An expedient, stereoselective synthesis of highly functionalized cyclic compounds

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An expedient, stereoselective synthesis of highly functionalized

cyclic compoundsy

a

Ewa Krawczyk, Krzysztof Owsianik, Aleksandra Skowronska,* Michał Wieczorek and

a

b

´

Wiesław Majzner^b

a

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences,

´ ´

Sienkiewicza 112, 90-363, Łodz, Poland. E-mail: askow@bilbo.cbmm.lodz.pl;

Fax: +48 (42) 684 7126; Tel: +48 (42) 681 8952

´ ´

Institute of General Food Chemistry, Technical University of Łodz,

b

´ ´

Stefanowskiego 4/10, 90-924 , Łodz, Poland

Received (in Montpellier, France) 6th August 2002, Accepted 15th October 2002

First published as an Advance Article on the web 12th November 2002

New thiophosphates containing functionalized cyclic ketone derivatives as ligands have been stereoselectively

prepared from readily available starting materials. Full axial stereoselectivity of the NaBH₄reduction

of the carbonyl group in thiophosphates providing the corresponding thiols or sulﬁdes has been demonstrated.

The sulﬁdes have been transformed into new functionalized cyclic Baylis–Hillman type adducts of deﬁned

conﬁguration. The prospects for the useful synthetic application of these adducts appear to be very promising.

The carbon–carbon double bond is one of the most important

functional groups in organic synthesis. Although numerous

methods have been reported for the preparation of unsatu-

rated compounds, stereoselective synthesis needs further

development. We have elaborated a novel strategy for the

stereoselective conversion of carbonyl compounds into unsatu-

rated ones.^1,2The key steps in this methodology involve for-

mation of the corresponding thiophosphates 2 and their

reactions with nucleophiles (Scheme 1).

Phosphates 2 are readily prepared from appropriate carbo-

nyl compounds, generally in very high yield.³The carbonyl

compounds are converted into silyl enol ethers and then addi-

tion of the thiophosphorylating agent dialkoxyoxophosphora-

nesulfenyl chloride 1 aﬀords thiophosphates 2. Addition of

a nucleophile to the carbonyl group in 2 involves formation

of the corresponding diastereoisomeric oxyanions 3. These

anions undergo rearrangement, involving migration of a phos-

phoryl group from sulfur to oxygen, aﬀording thiolate anions

4. Subsequent cyclization of 4 with elimination of phosphate

anion 5 provides the episulﬁdes 6. Spontaneous desulfurization

III

or desulfurization of 6 using P compounds gives the corre-

sponding oleﬁns 7. We have demonstrated that our methodol-

ogy is very useful in the synthesis of a variety of acyclic

Scheme 1

unsaturated compounds.^4–7

As part of a continuing programme of research we have

Results and discussion

Synthesis of thiophosphates 8 and 9

undertaken a study of the construction of exocyclic and endo-

cyclic carbon–carbon double bonds. Recently, we have elabo-

rated a ‘‘one-pot’’ procedure for the a-methylenation of

lactones, including racemic frullanolide and a-methylenecyclo-

alkanones.⁸In this paper we describe the synthesis of new thio-

phosphates 8 and 9 containing cyclic ligands and their further

synthetically useful transformations, involving also formation

of compounds containing an endocyclic unsaturated bond

(Scheme 2).

We decided to synthesize thiophosphates bearing cyclic

ligands, as well as this ligand containing diﬀerent substituents,

y Electronic supplementary information (ESI) available: crystallo-

graphic data tables described in the text. See http://www.rsc.org/

suppdata/nj/b2/b207700k/.

Scheme 2

DOI: 10.1039/b207700k

New J. Chem., 2002, 26, 1753–1767

1753

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in order to test their stereochemistry and synthetic utility.

Application of our method, previously used in the synthesis

of thiophosphates 2,³aﬀorded thiophosphates 8 and 9 in only

moderate yield. Therefore, we used a modiﬁed, two-step proce-

dure to prepare 8 and 9. Treatment of the corresponding

carbonyl compounds 10 and 11 with sodium hydride at 0 ^ꢀC

generated enolate anions 12 and 13. Thiophosphorylation of

these anions with dialoxyoxophosphoranesulfenyl chloride

(R¹¼ Et,^tBuCH₂) 1 provided thiophosphates 8 and 9 in good

to high yield (Scheme 3).

Addition of sulfenyl chloride 1 to enolate anions 13 is stereo-

selective, leading to a mixture of two diastereoisomers. The

resulting diastereoisomers could be easily separated by silica

gel column chromatography and each was subjected to further

transformations. However, some of them are not very stable

under chromatographic conditions. In these cases, we used

crude mixtures of diastereoisomers. The stereochemical dis-

tinction between isomers is illustrated in Fig. 1.

The question which arose was which isomer predominates,

by how much and under what circumstances. We established

the ratio of diastereoisomers on the basis of ³¹P NMR data.

We found that the main factors aﬀecting the ratio of stereoche-

mical products are the structure of the cyclohexanone element

and to some extent the solvent (see Table 1).

Fig. 1

The molecular structures of 9g and 9d are shown in Fig. 2

and 3, respectively. These results prompted us to assume that

the thiophosphorylation reagent approaches the enol anion

preferentially from the axial side. This is in agreement with

data reported in the literature.¹⁰

Reduction of thiophosphates 8 and 9 with sodium borohydride

The facial stereoselectivity of cyclohexanone derivatives, that

is axial or equatorial addition, has intrigued experimental

and theoretical chemists for a long time. The development of

methods for stereoselective reduction of the carbonyl group

continues to be of interest in organic chemistry.^11–13With this

background information we studied the stereochemical course

of reduction of the carbonyl group in a number of thiophos-

phates 8 and 9.

We ﬁrst investigated the reduction of thiophosphates 8a–c

having ﬁve-, six- and seven-membered rings, respectively.

Treatment of 8a with NaBH₄at ꢁ78 ^ꢀC led to the formation

of the thiol 14a as the unique product. The same reaction per-

formed in the presence of an excess of methyl iodate gave the

sulﬁde 17a in high yield. However, in the reaction of 8b and 8c

with the same reagents, episulﬁdes 15b,c as well as oleﬁns 16b,c

were formed, in addition to the major product, the thiols 14b,c

or sulﬁdes 17b,c (Scheme 4, Table 3). The small ring shows

high selectivity (entries 1 and 4) whereas larger rings produced

a mixture of compounds 14, 17 and 15, 16 (entries 2, 3, 5

and 6).

The conﬁguration of the major isomer was determined on

the basis of X-ray data and to some extent by ¹³C NMR (see

Table 2). X-Ray analysis of single crystals of 9g and 9d con-

ﬁrmed their anticipated molecular structures and revealed a

trans relationship between the equatorial 3-Me and 5-Ph sub-

stituents and the axial thiophosphates group (RO)₂P(O)S.

