.0 mg, 48%). R_f(petroleum ether/ethyl acetate =

1

oxopropanoate (1j) (99 mg, 0.4 mmol) and N-allyl-4-methyl-N- 4:1) 0.30; H NMR (400 MHz, CDCl₃) δ 7.98 (d, J = 8.0 Hz, 2H),

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and 7.78 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 7.8 Hz, 2H), 7.11 (d, J = 7.8 Hz,

purified by column chromatography to give yellow oil liquid (116 2H), 6.78 (s, 1H), 4.11 (q, J = 12.7, 5.9 Hz, 2H), 3.52 (d, J = 9.3 Hz,

mg, 62%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33; ¹H NMR 1H), 3.36 (d, J = 9.2 Hz, 1H), 2.92 (q, J = 9.2, 3.3 Hz, 1H), 2.62 (d, J

(400 MHz, CDCl₃) δ 7.55 – 7.43 (m, 4H), 7.35 (d, J = 7.5 Hz, 1H), = 9.2 Hz, 1H), 2.38 (s, 3H), 1.87 – 1.70 (m, 1H), 1.30 (t, J = 5.1 Hz,

7.20 (t, J = 6.7 Hz, 3H), 6.69 (s, 1H), 4.13 – 4.03 (m, 2H), 3.53 (d, J 1H), 1.18 – 1.12 (m, 1H), 1.07 (t, J = 7.1 Hz, 3H); ¹³C NMR (101

= 9.4 Hz, 1H), 3.38 (d, J = 9.4 Hz, 1H), 2.97 (q, J = 9.3, 3.8 Hz, 1H), MHz, CDCl3) δ 193.24, 164.10, 148.80, 143.79, 139.55, 135.08,

2.84 (d, J = 9.4 Hz, 1H), 2.67 (s, 3H), 2.42 (s, 3H), 1.81 – 1.70 (m, 131.96, 131.40, 129.5, 129.4, 127.4, 125.9 (q, J = 10 Hz, ²J_CF), 61.6,

1H), 1.22 (t, J = 5.3 Hz, 1H), 1.14 – 1.09 (m, 1H), 1.06 (t, J = 7.1 Hz, 51.0, 48.8, 29.3, 28.2, 21.5, 18.1, 13.9; HR-MS (ESI) calcd for [M +

3H); ¹³C NMR (101 MHz, CDCl₃) δ 192.8, 164.6, 164.2, 146.5, H]⁺: C₂₅H₂₅F₃NO₅S: 508.1400, found: 508.1385; IR (KBr): 3058,

143.6, 132.4, 132.1, 131.6, 130.1, 129.6, 127.5, 114.1, 61.3, 55.6, 2980, 1721, 1651, 1597, 1484, 1214, 1166, 816 cm^-1.

50.8, 48.9, 29.0, 27.7, 21.5, 17.7, 14.0; HR-MS (ESI) calcd for [M +

Ethyl (Z)-2-(2-naphthoyl)-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)acrylate (3-1m). The title compound was prepared from ethyl 2-

diazo-3-(naphthalen-2-yl)-3-oxopropanoate (1m) (107.2 mg, 0.4

H]⁺: C₂₅H₂₈NO₆S: 470.1632, found: 470.1611; IR (KBr): 3050, 2980,

1716, 1660, 1598, 1510, 1206, 1166, 815 cm^-1.

Ethyl

(E)-2-(2-methoxybenzoyl)-3-(3-tosyl-3- mmol) and N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1k). The title compound (2a) (99.6 mg, 0.4 mmol), and purified by column chromatography

was prepared from ethyl 2-diazo-3-(2-methoxyphenyl)-3- to give yellow oil liquid (117.4 mg, 60%). R_f(petroleum ether/ethyl

oxopropanoate (1k) (99.0 mg, 0.4 mmol) and N-allyl-4-methyl-N- acetate = 4:1) 0.33; ¹H NMR (400 MHz, CDCl₃) δ 8.18 (s, 1H), 7.96

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Journal Name

(dd, J = 8.6, 1.4 Hz, 1H), 7.93 – 7.87 (m, 2H), 7.84 (d, J = 8.2 Hz, 7.40 (d, J = 7.9 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.23_V(_ied_w, _AJ_rt=_icl7_e._O9_nH_linez,

DOI: 10.1039/C9OB01028A

1H), 7.62 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.11 (d, J = 2H), 6.83 (s, 1H), 3.48 (d, J = 9.4 Hz, 1H), 3.04 (d, J = 9.2 Hz, 1H),

8.1 Hz, 2H), 6.69 (s, 1H), 6.59 (d, J = 7.9 Hz, 2H), 4.02 (m, 2H), 2.87 (q, J = 9.4, 3.5 Hz, 1H), 2.71 (d, J = 9.2 Hz, 1H), 2.43 (s, 6H),

3.39 (d, J = 9.3 Hz, 1H), 3.29 (d, J = 9.3 Hz, 1H), 2.76 (q, J = 9.3, 1.80 – 1.73 (m, 1H), 1.29 (d, J = 5.9 Hz, 1H), 1.16 – 1.06 (m, 1H);

3.8 Hz, 1H), 2.57 (d, J = 9.3 Hz, 1H), 2.02 (s, 3H), 1.73 – 1.63 (m, ¹³C NMR (101 MHz, CDCl₃) δ 191.2, 145.0, 144.6, 143.7, 140.8,

1H), 1.19 – 1.16 (m, 1H), 1.07 (q, J = 7.8, 5.6 Hz, 1H), 0.97 (t, J = 136.6, 136.3, 134.7, 132.4, 130.0, 129.8, 129.8, 129.0, 128.6, 127.4,

7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 194.2, 164.6, 147.8, 50.2, 48.6, 28.7, 28.0, 21.7, 21.5, 17.7; HR-MS (ESI) calcd for [M +

143.4, 136.0, 134.5, 132.6, 132.2, 131.8, 131.4, 129.8, 129.3, 129.1, H]⁺: C₂₈H₂₇NO₅S₂: 522.1403, found: 522.1402; IR (KBr): 3066,

128.9, 128.0, 127.3, 127.1, 124.0, 61.4, 51.0, 48.9, 29.4, 28.0, 21.2, 2983, 1595, 1494, 1166, 818 cm^-1.

18.0, 14.0; HR-MS (ESI) calcd for [M + H]⁺: C₂₈H₂₈NO₅S: 490.1683,

found: 490.1670; IR (KBr): 3061, 2986, 1719, 1664, 1600, 1466,

1167, 817 cm^-1.