Inspection of the torsion angles and asymmetry parameters

reveals that the cyclohexane ring (C1,C2,C3,C4,C5,C6) adopts

a deformed chair conformation, with the C2 and C5 atoms in

the ﬂap positions.

The results of reduction of thiophosphates 9b–e contain-

ing additional substituents on the ring using NaBH₄and

NaBH₄–MeI are shown in Scheme 5 and Table 4. Reaction

of the pure major diastereoisomers 9b,d with these reagents

provided thiols 18b,d and sulﬁdes 21b exclusively (entries 1, 4

and 7). From the pure minor diastereoisomer 9d the unique

product was oleﬁn 20d (entry 5). From the mixture of diaster-

eoisomers of 9c,d,e, besides thiols 18c,e or sulﬁdes 21c,d,e, epi-

sulﬁdes 19c,d,e and oleﬁns 20c,d,e were formed, respectively

(entries 3, 6, 8–10).

We have also found that the reduction reaction of thiophos-

phates 8a–c and 9b in the presence of elemental iodine gave

the corresponding disulﬁdes 22a–d (Scheme 6).

Table 1 Addition of diethoxyoxophosphoranesulfenyl chloride 1 to

the enol anions 13

Ratio of diastereoisomers

R

Yield/%

d

³¹P

In THF

In diglime

3-Me

4-Me

77

90

88

63

52

4:1

3:1

5.4:1

3:1

21.0; 22.8

21.5; 22.5

20.8; 22.3

20.9; 22.4

21.4; 22.4

5-Ph

5-t-Bu

4,4,6-Me

5:1

6:1

2.5:1

1:1.2

3.5:1

1:3

Scheme 3

1754

New J. Chem., 2002, 26, 1753–1767

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Table 2 Selected ¹³C NMR data for thiophosphates 8 and 9

Compound

d C₁

³J_(C1P)^a/Hz

d C₃

³J_(C3P)^a/Hz

Major

208.1

201.2

202.4

209.0

204.9

200.3

201.8

202.8

200.8

Minor

Major

4.8

7.9

7.1

7.4

9.1

–

Minor

Major

35.9

39

Minor

Major

–

Minor

8a

8b

8c

9a

9b

9c

9d

9e

9f

2.8

2.4

–

34.4

42.4

37.1

37.8

42.9

37.7

38.4

208.7

202.5

200.3

200.4

201.2

202.3

–

42.9

39.7

34.6

46.9

40.5

37.0

12.0

–

8.6

–

5.1

4.3

4.6

5.1

4.9

3.3

–

9.2

8.8

–

6.5

5.8

–

3.4

9.7

a

see ref. 9.

The ratio and the structure of all compounds obtained were

1

between two conformers 26 and 26a with formation of the epi-

sulﬁde 19b. The latter undergoes spontaneous desulfurization

to aﬀord the cyclohexene derivative 20b. In the intermediate

compound 26a the phosphate group and thiolate anion are

in anti positions (Scheme 8).

assigned on the basis of H, ¹³C and ³¹P NMR data.

The discussed transformations of thiophosphates 8 and 9

can be rationalized on the basis of the following mechanistic

schemes (Schemes 7 and 8), which are in agreement with the

mechanism proposed by us for the reaction of nucleophilic

reagents with thiophosphates 2 containing all acyclic substitu-

ents (see Scheme 1).

The approach of a nucleophile of small bulk from the axial

side gives, for example, from the major diastereoisomer of

thiophosphate 9b the oxyanion 23 of conﬁguration shown in

Scheme 7. The next step involves migration of the phosphoryl

group from sulfur to oxygen aﬀording thiolate anion 24. There

is no possibility of cyclization via nucleophilic attack of anion

24 on the carbon atom with elimination of the phosphate

group and formation of episulﬁde, since thiolate anion and

phosphate group cannot adopt the anti position. Therefore,

the ﬁnal product is the thiol 18b (after protonation of thiolate

anion under reaction conditions) or the sulﬁde 21b (after

methylation).

In the case of the minor isomer of thiophosphate 9e contain-

ing a 5-^tBu substituent, we observed the formation of oleﬁn. It

seems to be reasonable to assume that a cyclization reaction is

also possible if this thiolate anion changes its chair conforma-

tion into a twist one. In both diastereoisomers of 9, when the

thiophosphate function adopts the axial as well as equa-

torial dispositions, only the products resulting from the axial

approach of the reducing agent are observed. Therefore,

stereoelectronic eﬀects must be considered in addition to steric

eﬀects to explain the observed products. Equatorial approach

of the reduction reagent to the carbonyl group in both the

major and minor diastereoisomers of thiophosphates 9 can

be excluded. Such an approach should provide diﬀerent com-

pounds. In the case of the major diastereoisomers of 9, the pro-

ducts must be functionalized cyclic oleﬁns, whereas in the case

of minor diastereoisomers of 9, these are thiols of diﬀerent con-

ﬁguration with respect to the thiols 18 obtained by us from the

major diastereoisomers of 9 (see NMR data in Table 5 and the

X-ray structure of 28d in Fig. 4). The ¹H NMR data, collected

in Table 5, for 18 (in particularly the characteristic values of

The oxyanion 25 obtained from the axial reduction of the

minor diastereoisomer of 9b undergoes also rearrangement

involving migration of the phosphoryl group from sulfur to

oxygen giving thiolate anion 26. In spite of the diequatorial

positions of the phosphate substituent and thiolate anion, this

intermediate 26 is able to undergo cyclization via equilibrium

3

axial J_H1H2and equatorial J_H1H2coupling constants in the

Fig. 2 Thermal ellipsoidal view with the atom numbering scheme of

compound 9g. Ellipsoids are shown with 50% probability.

Fig. 3 Thermal ellipsoidal view with the atom numbering scheme of

compound 9d. Ellipsoids are shown with 50% probability.

New J. Chem., 2002, 26, 1753–1767

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Scheme 5

Scheme 4

range 9–12 Hz and 4.5–5.0 Hz, respectively) strongly sup-

ported the conﬁguration of thiols 18.

sphorylating reagent to the enol anions generated from the

corresponding cyclohexanone derivatives. They constitute

interesting models for investigation of the reduction reaction

of the carbonyl group in 8 and 9. We have demonstrated that

the reduction reaction, using NaBH₄, of thiophosphates 9

exhibits full axial selectivity, providing thiols 18 or sulﬁdes

21 and episulﬁdes 19 and oleﬁns 20. Compounds 17 and

21 are useful precursors of new cyclic Baylis–Hillman type

adducts 29 and 30. Our synthetic approach to these adducts

involves reduction of the carbonyl group in readily available

thiophosphates 8 and 9 by NaBH₄in the presence of MeI, sub-

sequent oxidation of intermediate sulﬁdes 17, 21 to sulfoxides

27, 28 and cis elimination of the latter to aﬀord the desired

adducts of deﬁned stereochemistry. The multifunctionality of

our new cyclic adducts obtained makes them attractive for

numerous further important transformations. The regio- and

stereoselectivity of their reactions with various nucleophiles

are currently under investigation.

Synthesis of novel cyclic Baylis–Hillman type adducts

Baylis–Hillman adducts are very useful in organic synthesis.

They undergo a variety of transformations involving regio-

and stereochemical control. The usefulness of these adducts

has been demonstrated by a number of reactions and applica-

tions.^14–16However, more can be done to advance these

fascinating reactions. Several methods have been devised for

the preparation of acyclic Baylis–Hillman adducts.¹⁶Surpris-

ingly, only two syntheses of such cyclic adducts has been

reported.¹⁷Therefore, it was interesting to determine the utility

of intermediate sulﬁdes 17 and 21 as convenient precursors of

sterically deﬁned novel cyclic Baylis–Hillman type adducts.

Indeed, we found that treatment of the sulﬁdes 17 and 21 with

1.1 equiv. of m-CBPA in CH₂Cl₂at ꢁ78 ^ꢀC provided sulfox-

ides 27 and 28 in very good yield. The latter after puriﬁcation

is easily and eﬃciently converted (via cis elimination) under

thermal conditions into the corresponding adducts. We

obtained the best results when transformation of the starting

bicarbonyl compounds 10 and 11 into sulfoxides 27 and 28

was performed using crude intermediate thiophosphates 8

and 9 and sulﬁdes 17 and 21 (Schemes 9 and 10).

Suitable crystals of the sulfoxide 28d were obtained for an

X-ray structure determination to establish the relative stereo-

chemistry (Fig. 4). The X-ray analysis revealed a trans relation

between the phosphate and carboester groups. Therefore, this

shows good agreement with the stereochemistry of the product

21d obtained via reduction of the carbonyl group in the major

diastereoisomer of thiophosphate 9d. These results additionally

supported axial selectivity in the addition of reductive agent to

the carbonyl group in thiophosphates 9. The cyclohexane ring

(C1,C2,C3,C4,C5,C6) of 28d adopts a deformed chair confor-

mation with the C1 and C4 atoms in the ﬂap positions.

Experimental

General

¹H, ¹³C and ³¹P NMR spectra were recorded on a Bruker AC

200 spectrometer at 200.13, 50.32 and 81.02 MHz, respectively

(using deuterochloroform as solvent), unless otherwise noted.

IR spectra were measured on an Ati Mattson Inﬁnity FT

IR60. MS spectra (EI, CI and HR) were recorded on a Finni-

gan MAT 95 spectrometer. Microanalyses were obtained on a

Carlo Erba CHNS-OEA 1108 elemental analyzer.

Chromatographic puriﬁcation was performed on silica gel

columns (Merck, Kieselgel 60 and 70–230 mesh) with indicated

eluents. PLC was carried out on silica gel plates (Merck F₂₅₄).

Chemicals and solvents were obtained from commercial

sources and used as received or dried according to standard

a b

Table 4 Reactions of thiophosphates 9 with NaBH₄

and with

NaBH₄in the presence of an excess of MeI^c

Conclusions

In conclusion, we have obtained new types of thiophosphates 8

and 9 via stereoselective addition of an electrophilic thiopho-

Entry

Thiophosphate 9

Products (% yield)

1

2

9b^d

9b^e

9c^f

9d^d

9d^e

9e^g

9b^d

9c^f

9d^f

9e^g

18b (90)

–

19b (60)^b

20b (30)^a

20c (20)

–

a

Table 3 Reactions of thiophosphates 8 with NaBH₄and with

NaBH₄in the presence of an excess of MeI^b

3

18c (60)

18d (85)

–

4

–

5

–

20d (60)

20e (25)

–

Entry

Thiophosphate 8

Products (% yield)

6

18e (71)

21b (99)

21c (62)

21d (60)

21e (60)

–

1

2

3

4

5

6

8a

8b

8c

8a

8b

8c

14a (85)

14b (89)

14c (49)

17a (72)

17b (79)

17c (70)

–

16b (11)

16c (31.5)

7

–

8

19c (15)

19d (15)

19e (25)

20c (10)

20d (15)

–

15c (6.5)

–

9

10

–

16b (12)

15b (8.0)

15c (24)

a

Reaction conditions: NaBH₄(2 equiv), solvent MeOH–CH₂Cl₂(1:1),

b

–

temp. ꢁ78 ^ꢀC, time 3 h. NaBH₄(2 equiv) solvent MeOH–CH₂Cl₂

a

c

Reaction conditions: NaBH₄(2 equiv), solvent MeOH–CH₂Cl₂(1:1),

b

(1:1), temp. 0 ^ꢀC, time 1 h. NaBH₄(2 equiv) MeI (5 equiv), solvent

temp. ꢁ78 ^ꢀC, time 3 h. NaBH₄(2 equiv) MeI (5 equiv), solvent

MeOH–CH₂Cl₂(1:1), temp. ꢁ78^ꢀ! r.t., time 3 h (ꢁ78 ^ꢀC) and 3–5 h

MeOH–CH₂Cl₂(1:1), temp. ꢁ78^ꢀ! r.t., time 3 h (ꢁ78 ^ꢀC) and 3–5

h (ꢁ78^ꢀ! r.t.).

(ꢁ78^ꢀ! r.t.). ^dMajor diastereomer. ^eMinor diastereomer ^f.Major +

g

minor (3:1) diastereomers. Major + minor (2.5:1) diastereomers.

1756

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Scheme 6

methods. b-Ketoesters¹⁸and dialkoxyoxophosphoranesulfenyl

chlorides 1¹⁹were prepared as described.