(Z)-1-Phenyl-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)butane-1,3-dione (3-1q). The title compound was

prepared from 2-diazo-1-phenylbutane-1,3-dione (1q) (75.1 mg, 0.4

Ethyl

(Z)-2-(thiophene-2-carbonyl)-3-(3-tosyl-3- mmol) and N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

azabicyclo[3.1.0]hexan-1-yl)acrylate (3-1n). The title compound (2a) (99.6 mg, 0.4 mmol), and purified by column chromatography

was prepared from ethyl 2-diazo-3-oxo-3-(thiophen-2-yl)propanoate to give yellow oil (62.3 mg, 38%). R_f(petroleum ether/ethyl acetate

(1n) (90.2 mg, 0.4 mmol) and N-allyl-4-methyl-N-(prop-2-yn-1- = 4:1) 0.33; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J = 7.6 Hz, 2H),

yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by 7.66 (t, J = 7.3 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.41 (d, J = 8.1 Hz,

column chromatography to give yellow oil liquid (100.2 mg, 56%). 2H), 7.19 (d, J = 7.9 Hz, 2H), 6.60 (s, 1H), 3.48 (d, J = 9.3 Hz, 1H),

1

R_f(petroleum ether/ethyl acetate = 4:1) 0.33; H NMR (400 MHz, 3.25 (d, J = 9.3 Hz, 1H), 2.88 (q, J = 9.3, 3.6 Hz, 1H), 2.73 (d, J =

CDCl₃) δ 7.71 (d, J = 4.8 Hz, 1H), 7.46 (d, J = 3.7 Hz, 1H), 7.43 (d, 9.3 Hz, 1H), 2.41 (s, 3H), 2.19 (s, 3H), 1.76 – 1.70 (m, 1H), 1.19 (t,

J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.09 – 7.04 (m, 1H), 6.64 J = 5.2 Hz, 1H), 1.12 – 1.06 (m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ

(s, 1H), 4.07 (m, 2H), 3.43 (d, J = 9.3 Hz, 1H), 3.26 (d, J = 9.3 Hz, 196.8, 195.0, 145.8, 143.7, 140.8, 136.8, 134.2, 132.1, 129.7, 129.2,

1H), 2.87 – 2.73 (m, 2H), 2.34 (s, 3H), 1.72 – 1.61 (m, 1H), 1.15 (t, 129.1, 127.4, 50.8, 48.8, 29.0, 28.1, 27.0, 21.5, 17.9; HR-MS (ESI)

J = 5.3 Hz, 1H), 1.06 (q, J = 7.4 Hz, 4H); ¹³C NMR (101 MHz, calcd for [M + H]⁺: C₂₃H₂₃NO₄S: 410.1421, found: 410.1411; IR

CDCl₃) δ 186.4, 164.3, 147.2, 144.5, 143.7, 135.5, 134.4, 132.1, (KBr): 3067, 2925, 1655, 1623, 1597, 1449, 1166, 816 cm^-1.

131.8, 129.7, 128.5, 127.5, 61.5, 50.5, 48.8, 29.1, 28.0, 21.6, 17.9,

1,3-Diphenyl-2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)propane-1,3-dione (3-1r). The title compound was

prepared from 2-diazo-1,3-diphenylpropane-1,3-dione (1r) (99.6 mg,

14.0; HR-MS (ESI) calcd for [M + H]⁺: C₂₈H₂₈NO₅S: 446.1090,

found: 446.1098; IR (KBr): 3058, 2986, 1717, 1640, 1595, 1515,

1166, 815 cm^-1.

0.4

mmol)

and

N-allyl-4-methyl-N-(prop-2-yn-1-

Diethyl (Z)-(3-oxo-3-phenyl-1-(3-tosyl-3-azabicyclo[3.1.0]

hexan-1-yl)prop-1-en-2-yl)phosphonate (3-1o). The

yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and purified by

column chromatography to give white solid (51.0 mg, 27%). R_f

title

0

(petroleum ether/ethyl acetate = 4:1) 0.33; m.p. 167.0-168.0 C ¹H

compound was prepared from diethyl (1-diazo-2-oxo-2-

phenylethyl)phosphonate (1o) (113.2 mg, 0.4 mmol) and N-allyl-4-

methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4

mmol), and purified by column chromatography to give yellow oil

liquid (46.3 mg, 23%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33;

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, 2H), 7.57 (t, J = 7.4 Hz, 1H),

7.41 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.0 Hz,

2H), 6.50 (d, J = 25.3 Hz, 1H), 3.96 (m, 4H), 3.38 (d, J = 9.4 Hz,

1H), 3.06 (d, J = 9.3 Hz, 1H), 2.79 (q, J = 9.3, 3.8 Hz, 1H), 2.70 (d, J

= 9.3 Hz, 1H), 2.36 (s, 3H), 1.64 – 1.55 (m, 1H), 1.18 (s, 1H), 1.12

(m, J = 7.1, 1.5 Hz, 6H), 0.97 (d, J = 3.6 Hz, 1H); ¹³C NMR (101

NMR (400 MHz, CDCl₃) δ 7.85 (d, J = 7.7 Hz, 2H), 7.69 (d, J = 7.6

Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.52 – 7.36 (m, 8H), 7.16 (d, J =

8.0 Hz, 2H), 6.38 (s, 1H), 3.50 (d, J = 9.4 Hz, 1H), 3.40 (d, J = 9.4

Hz, 1H), 2.96 (q, J = 9.4, 3.7 Hz, 1H), 2.78 (d, J = 9.4 Hz, 1H), 2.39

(s, 3H), 1.76 – 1.65 (m, 1H), 1.19 (t, J = 5.3 Hz, 1H), 1.09 – 1.02 (m,

1H); ¹³C NMR (101 MHz, CDCl₃) δ 195.4, 193.6, 148.6, 143.6,

140.9, 137.2, 137.0, 133.9, 132.6, 132.4, 129.6, 129.3, 129.3, 128.9,

128.2, 127.5, 51.3, 48.9, 29.4, 28.2, 21.5, 18.0; HR-MS (ESI) calcd

for [M + H]⁺: C₂₈H₂₆NO₄S: 473.1577, found: 473.1571; IR (KBr):

3072, 2919, 1632, 1491, 1165 cm^-1.

MHz, CDCl₃) δ 194.6, 194.5, 149.9, 143.6, 136.6, 134.1, 132.3, Dimethyl

2-((3-tosyl-3-azabicyclo[3.1.0]hexan-1-

129.7, 129.7, 128.7, 127.4, 62.7, 58.4, 50.7, 48.7, 30.1, 29.8, 27.3, yl)methylene)malonate (3-1s). The title compound was prepared

21.5, 18.4, 17.2, 16.1, 16.0; HR-MS (ESI) calcd for [M + H]⁺: from dimethyl 2-diazomalonate (1s) (63.2 mg, 0.4 mmol) and N-

C₂₅H₃₀NO₆PS: 504.1554, found: 504.1602; IR (KBr): 3066, 2986, allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg,

1658, 1632, 1595, 1500, 1166, 818 cm^-1.