Scheme 8

Crystallography

128.7 h for compound 28d; intensity corrections were applied

(DECAY program).²⁰An empirical absorption correction

was applied by the use of the c-scan method (EAC pro-

gram).^20,21A total of 4459 (9g), 4109 (9d) and 4577 (28d)

observed reﬂections with I q 0s(I) were used to solve the struc-

ture by direct methods and to reﬁne it by full matrix least-

squares methods using F².^22,23Hydrogen atoms were placed

geometrically at idealised positions, and set as riding with ﬁxed

thermal parameters equal to 1.33 times the equivalent isotropic

thermal parameter of the parent atom. Anisotropic thermal

parameters were reﬁned for all nonhydrogen atoms. For com-

pound 9g the ﬁnal calculation converged to R ¼ 0.0503 for

262 reﬁned parameters and 3385 observed reﬂections with

I q 2s(I) while performing a racemic twinning reﬁnement

[the Flack absolute structure parameter w ¼ 0.48(3)^24,25]. For

compound 9d the ﬁnal reﬁnement converged to R ¼ 0.0484

for 249 reﬁned parameters and 3553 observed reﬂections with

I q 2s(I) with inclusion of the extinction parameter in the

reﬁnement [the obtained value of the extinction parameter

was 0.00099(9)]. For compound 28d the ﬁnal reﬁnement con-

verged to R ¼ 0.0570 for 267 reﬁned parameters and 4089

observed reﬂections with I q 2s(I) with inclusion of the extinc-

tion parameter in the reﬁnement [the obtained value of the

extinction parameter was 0.00017(3)]. The conformation of

the six-membered ring was determined on the basis of the

Compound 9g crystallises in the orthorhombic system, in space

group P2₁2₁2₁with the unit cell consisting of four molecules.

Compound 9d and 28d each crystallise in the monoclinic sys-

tem, in space groups C2/c and P2₁/n, respectively. The unit

cell consists of eight molecules for compound 9d and of four

molecules for compound 28d. In all three compounds the

six-membered ring C1,C2,C3,C4,C5,C6 adopts a slightly

deformed chair conformation with the ﬂap position atoms

being C1 and C4 for compound 28d and C2, C5 for the other

two compounds. The overall view of the molecules with the

atom numbering scheme can be seen respectively in Figs. 2, 3

and 4. In Tables S1, S2 and S3 (Electronic supplementary

information, ESI) comparison of selected bond lengths, bond

angles and torsional angles are present. In the analysed crystal

structures several weak C–Hꢂ ꢂ ꢂO contacts occurs (Table S4,

ESI).

The crystal and molecular structures of all three compounds

were determined using data collected at room temperature on a

CAD4 diﬀractometer with graphite monochromated CuKa

radiation. Crystal data and experimental details are shown in

Table 6. The lattice constants were reﬁned by least-squares ﬁts

of 25 reﬂections in the y range 15.44^ꢀ–30.48^ꢀfor compound

9g, 21.86^ꢀ–27.67^ꢀfor compound 9d and 20.38^ꢀ–27.55^ꢀfor

compound 28d. The decline in intensities of three control

reﬂections (2,3,ꢁ4; 2,4,0; 2,ꢁ3,ꢁ6 for 9g, ꢁ3,1,11; ꢁ3,0,9;

ꢁ4,5,ꢁ4 for 9d and ꢁ4,2,7; ꢁ1,2,ꢁ7; 3,5,3 for 28d) was

15.6% during 184.6 h of exposure time for compound 9g,

3.5% during 111.7 h for compound 9d; and 27.9% during

1

Table 5 Selected {³¹P}¹H NMR and H NMR data for thiols 14, 18

and disulﬁdes 22a,b

Tiols 14, 18 and

disulﬁdes 22

³J_H1(ax)H2(ax)

Hz

/

³J_H1(ax)H2(eq)

Hz

/

³J_H1P

/

Hz

d H1

14a

14b

14c

18b

18c

18d

18e

18g

22a

22b

4.97

4.84

4.94

4.51

4.79

4.92

4.76

4.50

5.03

4.94

6.5

7.5

6.5

3.0

2.5

–

6.5

14.6

8.1

8.9

6.4

7.7

6.3

9.3

5.4

7.0

8.1

9.9

11.3

12.1

11.5

9.3

4.5

4.9

5.0

–

9.9

15.2

4.6

3.5

Scheme 7

New J. Chem., 2002, 26, 1753–1767

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Fig. 4 Thermal ellipsoidal view with the atom numbering scheme of

compound 28d. Ellipsoids are shown with 50% probability.

Scheme 10

torsion angles, calculation of the asymmetry parameters,^26,27

and also by dihedral angles between selected least-squares

planes²⁸(see Tables S5 and S6 in the ESI). Data corrections

was carried out with the Enraf-Nonius SDP crystallographic

computing package,²⁰structure solution with SHELXS²¹and

structure reﬁnement with SHELXL.²²

CCDC numbers 195722–24. See http://www.rsc.org/supp-

data/nj/b2/b207700k/ for crystallographic ﬁles in CIF or

other electronic format.

in tetrahydrofurane (1 mL). Immediately after addition (30 min)

the reaction mixture was cooled to ꢁ78 ^ꢀC and was added drop-

wise a solutionof freshly prepared dialkoxyoxophosphoranesul-

fenyl chloride 1 (0.61 g, 3 mmol) in tetrahydrofuran (2 mL).

Stirring was continued for 20 min (TLC analysis) and water–

pentane–ether (1:1:1, 20 mL) was added to the reaction mixture.

The organic layer was separated and the water layer was

extracted with pentane–ether (1:1, 3 ꢃ 5 mL). The organic

extracts were washed with NaHCO₃(8 mL), water (5 mL)

and dried over MgSO₄. Evaporation followed by column

chromatography (petroleum ether–ethyl acetate 3:1), aﬀorded

pure thiophosphates 8 and 9 as colourless oils.

Syntheses

Thiophosphates 8 and 9. General procedure. To a stirred sus-

pension of dry sodium hydride (0.12 g, 5 mmol) in dry tetrahy-

drofurane (10 mL) was added by syringe at 0 ^ꢀC under argon

atmosphere a solution of the appropriate b-ketoester (3.3 mmol)

Table 6 Crystal data and experimental details

Compound

9g

Compound

9d

Compound

28d

Molecular formula

Formula weight

Crystallographic

system

C₂₀H₃₇O₆PS

436.53

Orthorhombic

C₁₉H₂₇O₆PS

414.44

Monoclinic

C₂₀H₃₁O₇PS

446.48

Monoclinic

Space group

˚

P2₁2₁2₁

6.075(2)

19.042(5)

20.889(8)

90.00

C2/c

P2₁/n

a/A

˚

17.797(12)

10.521(4)

23.330(12)

106.53(5)

4188.0(38)

8

13.705(3)

11.378(2)

15.252(3)

103.02(3)

2317.2(8)

4

b/A

˚

c/A

b /^ꢀ

3

˚

U/A

2416.4(14)

4

2.069

Z

m/cm^ꢁ1

2.369

2.209

˚

l/A

T/K

1.54184

293(2)

4976

1.54184

293(2)

4315

1.54184

293(2)

4757

Unique reﬂect.

Reﬂect. [I > 0s(I)]

Obs. reﬂect.

[I > 2s(I)]

R_int

4459

3385

4109

3553

4577

4089

0.0837

0.0503

0.1136

0.0731

0.0484

0.1358

0.0384

0.0570

0.1641

R_obs

wR_obs

a

Weighting scheme w ¼ [s²(F_o²) + (mP)²+ nP]^ꢁ1where P ¼

(F_o²+ 2F_c²)/3.

Scheme 9

1758

New J. Chem., 2002, 26, 1753–1767

View Article Online

3

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-2-oxocycloptanecar-

2.54 (dd, J_HH¼ 10.0 Hz, J_HH¼ 6.3 Hz, 2H, CH₂), 3.34

1

3

boxylate (8a). H NMR (CDCl₃): d 1.25 (t, J_HH¼ 7.1 Hz,

(ddq, J_HH¼ 6.4 Hz, J_HH¼ 6.3 Hz, J_HH¼ 6.1 Hz, 1H,

CHCH₃), 3.97–4.19 (m, 4H, OCH₂CH₃). ³¹P NMR (CDCl₃):

d 23.7. ¹³C NMR (CDCl₃): d 14.5 (s, CHCH₃), 15.5, 15.7 (s,

3

4

3H, COCH₂CH₃), 1.32 (dt, J_HH¼ 7.1 Hz, J_HP¼ 0.9 Hz,

6H, POCH₂CH₃), 1.98–2.20 (m, 2H, CH₂), 2.28–2.87 (m,

¼

3

4H, CH₂), 4.06–4.26 (m, 4H, POCH₂CH₃), 4.19 (q, J_HH

3

OCH₂CH₃), 21.3 (s, CH₂), 25.2 (d, J_CP¼ 10.0 Hz, CCH₃),

7.1 Hz, 2H, COCH₂CH₃). ³¹P NMR (CDCl₃): d 22.0. ¹³C

36.7 (s, CH₂), 39.7 (s, CH), 42.9 (d, J_CP¼ 12.0 Hz, CH₂),

3

2

NMR (CDCl₃): d 13.4 (s, COCH₂CH₃), 15.4 (d, J_CP¼ 7.1

59.8 (s, CS), 63.51, 63.52 (d, J_C_ꢁP1¼ 7.0 Hz, POCH₂CH₃),

=

1254 s (P O), 1712 s

Hz, POCH₂CH₃), 19.2, 35.9, 36.8 (s, CH₂), 62.3 (s,

208.7 (s, C O). IR (ﬁlm): n/cm

2

+

=

COCH₂CH₃), 63.6 (d, J_CP¼ 6.2 Hz, POCH₂), 167.4 (d,

(C O). MS (CI-isobutane): m/z (%) 295 (100) [M + H] .

HRMS (CI) calcd for C₁₂O₄H₂₃PS + H [M + H]⁺295.1136;

found: 295.1135. Yield: 29%. R_f(ethyl acetate–petroleum ether

1:2) ¼ 0.44.

3

³J_CP¼ 8.3 Hz, COC_ꢁH₁₂CH₃), 208.1 (d, J_CP¼ 4.8 Hz,

=

C O). IR (ﬁlm): n/cm 1255 s (P O), 1732 s (C O), 1760

+

s (EtC O). MS (CI-isobutane): m/z (%) 325 (100) [M + H] .

=

Anal. calcd for C₁₂H₂₁O₆PS (324.37): C, 44.44; H, 6.53; P,

9.55; S, 9.88; found: C, 44.64; H, 6.71; P, 9.24; S, 9.55%. Yield:

82%. R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.30.

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-3-methyl-2-oxocyclo-

hexanecarboxylate (9b). The ratio of diastereoisomers is 4:1.

¼

Major isomer of 9b: ¹H NMR (CDCl₃): d 1.00 (d, J_HH

3

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-2-oxocyclohexanecar-

6.5 Hz, 3H, CHCH₃), 1.32 (t, J_HH¼ 7.0 Hz, POCH₂CH₃),

1

3

boxylate (8b). H NMR (CDCl₃): d 1.30 (t, J_HH¼ 7.2 Hz,

1.33 (t, J_HH¼ 6.0 Hz, COCH₂CH₃), 1.36–1.88 (m, 2H,

3

3H, COCH₂CH₃), 1.33 (t, J_HH¼ 6.3 Hz, 6H, POCH₂CH₃),

CH₂), 2.05–2.27 (m, 2H, CH₂), 2.53–2.66 (m, 2H, CH₂), 3.09

(m, CH), 4.10–4.35 (m, 6H, OCH₂CH₃). ³¹P NMR (CDCl₃):

d 21.0. ¹³C NMR (DEPT, CDCl₃): d 13.9 (s, CH₃), 14.7 (s,

1.70–2.08 (m, 4H, CH₂), 2.15 (ddd, J_HH¼ ³J_HH¼ 12.7 Hz,

3

³J_HH¼ 4.3 Hz, 1H, CH₂), 2.48 (ddd, J_HH¼ ³J_HH¼ 14.1

3

Hz, J_HH¼ 5.7 Hz, 1H, CH₂), 2.65 (m, 1H, CH₂), 3.03 (m,

COCH₂CH₃), 15.8 (d, J_CP¼ 7.1 Hz, POCH₂CH₃), 20.8,

1H, CH₂), 4.05–4.40 (m, 6H, OCH₂CH₃). ³¹P NMR (CDCl₃):

d 22.2. ¹³C NMR (CDCl₃): d 13.8 (s, COCH₂CH₃), 15.9 (d,

³J_CP¼ 7.1 Hz, POCH₂CH₃), 22.9, 26.8 (s, CH₂), 39.0 (d,

³J_CP¼ 2.8 Hz, CH₂), 40.4 (s, CH₂), 62.6 (s, COCH₂CH₃),

36.5 (s, CH₂), 37.1 (d, J_CP¼ 5.1 Hz, CH₂), 41.8 (s, CH),

3

2

62.3 (s, COCH₂CH₃), 64.0, 64.2 (d, J_CP¼ 7.1 Hz,

2

POCH₂CH₃), 67.2 (d, J_CP¼ 5.0 Hz, CS), 168.8 (s,

3

=

COCH₂CH₃), 204.9 (d, J_CP¼ 9.1 Hz, C O). IR (ﬁlm):

n/cm^ꢁ11254 s (P O), 1716 s (C O), 1739 s (EtC O). MS (EI,

70 eV): m/z (%) 352 (8) [M]⁺, 182 (100) [MꢁHSP(O)(OEt)₂]⁺,

171 (45), 138 (85), 109 (36), 81 (81), 55 (86), 43 (47), 39 (37).