0.4 mmol), and purified by column chromatography to give yellow

oil (66.9 mg, 44%). R_f(petroleum ether/ethyl acetate = 4:1) 0.33; ¹H

NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.0

Hz, 2H), 6.54 (s, 1H), 3.75 (s, 3H), 3.67 (s, 3H), 3.51 (t, J = 9.8 Hz,

2H), 2.97 (q, J = 9.3, 3.8 Hz, 1H), 2.91 (d, J = 9.1 Hz, 1H), 2.37 (s,

3H), 1.68 (q, J = 8.0, 4.2 Hz, 1H), 1.19 (t, J = 5.2 Hz, 1H), 1.04 (q, J

= 8.0, 5.6 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 166.4, 164.0,

147.3, 144.0, 132.8, 129.8, 127.6, 126.5, 53.4, 52.6, 50.0, 48.8, 28.9,

27.8, 21.6, 17.6; HR-MS (ESI) calcd for [M + H]⁺: C₁₈H₂₂NO₆S:

(Z)-1-Phenyl-2-tosyl-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)prop-2-en-1-one (3-1p). The title compound was prepared from

2-diazo-1-phenyl-2-tosylethan-1-one (1p) (120.2 mg, 0.4 mmol) and

N-allyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6

mg, 0.4 mmol), and purified by column chromatography to give

yellow oil (17.2 mg, 8%). R_f(petroleum ether/ethyl acetate = 4:1)

0.33; ¹H NMR (400 MHz, CDCl₃) δ 7.88 (d, J = 7.8 Hz, 2H), 7.68 (t,

J = 7.4 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H),

8 | J. Name., 2019, 00, 1-3

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ARTICLE

380.1162, found: 380.1151; IR (KBr): 3003, 2954, 2924, 1727, 1638, 7.28 (d, J = 7.8 Hz, 2H), 7.18 (t, J = 7.1 Hz, 2H), 7.16 – 7.09 (m,

View Article Online

DOI: 10.1039/C9OB01028A

1270, 814, cm^-1.

1H), 7.01 (d, J = 7.5 Hz, 2H), 6.11 (s, 1H), 4.23 – 4.02 (m, 2H), 3.76

– 3.66 (m, 2H), 3.15 (q, J = 9.3, 3.6 Hz, 1H), 3.06 (d, J = 9.3 Hz,

1H), 2.65 (d, J = 4.8 Hz, 1H), 2.36 (s, 3H), 2.22 (t, J = 4.0 Hz, 1H),

1.91 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ

194.0, 166.7, 144.0, 143.2, 138.4, 135.1, 133.1, 129.9, 128.6, 128.4,

127.6, 127.1, 61.7, 51.5, 49.5, 35.1, 33.4, 32.0, 26.2, 21.6 14.1; HR-

MS (ESI) calcd for [M + H]⁺: C₂₅H₂₈NO₄S: 454.1642, found:

454.1678; IR (KBr): 3036, 2928, 1722, 1630, 1553, 1496, 1164, 819

cm^-1.

Ethyl

(Z)-2-phenyl-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)acrylate (3-1t). The title compound was prepared from ethyl 2-

diazo-2-phenylacetate (1t) (76.4 mg, 0.4 mmol) and N-allyl-4-

methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4

mmol), and purified by column chromatography to give yellow oil

(25.2 mg, 15%). R_f(petroleum ether/ethyl acetate = 5:1) 0.33; H

NMR (400 MHz, CDCl₃) δ 7.72 (d, J = 8.1 Hz, 2H), 7.41 – 7.02 (m,

7H), 5.98 (s, 1H), 4.38 – 4.10 (m, 2H), 3.72 (d, J = 9.2 Hz, 1H), 3.60

1

(d, J = 9.3 Hz, 1H), 3.18 (q, J = 9.2, 3.7 Hz, 1H), 3.10 (d, J = 9.2 Hz, Ethyl

(Z)-2-((6-methyl-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

1H), 2.46 (s, 3H), 1.66 – 1.52 (m, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.01 yl)methylene)-3-oxobutanoate (3-2b). The title compound was

– 0.88 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 168.6, 143.6, 138.1, prepared from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4

136.4, 133.5, 132.1, 129.7, 128.5, 128.2, 127.6, 126.3, 61.3, 52.2, mmol)

and

N-(but-2-en-1-yl)-4-methyl-N-(prop-2-yn-1-

49.7, 28.3, 25.0, 21.5, 15.5, 14.2; HR-MS (ESI) calcd for [M + H]⁺: yl)benzenesulfonamide (2c) (105.0 mg, 0.4 mmol), and purified by

C₂₃H₂₅NO₄S: 412.1577, found: 412.1555; IR (KBr): 3003, 2926, column chromatography to give yellow oil (25.2 mg, 16%). R_f

1

1729, 1552, 1494, 1165, 818 cm^-1.

(petroleum ether/ethyl acetate = 5:1) 0.33; H NMR (400 MHz,

CDCl₃) δ 7.64 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.65 (s,

1H), 4.37 – 4.12 (m, 2H), 3.60 (q, J = 9.1, 4.1 Hz, 2H), 3.04 (q, J =

9.2, 2.8 Hz, 1H), 2.98 (d, J = 9.1 Hz, 1H), 2.43 (s, 4H), 2.25 (s, 3H),

Ethyl

(Z)-2-(p-tolyl)-3-(3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)acrylate (3-1u)

The title compound was prepared from ethyl 2-diazo-2-(p-

tolyl)acetate (1u) (81.6 mg, 0.4 mmol) and N-allyl-4-methyl-N-

(prop-2-yn-1-yl)benzenesulfonamide (2a) (99.6 mg, 0.4 mmol), and

purified by column chromatography to give white oil (9.1 mg, 5%).

1.51 (s, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.13 (d, J = 5.8 Hz, 3H); ¹³

NMR (101 MHz, CDCl₃) δ 193.7, 167.1, 144.0, 143.8, 138.2, 133.1,

C

129.7, 127.6, 61.7, 51.17, 49.3, 34.6, 32.7, 26.8, 24.3, 21.5, 14.6,

R_f(petroleum ether/ethyl acetate = 4:1) 0.45; ¹H NMR (400 MHz, 13.2; HR-MS (ESI) calcd for [M + H]⁺: C₂₀H₂₆NO₄S: 392.1526,

CDCl₃) δ 7.42 (d, J = 7.9 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.15 (d,

J = 7.7 Hz, 2H), 7.01 (d, J = 7.7 Hz, 2H), 6.62 (s, 1H), 4.21 – 4.08

(m, 2H), 3.44 (d, J = 9.2 Hz, 1H), 3.03 (d, J = 9.6 Hz, 1H), 2.88 (dd,

J = 9.2, 3.7 Hz, 1H), 2.47 – 2.40 (m, 7H), 1.55 – 1.49 (m, 1H), 1.20

(t, 3H), 1.05 (t, J = 5.1 Hz, 1H), 0.88 (t, 1H). ¹³C NMR (101 MHz,

CDCl₃) δ 167.3, 143.6, 143.0, 137.7, 133.9, 132.5, 132.2, 129.9,

129.5, 128.6, 127.6, 61.0, 51.5, 49.0, 29.7, 29.4, 28.6, 27.1, 17.2,

14.2; HR-MS (ESI) calcd for [M + H]⁺: C₂₄H₂₈NO₄S: 426.1734,

found: 426.1734; IR (KBr): 3416, 2920, 1701, 1631, 1400, 1166,

750 cm^-1.

found:392.1511; IR (KBr): 3009, 2923, 1727, 1692, 1465, 1400,

1165, 817 cm^-1.

Ethyl

(E)-2-((5-methyl-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)-3-oxobutanoate (3-2c). The title compound was

prepared from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4

mmol)

and

4-methyl-N-(2-methylallyl)-N-(prop-2-yn-1-

yl)benzenesulfonamide (2d) (105.2 mg, 0.4 mmol), and purified by

column chromatography to give yellow oil (42.1 mg, 27%). R_f

1

(petroleum ether/ethyl acetate = 5:1) 0.35; H NMR (400 MHz,

Ethyl (E)-3-oxo-2-((6-phenyl-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)butanoate (3-2a). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

CDCl₃) δ 7.59 (d, J = 7.5 Hz, 2H), 7.27 (d, J = 7.7 Hz, 2H), 6.45 (s,

1H), 4.14 (q, J = 7.1 Hz, 2H), 3.48 (q, J = 18.8, 9.3 Hz, 2H), 2.80 –

2.69 (m, 2H), 2.35 (s, 3H), 2.30 (s, 3H), 1.24 – 1.15 (m, 4H), 1.11 (s,

3H), 0.78 (d, J = 5.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl3) δ

193.6, δ 167.3, 143.9, 143.5, 137.3, 132.9, 129.8, 127.6, 61.8, 54.1,

51.2, 33.6, 31.8, 26.7, 23.5, 21.6, 15.3, 14.1; HR-MS (ESI) calcd for

[M + H]⁺: C₂₀H₂₆NO₄S: 392.1526, found: 392.1517; IR (KBr): 3009,

2927, 1727, 1666, 1599, 1444, 1165, 814 cm^-1.

cinnamyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

(2b)

(130.1 mg, 0.4 mmol), and purified by column chromatography to

give yellow oil (22.4 mg, 12%). R_f(petroleum ether/ethyl acetate =

5:1) 0.34; ¹H NMR (400 MHz, CDCl₃) δ 7.71 (d, J = 7.8 Hz, 2H),

7.37 (d, J = 7.8 Hz, 2H), 7.26 (t, J = 5.1 Hz, 2H), 7.21 – 7.17 (m,

1H), 7.02 (d, J = 7.5 Hz, 2H), 6.44 (s, 1H), 4.11 (dd, J = 11.8, 6.1 Hz,

2H), 3.76 (q, J = 12.7, 9.9 Hz, 2H), 3.28 (q, J = 9.4, 3.6 Hz, 1H),

3.01 (d, J = 9.6 Hz, 1H), 2.56 (d, J = 4.6 Hz, 1H), 2.45 (s, 3H), 2.15

(t, J = 4.0 Hz, 1H), 2.05 (s, 3H), 1.26 (s, 1H), 1.18 (t, J = 7.1 Hz,

3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.5, 163.9, 143.9, 143.2,

138.1, 135.5, 133.1, 129.8, 128.5, 128.33, 127.6, 126.9, 61.3, 53.0,

49.8, 35.2, 33.2, 32.6, 30.5, 21.6, 14.0; HR-MS (ESI) calcd for [M +

H]⁺: C₂₅H₂₈NO₄S: 454.1642, found:454.1678; IR (KBr): 3036, 2928,

1722, 1630, 1553, 1496, 1164, 819 cm^-1.

Ethyl

(Z)-2-((5-methyl-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)-3-oxobutanoate (3-2c). The title compound was

prepared from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4

mmol)

and

4-methyl-N-(2-methylallyl)-N-(prop-2-yn-1-

yl)benzenesulfonamide (2d) (105.2 mg, 0.4 mmol), and purified by

column chromatography to give yellow oil (56 mg, 36%). R_f

1

(petroleum ether/ethyl acetate = 5:1) 0.33; H NMR (400 MHz,

CDCl₃) δ 7.58 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.42 (s,

1H), 4.22 (q, J = 7.2 Hz, 2H), 3.54 (t, J = 9.3 Hz, 2H), 2.94 (d, J =

9.2 Hz, 1H), 2.76 (d, J = 9.3 Hz, 1H), 2.37 (s, 3H), 2.17 (s, 3H), 1.29

(t, J = 7.1 Hz, 3H), 1.19 (t, J = 4.8 Hz, 1H), 1.13 (s, 3H), 0.84 (d, J =

5.4 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 193.5, 167.3, 143.9,

143.5, 137.3, 133.1, 129.8, 127.6, 61.8, 54.1, 51.2, 33.6, 31.8, 26.7,

23.4, 21.5, 15.3, 14.1; HR-MS (ESI) calcd for [M + H]⁺:

Ethyl (Z)-3-oxo-2-((6-phenyl-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

yl)methylene)butanoate (3-2a). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

cinnamyl-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

(2b)

(130.2 mg, 0.4 mmol), and purified by column chromatography to

give yellow oil (69.3 mg, 38%). R_f(petroleum ether/ethyl acetate =

1

5:1) 0.33; H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 7.8 Hz, 2H),

This journal is © The Royal Society of Chemistry 20xx

J. Name., 2019, 00, 1-3 | 9

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Organic & Biomolecular Chemistry

Page 10 of 14

ARTICLE

Journal Name

C₂₀H₂₆NO₄S: 392.1526, found: 392.1517; IR (KBr): 3009, 2927, by column chromatography to give yellow oil (91.2_Vm_iewg,_Ar5_tic8_le%_O)_n._linR_e_f

1

1727, 1666, 1599, 1444, 1165, 814 cm^-1.