Anal. calcd for C₁₄H₂₅O₆PS (352.42): C, 47.71; H, 7.16; P,

8.79; S, 9.10; found: C, 47.21; H, 7.21; P, 8.66; S, 8.75%. Yield:

62%. R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.26. Minor iso-

2

=

64.1 (d, J_CP¼ 6.1 Hz, POCH₂CH₃), 67.6 (s, CS), 167.8 (s,

3

=

COCH₂CH₃), 201.2 (d, J_CP¼ 7.9 Hz, C O). IR (ﬁlm):

n/cm^ꢁ11240 s (P O), 1721 s (C O), 1725 s (EtC O). MS

(CI-isobutane): m/z (%) 339 (100) [M + H]⁺, 293 (25). Anal.

calcd for C₁₃H₂₃O₆PS (338.39): C, 46.15; H, 6.85; P, 9.15; S,

9.48; found: C, 46.00; H, 6.82; P, 9.39; S, 9.33%. Yield: 93%.

R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.22.

=

mer of 9b:¹H NMR (CDCl₃): d 1.09 (d, J_HH¼ 6.4 Hz, 3H,

3

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-2-oxocycloheptanecar-

CHCH₃), 1.15–1.42 (m, 9H, OCH₂CH₃), 1.66–2.10 (m, 5H,

CH₂), 2.55 (m, 1H, CH₂), 3.45 (m, 1H, CH), 4.10–4.35 (m,

6H, OCH₂). ³¹P NMR (CDCl₃): d 22.8. ¹³C NMR (CDCl₃):

1

3

boxylate (8c). H NMR (CDCl₃): d 1.30 (t, J_HH¼ 6.9 Hz,

3

4

3H, COCH₂CH₃), 1.34 (dt, J_HH¼ 7.1 Hz, J_HP¼ 1.0 Hz,

6H, POCH₂CH₃), 1.50–1.91 (m, 6H, CH₂), 2.46–2.80 (m,

4H, CH₂), 4.05–4.35 (m, 6H, OCH₂CH₃). ³¹P NMR (CDCl₃):

d 22.5. ¹³C NMR (CDCl₃): d 12.8 (s, COCH₂CH₃), 14.9 (d,

³J_CP¼ 6.8 Hz, POCH₂CH₃), 23.6, 25.0, 28.5 (s, CH₂), 34.4

3

d 13.7 (s, CH₃), 14.9 (s, COCH₂CH₃), 15.8 (d, J_CP¼ 7.4

Hz, POCH₂CH₃), 23.2, 35.9, 39.7, (s, CH₂), 44.4 (s, CH),

2

62.9 (s, COCH₂CH₃), 64.0 (d, J_CP¼ 6.4 Hz, POCH₂CH₃),

3

67.5 (s, CS), 168.3 (s, COCH₂CH₃), 202.5 (d, J_CP¼ 8.7 Hz,

3

ꢁ1

=

(d, J_CP¼ 2.4 Hz, CH₂CS), 61.4 (s, COCH₂CH₃), 62.7, 63.0

C O). IR (ﬁlm): n/cm 1256 s (P O), 1714 s (C O), 1739

2

+

=

(d, J_CP¼ 6.4 Hz, POCH₂CH₃), 69.6 (s, CS), 167.4 (s,

s (EtC O). MS (EI, 70 eV): m/z (%) 352 (10) [M] , 182

3

=

COCH₂CH₃), 202.4 (d, J_CP¼ 7.1 Hz, C O). IR (ﬁlm):

(100) [MꢁHSP(O)(OEt)₂)]⁺, 269 (39), 171 (72), 155 (24), 136

(33), 109 (31), 81 (42), 55 (39), 41 (28). Anal. calcd for

C₁₄H₂₅O₆PS (352.42): C, 47.71; H, 7.16; P, 8.79; S, 9.10;

found: C, 47.49; H, 7.01; P, 8.53; S, 8.84%. Yield: 15%. R_f

(ethyl acetate–petroleum ether 1:2) ¼ 0.23.

n/cm^ꢁ11247 s (P O), 1712 s (C O), 1738 s (EtC O). MS

(EI, 70 eV): m/z (%) 352 (32) [M]⁺, 171 (100) [H +

HSP(O)(OEt)₂]⁺, 155 (37), 109 (47), 81 (49). Anal. calcd for

C₁₄H₂₅O₆PS (352.43): C, 47.73; H, 7.15; P, 8.79; S, 9.10;

found: C, 47.98; H, 7.39; P, 9.06; S, 8.40%. Yield: 78%. R_f

(ethyl acetate–petroleum ether 1:5) ¼ 0.34.

=

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-4-methyl-2-oxocyclo-

hexanecarboxylate (9c). The ratio of diastereoisomers is 3:1.