(petroleum ether/ethyl acetate = 5:1) 0.33^D; ^OIH^{: 10}N^.1M⁰³R^9/C(⁹4^O00^B0M¹⁰²H⁸z^A,

CDCl₃) δ 7.61 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.53 (s,

1H), 4.33 – 4.19 (m, 2H), 3.75 (q, J = 52.4, 11.3 Hz, 1H), 3.40 (q, J

= 24.3, 16.0 Hz, 1H), 2.76 (q, J = 29.8, 11.3 Hz, 1H), 2.44 (s, 3H),

2.36 – 2.21 (m, 4H), 2.10 – 1.88 (m, 2H), 1.31 (m, 4H), 1.14 – 1.00

(m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 194.4, 167.1, 148.4, 143.7,

136.7, 133.7, 129.8, 127.5, 61.7, 46.7, 42.8, 26.5, 22.9, 21.8, 21.5,

19.4, 18.8, 14.0; HR-MS (ESI) calcd for [M + H]⁺: C₂₀H₂₆NO₅S:

392.1526, found: 392.1519; IR (KBr): 3009, 2925, 1724, 1655, 1631,

1400, 1166, 818 cm^-1.

Ethyl (E)-3-oxo-1-tosyloctahydro-2aH-cyclopropa[cd]indol-2a-

yl)meth- ylene) butanoate (3-2d). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

(cyclohex-2-en-1-yl)-4-methyl-N-(prop-2-yn-1-

yl)benzenesulfonamide (2e) (116.3 mg, 0.4 mmol), and purified by

column chromatography to give yellow oil (57.4 mg, 34%). R_f

(petroleum ether/ethyl acetate = 5:1) 0.34; H NMR (400 MHz,

CDCl₃) δ 7.70 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 6.34 (s,

1H), 4.32 (q, J = 6.3, 2.9 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 3.50 (d, J

1

= 11.5 Hz, 1H), 3.42 (d, J = 11.5 Hz, 1H), 2.44 (s, 3H), 2.37 (s, 3H), Ethyl

(E)-3-oxo-2-((3-tosyl-3-azabicyclo[4.1.0]heptan-6-

2.04 – 1.84 (m, 4H), 1.41 – 1.34 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H); yl)methylene)butanoate (3-2f). The title compound was prepared

¹³C NMR (101 MHz, CDCl₃) δ 201.3, 164.4, 149.5, 143.5, 135.7, from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and

134.6, 129.7, 127.2, 61.3, 55.9, 51.5, 34.4, 32.9, 31.3, 26.9, 25.5, enyne 2g (105.2 mg, 0.4 mmol), and purified by column

21.5, 16.7, 15.5, 14.1; HR-MS (ESI) calcd for [M + H]⁺: chromatography to give yellow oil (33.3 mg, 21%). R_f(petroleum

1

C₂₂H₂₇NO₅S: 418.1683, found: 418.1670; IR (KBr): 3009, 2925, ether/ethyl acetate = 5:1) 0.34; H NMR (400 MHz, CDCl₃) δ 7.61

1724, 1655, 1631, 1400, 1159, 818 cm^-1.

(d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.58 (s, 1H), 4.21 (q, J

= 7.1 Hz, 2H), 3.54 (d, J = 11.7 Hz, 1H), 3.12 (m, 2H), 2.61 (m, 1H),

2.43 (s, 3H), 2.37 (s, 3H), 1.99 (m, 1H), 1.89 (m, 1H), 1.30 – 1.24

(m, 4H), 0.98 – 0.93 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 201.9,

164.6, 152.0, 143.6, 134.5, 133.7, 129.8, 127.5, 61.3, 44.0, 42.3,

31.6, 27.9, 21.8, 21.5, 19.3, 18.7, 14.1; HR-MS (ESI) calcd for [M +

H]⁺: C₂₀H₂₆NO₅S: 392.1526, found: 392.1509; IR (KBr): 3009, 2924,

1727, 1655, 1631, 1400, 1164, 818 cm^-1.

Ethyl (Z)-3-oxo-1-tosyloctahydro-2aH-cyclopropa[cd]indol

-2a-yl)meth- ylene) butanoate (3-2d). The title compound was

prepared from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4

mmol)

and

N-(cyclohex-2-en-1-yl)-4-methyl-N-(prop-2-yn-1-

yl)benzenesulfonamide (2e) (116.3 mg, 0.4 mmol), and purified by

column chromatography to give yellow oil (85.4 mg, 51%). R_f

(petroleum ether/ethyl acetate = 5:1) 0.33; ¹H NMR (400 MHz,

CDCl₃) δ 7.68 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 6.21 (s,

1H), 4.37 – 4.29 (m, 2H), 4.26 (q, J = 6.2, 2.9 Hz, 1H), 3.60 (q, J =

28.2, 11.8 Hz, 2H), 2.43 (s, 3H), 2.21 (s, 3H), 2.06 – 1.91 (m, 4H),

1.47 – 1.34 (m, 7H); ¹³C NMR (101 MHz, CDCl₃) δ 193.9, 167.1,

149.0, 143.6, 135.4, 135.2, 129.8, 127.3, 61.8, 55.7, 50.8, 34.9, 33.3,

27.1, 26.9, 25.9, 21.5, 16.9, 15.6, 14.1; HR-MS (ESI) calcd for [M +

H]⁺: C₂₂H₂₇NO₅S: 418.1683, found: 418.1670; IR (KBr): 3009, 2925,

1724, 1655, 1631, 1400, 1159, 818 cm^-1.

Ethyl

(Z)-3-oxo-2-((3-tosyl-3-azabicyclo[4.1.0]heptan-6-

yl)methylene)butanoate (3-2f). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

allyl-N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide (2g) (105.2 mg,

0.4 mmol), and purified by column chromatography to give yellow

oil (47.1 mg, 30%). R_f(petroleum ether/ethyl acetate = 5:1) 0.33; ¹H

NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.0

Hz, 2H), 6.58 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.54 (d, J = 11.7 Hz,

1H), 3.12 (m, 2H), 2.61 (m, 1H), 2.43 (s, 3H), 2.37 (s, 3H), 1.99 (m,

1H), 1.89 (m, 1H), 1.30 – 1.24 (m, 4H), 0.98 – 0.93 (m, 2H); ¹³C

NMR (101 MHz, CDCl₃) δ 194.5, 167.3, 151.1, 143.7, 135.8, 133.6,

129.7, 127.6, 61.6, 44.1, 42.4, 27.3, 26.5, 21.5, 21.5, 19.2, 19.0, 14.0;

HR-MS (ESI) calcd for [M + H]⁺: C₂₀H₂₆NO₅S: 392.1526, found:

392.1509; IR (KBr): 3009, 2924, 1727, 1655, 1631, 1400, 1164, 818

cm^-1.

Ethyl

(E)-3-oxo-2-((3-tosyl-3-azabicyclo[4.1.0]heptan-5-

yl)methylene)butanoate (3-2e). The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

(but-3-en-1-yl)-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide (2f)

(105.2 mg, 0.4 mmol), and purified by column chromatography to

give yellow oil (41.1 mg, 26%). R_f(petroleum ether/ethyl acetate =

5:1) 0.34; ¹H NMR (400 MHz, CDCl₃) δ 7.53 (d, J = 8.2 Hz, 2H),

7.26 (d, J = 8.0 Hz, 2H), 6.53 (s, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.61

(d, J = 11.4 Hz, 1H), 3.25 (m, J = 10.4, 6.7, 3.3 Hz, 1H), 2.67 (d, J =

11.4 Hz, 1H), 2.36 (s, 4H), 2.29 (s, 2H), 2.28 – 2.27 (m, 1H), 1.95

(m, 1H), 1.87 – 1.79 (m, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.14 – 1.09

(m, 1H), 0.99 (q, J = 9.3, 4.2 Hz, 1H), 0.90 – 0.86 (m, 1H); ¹³C NMR

(101 MHz, CDCl₃) δ 201.7, 164.4, 149.0, 143.7, 135.5, 133.4, 129.7,

127.5, 61.4, 47.8, 42.7, 31.5, 22.9, 21.5, 21.5, 20.0, 18.9, 14.1; HR-

MS (ESI) calcd for [M + H]⁺: C₂₀H₂₆NO₅S: 392.1526, found:

392.1519; IR (KBr): 3009, 2925, 1724, 1655, 1631, 1400, 1166, 818

cm^-1.

Dimethyl

(E)-1-(2-(ethoxycarbonyl)-3-oxobut-1-en-1-

yl)bicyclo[3.1.0]hexane-3,3-dicarboxylate (3-2g). The title

compound was prepared from ethyl 2-diazo-3-oxobutanoate (1a)

(62.4 mg, 0.4 mmol) and diethyl 2-allyl-2-(prop-2-yn-1-yl)malonate

(2h) (84.3 mg, 0.4 mmol), and purified by column chromatography

to give yellow oil (28.1 mg, 21%). R_f(petroleum ether/ethyl acetate

= 5:1) 0.34; ¹H NMR (400 MHz, CDCl3) δ 6.53 (d, J = 18.5 Hz, 1H),

4.42 – 4.19 (m, 2H), 3.73 (d, J = 2.8 Hz, 3H), 3.70 (s, 3H), 2.76 –

2.26 (m, 7H), 1.72 (dd, J = 8.5, 4.9 Hz, 1H), 1.41 – 1.28 (m, 3H),

1.05 – 0.96 (m, 1H), 0.87 – 0.78 (m, 1H); ¹³C NMR (101 MHz,

CDCl3) δ 194.1, 172.7, 171.4, 167.8, 149.6, 134.9, 61.6, 59.5, 53.1,

36.9, 35.0, 30.7, 30.1, 26.4, 20.0, 14.0; HR-MS (ESI) calcd for [M +

H]⁺: C₁₇H₂₃O₇: 339.1366, found: 339.1367; IR (KBr): 3009, 2924,

1727, 1655, 1630, 1400, 1164, 818 cm^-1.

Ethyl

(Z)-3-oxo-2-((3-tosyl-3-azabicyclo[4.1.0]heptan-5-

yl)methylene)butanoate (3-2e). The title compound was prepared

according to general procedure A from ethyl 2-diazo-3-oxobutanoate

(1a) (62.4 mg, 0.4 mmol) and N-(but-3-en-1-yl)-4-methyl-N-(prop-2-

yn-1-yl)benzenesulfonamide (2f) (105.2 mg, 0.4 mmol), and purified

10 | J. Name., 2019, 00, 1-3

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Page 11 of 14

Organic & Biomolecular Chemistry

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Journal Name

Dimethyl

ARTICLE

(Z)-1-(2-(ethoxycarbonyl)-3-oxobut-1-en-1- Mechanism studies of this transformation

View Article Online

DOI: 10.1039/C9OB01028A

yl)bicyclo[3.1.0]hexane-3,3-dicarboxylate (3-2g). The title

compound was prepared from ethyl 2-diazo-3-oxobutanoate (1a)

(62.4 mg, 0.4 mmol) and diethyl 2-allyl-2-(prop-2-yn-1-yl)malonate

(2h) (84.2 mg, 0.4 mmol), and purified by column chromatography

to give yellow oil (31.1 mg, 23%). R_f(petroleum ether/ethyl acetate

= 5:1) 0.33; ¹H NMR (400 MHz, CDCl₃) δ 6.51 (s, 1H), 4.43 – 4.28

(m, 2H), 3.73 (s, 3H), 3.69 (s, 3H), 2.63 (m, J = 18.0, 14.7, 7.3 Hz,

3H), 2.54 – 2.45 (m, 1H), 2.26 (s, 3H), 1.78 – 1.71 (m, 1H), 1.38 (t,

J = 7.2 Hz, 3H), 1.03 (t, 1H), 0.86 (t, J = 5.7 Hz, 1H); ¹³C NMR (101

MHz, CDCl₃) δ 194.1, 172.7, 171.4, 167.8, 149.6, 134.9, 61.6, 59.4,

53.6, 53.1, 36.8, 35.0, 30.7, 30.1, 26.4, 20.0, 14.0; HR-MS (ESI)

calcd for [M + H]⁺: C₁₇H₂₃O₇339.1438, found: 339.1434; IR (KBr):

3009, 2924, 1727, 1655, 1630, 1400, 1164, 818 cm^-1.

Coupling-cyclization of 1a with d1-2a

d1-2a was produced according to previous literature.³¹d1-2a：¹H

NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.1

Hz, 2H), 5.73 (m, 1H), 4.09 (s, 2H), 3.83 (d, J = 6.5 Hz, 2H), 2.42 (s,

3H).

A Schlenk tube (20 mL) with a stirring bar was loaded with the

1a (62.4 mg, 0.4 mmol), d1-2a (100.4 mg, 0.4 mmol),

[Rh(COD)Cl]₂(9.9 mg, 5 mol %), dppp (16.5 mg, 10 mol %) and

dry toluene (2.0 mL) under an Ar atmosphere (1 atm). The reaction

mixture was then allowed to stir at 100 °C for 12 h. After cooling to

room temperature, the compound was purified by column

chromatography using petroleum ether/AcOEt (10:1) as eluent to

give the product d1-3-1a (E/Z = 31/44, 75 % overall yield).

Ethyl

(E)-3-oxo-2-((4-oxo-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

Coupling-cyclization of 1a with d2-2a

yl)methylene)butanoate (3-2h)

1

d2-2a was produced according to previous literature.³²d2-2a: H

The title compound was prepared from ethyl 2-diazo-3-oxobutanoate

(1a) (62.4 mg, 0.4 mmol) and N-(prop-2-yn-1-yl)-N-tosylacrylamide

(2i) (105.2 mg, 0.4 mmol), and purified by column chromatography

to give white solid (21.9 mg, 14%) m.p. 133.0-140 ^oC. R_f(petroleum

NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.1

Hz, 2H), 5.75 (m, 1H), 5.35 – 5.22 (m, 1H), 4.11 (d, J = 2.3 Hz, 2H),

3.85 (d, J = 6.4 Hz, 2H), 2.45 (s, 3H), 2.03 (t, J = 2.3 Hz, 1H).

A Schlenk tube (20 mL) with a stirring bar was loaded with the 1a

(62.4 mg, 0.4 mmol), d2-2a (100.4 mg, 0.4 mmol), [Rh(COD)Cl]₂

(9.9 mg, 5 mol %), dppp (16.5 mg, 10 mol %) and dry toluene (2.0

mL) under an Ar atmosphere (1 atm). The reaction mixture was then

allowed to stir at 100 °C for 12 h. After cooling to room temperature,

the compound was purified by column chromatography using

petroleum ether/AcOEt (10:1) as eluent to give the product d2-3a

(E/Z = 29/51, overall yield: 80 %).

1

ether/ethyl acetate = 5:1) 0.33; H NMR (400 MHz, CDCl₃) δ 7.89

(d, J = 7.9 Hz, 2H), 7.35 (d, J = 7.8 Hz, 2H), 6.57 (s, 1H), 4.25 (q, J

= 7.1 Hz, 2H), 4.03 (d, J = 10.5 Hz, 1H), 3.66 (d, J = 10.5 Hz, 1H),

2.45 (s, 3H), 2.42 (s, 3H), 2.10 (d, J = 6.2 Hz, 1H), 1.53 – 1.45 (m,

1H), 1.30 (t, J = 7.2 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃) δ 200.4,

170.5, 163.8, 145.5, 143.02, 137.9, 134.7, 129.8, 128.1, 61.9, 51.1,

31.1, 30.5, 24.3, 21.7, 19.9, 14.1; HR-MS (ESI) calcd for [M + H]⁺:

C₁₉H₂₂NO₆S: 392.1162, found: 392.1169; IR (KBr): 2976, 1726,

1595, 1450, 1366, 1152, 818, 740 cm^-1.

Ethyl

(Z)-3-oxo-2-((4-oxo-3-tosyl-3-azabicyclo[3.1.0]hexan-1-

Synthetic applications

yl)methylene)butanoate (3-2h) The title compound was prepared

from ethyl 2-diazo-3-oxobutanoate (1a) (62.4 mg, 0.4 mmol) and N-

(prop-2-yn-1-yl)-N-tosylacrylamide (2i) (105.2 mg, 0.4 mmol), and

purified by column chromatography to give white solid (36.1 mg,

23%) m.p. 133.0-140 ^oC. R_f(petroleum ether/ethyl acetate = 5:1)

0.30; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J = 8.1 Hz, 2H), 7.36 (d,

J = 7.8 Hz, 2H), 6.55 (s, 1H), 4.33 – 4.25 (m, 2H), 4.09 (d, J = 10.2

Hz, 1H), 3.81 (d, J = 10.2 Hz, 1H), 2.46 (s, 3H), 2.30 (s, 3H), 2.15 (d,

J = 8.6 Hz, 1H), 1.61 – 1.56 (m, 1H), 1.35 (t, J = 7.0 Hz, 4H). ¹³C

NMR (101 MHz, CDCl₃) δ 193.7, 170.4, 166.2, 145.5, 141.7,

138.3, 134.6, 129.8, 128.1, 62.2, 50.5, 30.2, 27.1, 24.4, 21.7,

19.9, 14.1; HR-MS (ESI) calcd for [M + H]⁺: C₁₉H₂₂NO₆S:

392.1162, found: 392.1169; IR (KBr): 2976, 1726, 1595, 1450, 1366,

1152, 818, 740 cm^-1.

A Schlenk tube (20 mL) with a stirring bar was loaded with the (Z)-

3-1a (151.1 mg, 0.4 mmol), CeCl₃•7H₂O (149.0 mg, 0.4 mmol), and

MeOH (2ml). Then NaBH₄(15.1 mg, 0.4 mmol) was added during

30 min and the reaction mixture was allowed to stir at room

temperature for 12 h. After cooling to room temperature, the mixture

is extracted with AcOEt (3×10 ml) and the organic layers are dried

with Νa₂SO₄and evaporated under reduced pressure. The residue

was purified by column chromatography using petroleum ether

/AcOEt = 2:1 (R_f= 0.3) as eluent to give the product (Z)-4 (67.4 mg,

44%).

Ethyl(Z)-3-hydroxy-2-((3-tosyl-3-azabicyclo[3.1.0]

hexan-1-

yl)methylene)butanoate (Z)-4. Yellow oil. ¹H NMR (400 MHz,

CDCl₃) δ 7.59 (d, J = 7.6 Hz, 2H), 7.26 (d, J = 7.6 Hz, 2H), 5.78 (s,

1H), 4.46 – 4.23 (m, 1H), 4.22 – 3.96 (m, 2H), 3.58 (d, J = 9.2 Hz,

1H), 3.46 (d, J = 9.2 Hz, 1H), 3.06 (d, J = 8.7 Hz, 1H), 2.90 (d, J =

9.2 Hz, 1H), 2.36 (s, 3H), 1.37 (s, 1H), 1.21 (t, J = 6.5 Hz, 6H), 0.85

(s, 1H), 0.74 (s, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 167.8, 143.6,

139.6, 133.8, 133.7, 133.6, 133.5, 129.7, 127.5, 69.4, 69.2, 61.0,

52.3, 49.6, 27.5, 27.5, 25.2, 22.3, 21.5, 15.7, 15.7, 14.2; HR-MS

(ESI) calcd for [M + H]⁺: C₁₉H₂₅NO₅S: 380.1526, found: 380.1530;

IR (KBr): 3026, 2982, 1725, 1698, 1633, 1456, 1165, 818 cm^-1.

Ethyl 6-phenyl-2-tosylisoindoline-5-carboxylate (3-2i). The title

compound was prepared from ethyl 2-diazo-3-oxobutanoate (1a)

(62.4 mg, 0.4 mmol) and 4-methyl-N,N-di(prop-2-yn-1-

yl)benzenesulfonamide (2j) (99.1 mg, 0.4 mmol), and purified by

column chromatography to give yellow solid (42.0 mg, 25%) m.p.

136.0-142 ^oC. R_f(petroleum ether/ethyl acetate = 5:1) 0.33; ¹H NMR

(400 MHz, CDCl₃) δ 7.71 (d, J = 8.2 Hz, 2H), 7.55 (s, 1H), 7.31 –

7.23 (m, 5H), 7.15 (dd, J = 7.4, 1.9 Hz, 2H), 7.09 (s, 1H), 4.60 (s,

4H), 3.96 (q, J = 7.1 Hz, 2H), 2.34 (s, 3H), 0.87 (t, J = 7.1 Hz, 3H);

¹³C NMR (101 MHz, CDCl₃) δ 168.3, 143.9, 142.6, 141.0, 139.4,

135.3, 133.6, 131.3, 129.9, 128.3, 128.1, 127.6, 127.4, 124.8, 124.0,

61.1, 53.7, 53.4, 21.5, 13.6; HR-MS (ESI) calcd for [M + H]⁺:

C₂₄H₂₄NO₄S: 422.1421, found: 422.1406; IR (KBr): 2919, 1727,

1633, 1549, 1400, 1169, 818, 750 cm^-1.

A Schlenk tube (20 mL) with a stirring bar was loaded with the (Z)-

3-1a (151.1 mg, 0.4 mmol), HBr aqueous (w_t% = 40 %, 81.0 mg,

0.4mmol) and MeOH (2.0 mL). Then the reaction mixture was

allowed to stir at room temperature for 24 h. After cooling to room

temperature, the mixture is extracted with CH₂Cl₂(3×10 ml) and the

J. Name., 2019, 00, 1-3 | 11

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ARTICLE

Journal Name

13 For selected reviews, see: (a) B. M. Trost, Acc. Chem. Res .

organic layers are dried with Νa₂SO₄and evaporated under reduced

pressure. The residue was purified by column chromatography using

cyclohexane/acetone (5:1) as eluent to give the product (Z)-5 (96.1

mg, 61%).

View Article Online

1990, 23, 34; (b) V. Michelet, P. Y. Toul_Dle_Oc_I:, ₁J₀. _.P₁₀. ₃G₉e_/Cn₉e_Ot,_BA₀n₁₀g₂e₈w_A.

Chem. Int. Ed. 2008, 47, 4268.

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J. Zhang, Angew. Chem., Int. Ed. 2016, 55, 14807; (b) Y. Wu, Z.

Ethyl

(Z)-2-((5-hydroxy-1-tosylpiperidin-3-yl)methylene)-3-

oxobutanoate (Z)-5: Yellow oil. ¹H NMR (400 MHz, CDCl₃) δ

13.00 (s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 5.88

(s, 1H), 4.22 (dd, J = 7.1, 3.7 Hz, 2H), 4.12 (dd, J = 9.1, 4.8 Hz, 1H),

3.89 (t, J = 10.4 Hz, 2H), 3.01 (d, J = 12.7 Hz, 1H), 2.90 (dd, J =

18.0, 8.5 Hz, 2H), 2.63 – 2.40 (m, 5H), 2.01 (s, 3H), 1.29 (t, J = 7.1

Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 174.5, 171.9, 144.0, 133.0,

132.1, 129.8, 127.7, 121.7, 97.3, 60.8, 53.3, 47.0, 44.7, 44.0, 21.6,

19.9, 14.3; HR-MS (ESI) calcd for [M + H]⁺: C₁₉H₂₅NO₅S: 396.1480,

found: 396.0096; IR (KBr): 3336, 3022, 2980, 1725, 1698, 1633,

1456, 1165, 816 cm^-1.

Chen, Y. Yang, W. Zhu, B. Zhou, J. Am. Chem. Soc. 2018, 140

42.

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1529.

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18 Z. Y. Chen, X. W. Hu, J. M. Huang, Zeng, W. Org. Lett. 2018,

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19 For selected examples, see: (a) J. Zhu, W. Hu, S. Sun, J. T. Yu,

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L. Wojtas, M. M. Kim, X. P. Zhang, J. Am. Chem. Soc. 2012,

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Acknowledgements

The authors thank NKRDPC (No. 2016YFA0602900), the NSFC

(No. 21871097), GPSF (No. 2017B090903003), and the GNSF (No.

2018B030308007) for financial support.

20 For selected examples, see: (a) Y. Su, Q. F. Li, Y. M. Zhao, P.

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Burya, B. V. Popp, C. Turro, C. Clementi, Z. T. Ball, Chem. Sci.

Notes and references

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9

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26 Naturally volatilizing the solvent of ethyl acetate/hexane (1:3;

v/v) solution of stronger polar isomer 3-1a at 25-30 ^oC

produced

a single crystal, which was unambiguously

R. Santhoshkumar, S. Mannathan, C. H. Cheng, J. Am. Chem.

Soc. 2015, 137, 16116.

confirmed to be (Z)-3-1a by its single-crystal X-ray analysis.

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isomers.

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32 H. Zhu, P. Chen, G. Liu, J. Am. Chem. Soc. 2014, 136, 1766..

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DOI: 10.1039/C9OB01028A

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DOI: 10.1039/C9OB01028A

Organic & Biomolecular Chemistry

PAPER

Rhodium(I)-Catalyzed Vinylation/[2+1] Carbocyclization of 1,6-

Enynes with -Diazocarbonyl Compounds

Junmin Huang,^§Xinwei Hu,^§Fengjuan Chen, Jiao Gui, and Wei Zeng *

Received 00th January 20xx,

Accepted 00th January 20xx

DOI: 10.1039/x0xx00000x

www.rsc.org/

Table of Content

A Rh(I)-catalyzed coupling-cyclization of enynes with diazo compounds has been developed to assemble versatile

vinyl-substituted azabicyclo[3.1.0]hexanes.

R¹R²

R³

H

R¹= R²= acyl, ester

R³= R⁴= R⁵= H, alkyl, aryl

X = N, C

R⁵

Rh(I) cat. (5 mol %)

dppp (10 mol %), Ar

toluene, 100 ^oC, 12 h

R¹R²

n

+

n

R⁴

X

N₂

R⁵m = n = 1 or 2

X

R³

m

R⁴

J. Name., 2013, 00, 1-3 | 1

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Article Doi

Rhodium(i)-catalyzed vinylation/[2 + 1] carbocyclization of 1,6-enynes with α-diazocarbonyl compounds

DOI: 10.1039/c9ob01028a

Source and publish data:

Authors:

Article abstract of DOI:10.1039/c9ob01028a

Full text of DOI:10.1039/c9ob01028a

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