1

S-(1,3-Dimethyl-2-oxocyclohexyl)-O,O-diethyl thiophosphate

(9a). The ratio of diastereoisomers is 2.8:1. Major isomer of

9a: ¹H NMR (CDCl₃): d 0.99 (d, ³J_HH¼ 6.5 Hz, 3H, CHCH₃),

Mixture of two isomers of 9c: H NMR (CDCl₃): d 0.94 (d,

³J_HH¼ 6.4 Hz, 3H, CHCH₃, major), 0.97 (d, J_HH

¼

3

6.9 Hz, 3H, CHCH₃, minor), 1.20 (t,³J_HH¼ 7.1 Hz, 6H,

3

1.26 (t, J_HH¼ 7.0 Hz, COCH₂CH₃), 1.73 (s, 3H, CCH₃),

COCH₂CH₃), 1.26 (t, J_HH¼ 7.0 Hz, 12H, POCH₂CH₃),

1.90–2.05 (m, 2H, CH₂), 2.24 (dd, J_HH¼ ³J_HH¼ 13.2 Hz,

1.52–2.30 (m, 10H, CH₂), 2.53 (m, 3H, CH₂), 3.12 (m, 1H,

CH₂), 3.85–4.40 (m, 12H, OCH₂). ³¹P NMR (CDCl₃): d 21.5

(major), 22.5 (minor). ¹³C NMR (DEPT, CDCl₃): d 13.6 (s,

3

³J_HH¼ ³J_HH¼ 5.5 Hz, 2H, CH₂), 2.54 (dd, J_HH¼ 10.0

3

Hz, J_HH¼ 6.3 Hz, 2H, CH₂), 2.59 (ddq, J_HH¼ 6.4 Hz,

³J_HH¼ 6.3 Hz, J_HH¼ 6.0 Hz, 1H, CHCH₃), 3.94–4.18 (m,

COCH₂CH₃), 15.7 (d, J_CP¼ 7.2 Hz, POCH₂CH₃), 20.2 (s,

3

4H, OCH₂CH₃). ³¹P NMR (CDCl₃): d 25.1. ¹³C NMR

(CDCl₃): d 14.9 (s, CHCH₃), 15.5, 15.7 (s, OCH₂CH₃), 21.9

(s, CH₂), 25.3 (s, CCH₃), 35.1 (s, CH₂), 41.1 (s, CH), 42.4 (s,

CCH₃, minor), 21.7 (s, CCH₃, major), 28.9 (s, CH₂, major),

29.4 (s, CH₂, minor), 31.4 (s, CH₂), 33.5 (s, CHCH₃, minor),

34.3 (s, CHCH₃, major), 34.6 (d, ³J_CP¼ 3.3 Hz, CH₂, minor),

2

3

CH₂), 57.8 (d, J_CP¼ 5.0 Hz, CS), 63.21, 63.22 (d, J_CP

¼

37.8 (d, J_CP¼ 4.3 Hz, CH₂, major), 46.3, 48.3 (s, CH₂), 62.2

3

=

7.2 Hz, POCH₂CH₃), 209.0 (d, J_CP¼ 7.4 Hz, C O). IR

(s, COCH₂, major), 62.3 (s, COCH₂, minor), 64.0 (d,

(ﬁlm): n/cm^ꢁ11254 s (P O), 1712 s (C O). MS (CI-isobu-

tane): m/z (%) 295 (100) [M + H]⁺. HRMS (CI) calcd for

C₁₂O₄H₂₃PS + H [M + H]⁺295.1136; found: 295.1135. Yield:

59%. R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.46. Minor iso-

²J_CP¼ 6.8 Hz, POCH₂), 66.6 (s, CS), 164.5 (s, COCH₂),

=

ꢁ1

=

1256 s (P O), 1713 s

200.3 (s, C O). IR (ﬁlm): n/cm

=

(C O), 1736 s (EtC O). MS (CI-isobutane): m/z (%) 353

(100) [M + H]⁺. Anal. calcd for C₁₄H₂₅O₆PS (352.42): C,

47.71; H, 7.16; P, 8.79; S, 9.10; found: C, 47.38; H, 7.26; P,

8.70; S, 8.78%. Yield ¼ 90%. R_f(ethyl acetate–petroleum ether

1:2) ¼ 0.25.

1

3

mer of 9a: H NMR (CDCl₃): d 0.97 (d, J_HH¼ 6.5 Hz, 3H,

3

4

CHCH₃), 1.29 (dt, J_HH¼ 7.0 Hz, J_HP¼ 2.5 Hz, 6H,

OCH₂CH₃), 1.56 (s, 3H, CCH₃), 1.62–1.79 (m, 2H, CH₂),

1.99–2.06 (m, 2H, CH₂), 2.09–2.29 (m, 2H, CH₂), 2.24 (dd,

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-5-phenyl-2-oxocyclo-

hexanecarboxylate (9d). The ratio of diastereoisomers is 5:1.

³J_HH¼ ³J_HH¼ 13.2 Hz, J_HH¼ ³J_HH¼ 5.5 Hz, 2H, CH₂),

3

New J. Chem., 2002, 26, 1753–1767

1759

View Article Online

2

3

Major isomer of 9d: ¹H NMR (500 MHz, CDCl₃): d 1.20–1.45

(m, 9H, OCH₂HC₃), 2.04 (m, 1H, CH₂), 2.08–2.56 (m, 2H,

POCH₂CH₃), 1.48 (dd, J_HH¼ 13.1 Hz, J_HH¼ 3.0 Hz, 1H,

CCH₂CH), 1.80 (dd, ²J_HH¼ ³J_HH¼ 13.1 Hz, 1H, CCH₂CH),

2

CH₂), 2.67–2.81 (m, 2H, CH₂), 3.16 (ddd, J_HH¼ ³J_HH

¼

2.41 [dd, J_HH¼ 14.5 Hz, 1H, CH₂C(O)], 2.64 (m, 1H,

13.9 Hz, ³J_HH¼ 6.2 Hz, 1H, CH₂), 3.66 (dddd,

³J_HH¼ ³J_HH¼ 3.8 Hz, ³J_HH¼ ³J_HH¼ 12.0 Hz, 1H, PhCH),

4.05–4.40 (m, 6H, OCH₂), 7.15–7.42 (m, 5H, CH_arom). ³¹P

NMR (CDCl₃): d 20.8. ¹³C NMR (DEPT, CDCl₃): d 13.8 (s,

CHCH₃), 2.86 [d, J_HH¼ 14.5 Hz, 1H, CH₂C(O)], 4.20 (q,

2

³J_HH¼ 7.1 Hz, 2H, COCH₂CH₃), 4.10–4.36 (m, 4H,

POCH₂CH₃). ³¹P NMR (CDCl₃): d 22.4. ¹³C NMR (DEPT,

3

CDCl₃): d 13.9 (s, COCH₂CH₃), 15.9 (d, J_CP¼ 3.4 Hz,

3

COCH₂CH₃), 15.8, (d, J_CP¼ 7.1 Hz, POCH₂CH₃), 34.2,

POCH₂CH₃), 18.2 (s, CHCH₃), 26.6, 31.9 [s, C(CH₃)₂], 23.4

3

38.1 (s, CH₂), 38.2 (s, CH), 42.9 (d, J_CP¼ 4.6 Hz, CH₂CS),

[s, C(CH₃)₂], 38.4 (d, J_CP¼ 4.9 Hz, CHCH₃), 44.1 (s,

2

62.4 (s, COCH₂), 64.1, 64.3 (d, J_CP¼ 8.0 Hz, POCH₂), 66.7

CCH₂CH), 52.8 [s, CH₂C(O)], 62.5 (s, COCH₂), 63.8, 64.0

¼

2

3

(d, J_CP¼ 3.6 Hz, CS), 126.7, 128.5, 143.0 (s, CH_arom), 168.2

(d, J_CP¼ 5.7 Hz, POCH₂), 75.0 (s, CS), 166.4 (d, J_CP

3

ꢁ1

=

(s, COCH₂CH₃), 201.8 (d, J_CP¼ 9.2 Hz, C O). IR (KBr):

5.3 Hz, COCH₂CH₃), 200.8 (s, C O). IR (ﬁlm): n/cm

n/cm^ꢁ11265 s (P O), 1718 s (C O), 1734 s (EtC O). MS

(CI-isobutane): m/z (%) 415 (100) [M + H]⁺. Anal. calcd for

C₁₉H₂₇O₆PS (414.50): C, 55.06; H, 6.57; P, 7.47; S, 7.74; found:

C, 54.90; H, 6.60; P, 7.48; S, 7.36%. Yield: 72%. R_f(ethyl acet-

ate–petroleum ether 1:2) ¼ 0.24. Minor isomer of 9d: ¹H

NMR (CDCl₃): d 1.3–1.44 (m, 9H, OCH₂CH₃), 2.05–2.17

1251 s (P O), 1715 s (C O), 1738 s (EtC O). MS (CI-iso-

butane): m/z (%) 381 (100) [M + H]⁺. Anal. calcd for

C₁₆H₂₉O₆PS (380.49): C, 50.50; H, 7.70; P, 8.14; S, 8.43; found:

C, 50.36; H, 7.61; P, 8.05; S, 8.22%. Yield: 28%. R_f(ethyl

=

1

acetate–petroleum ether 1:5) ¼ 0.65. Minor isomer of 9f: H

3

NMR (CDCl₃): d 0.92 [s, 3H, C(CH₃)₂], 0.98 (d, J_HH¼ 6.7

(m, 2H, CH₂), 2.38 (dd, J_HH¼ ³J_HH¼ 13.7 Hz, 1H,

Hz, 3H, CHCH₃), 1.04 [s, 3H, C(CH₃)₂], 1.24–1.36 (m, 10H,

2

CH₂CS), 2.65–3.30 (m, 4H, CH₂), 4.10–4.36 (m, 4H, POCH₂),

OCH₂CH₃, CCH₂CH), 1.87 (dd, J_HH¼ ³J_HH¼ 13.3 Hz,

3

2

4.33 (q, J_HH¼ 7.1 Hz, 2H, COCH₂CH₃), 7.12–7.40 (m, 5H,

1H CCH₂CH), 2.03 [dd, J_HH¼ 13.3 Hz, 1H, CH₂C(O)],

CH_arom). ³¹P NMR (CDCl₃): d 22.3. ¹³C NMR (CDCl₃): d

2.93 (m, 1H, CHCH₃), 3.14 [d, J_HH¼ 13.3 Hz, 1H,

2

3

13.8 (s, COCH₂CH₃), 15.8, 15.9 (d, J_CP¼ 7.8 Hz,

CH₂C(O)], 4.05–4.26 (m, 6H, OCH₂CH₃). ³¹P NMR (CDCl₃):

POCH₂CH₃), 33.2, 40.0 (s, CH₂), 40.9 (s, CH), 46.9 (s,

d 21.4. ¹³C NMR (DEPT, CDCl₃): d 14.0 (s, COCH₂CH₃),

2

3

CH₂CS), 62.8 (s, CH₂) 64.2, 64.3 (d, J_CP¼ 7.7 Hz, POCH₂),

15.8, 15.9 (d, J_CP¼ 6.5 Hz, POCH₂CH₃), 17.0 (s, CHCH₃),

2

3

67.1 (d, J_CP¼ 2.3 Hz, CS), 126.6, 128.6, 142.9 (s, CH_arom),

25.9, 31.7 (s, C(CH₃)₂), 35.2 (s, C(CH₃)₂), 37.0 (d, J_CP¼ 9.7

3

167.6 (d, J_CP¼ 5.4 Hz, COCH₂CH₃), 200.4 (d, J_CP¼ 6.5

Hz, CHCH₃), 42.4 (s, CCH₂CH), 49.7 [s, CH₂C(O)], 62.3 (s,

ꢁ1

2

=

Hz, C O). IR (KBr): n/cm 1265 s (P O), 1718 s (C O),

COCH₂CH₃), 64.0, 64.8 (d, J_CP¼ 7.5 Hz, POCH₂), 71.5 (s,

=

CS), 168.5 (s, COCH₂CH₃), 202.3 (s, C O). IR (ﬁlm):

1734 s (EtC O). MS (CI-isobutane): m/z (%) 415 (100)

[M + H]⁺. Anal. calcd for C₁₉H₂₇O₆PS (414.50): C, 55.06; H,

6.57; P, 7.47; S, 7.74; found: C, 55.21; H, 6.59; P, 7.32; S,

7.39%. Yield: 16%. R_f(ethyl acetate–petroleum ether 1:2) ¼

0.27.

n/cm^ꢁ11250 s (P O), 1717 s (C O), 1732 s (EtC O). MS

(CI-isobutane): m/z (%) 381 (100) [M + H]⁺. Anal. calcd for

C₁₆H₂₉O₆PS (380.49): C, 50.50; H, 7.70; P, 8.14; S, 8.43; found:

C, 50.38; H, 7.65; P, 7.95; S, 8.20%. Yield: 24%. R_f(ethyl

acetate–petroleum ether 1:2) ¼ 0.43.

=

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-5-tert-butyl-2-oxocy-

clohexanecarboxylate (9e). The ratio of diastereoisomers is

Ethyl 1-[(dineopentoxyphosphoryl)sulfanyl]-3-methyl-2-oxocy-

clohexanecarboxylate (9g). The ratio of diastereoisomers is

1

2.5:1. Major isomer of 9e: H NMR (CDCl₃): d 0.93 (s, 9H,

1

C(CH₃)₃), 1.26–1.36 (m, 9H, OCH₂CH₃), 1.55 (m, 1H, CH),

2.00–2.20 (m, 2H, CH₂), 2.32–2.71 (m, 3H, CH₂), 2.90 (m,

1H, CH₂), 4.10–4.30 (m, 6H, OCH₂CH₃). ³¹P NMR (CDCl₃):

d 20.9. ¹³C NMR (DEPT, CDCl₃): d 13.8 (s, COCH₂CH₃),

3.8:1. Major isomer of 9g: H NMR (CDCl₃): d 0.91 (s, 9H,

3

CCH₃), 0.92 (s, 9H, CCH₃), 0.98 (d, J_HH¼ 6.3 Hz, 3H,

3

CHCH₃), 1.28 (t, J_HH¼ 6.3 Hz, OCH₂CH₃), 1.40 (m, 1H,

CH₂), 1.77 (m, 1H, CH₂), 2.08 (m, 1H, CH₂), 2.22 (m, 1H,

3

15.8 (d, J_CP¼ 6.9 Hz, POCH₂CH₃), 27.4 (s, CCH₃), 28.0 (s,

CH₂), 2.45–2.63 (m, 2H, CH₂), 3.09 (ddq, J_HH¼ 18.5 Hz,

3

CH₂), 32.2 [s, C(CH₃)₃], 37.7 (d, J_CP¼ 5.1 Hz, CH₂), 37.9

³J_HP¼ 6.3 Hz, J_HH¼ 1.2 Hz, CHCH₃), 3.65–3.87 9 (m,

(s, CH₂), 41.7 [s, CHC(CH₃)₃], 62.3 (s, COCH₂CH₃), 64.1,

4H, OCH₂C), 4.15–4.37 (m, 2H, OCH₂CH₃). ³¹P NMR

(CDCl₃): d 21.0. ¹³C NMR (CDCl₃): d 13.9 (s, CHCH₃),

14.7 (s, OCH₂CH₃), 20.8 (s, CH₂), 25.9 (s, CCH₃), 31.9 (d,

2

64.3 (d, J_CP¼ 7.4 Hz, POCH₂), 66.8 (d, J_CP¼ 3.4 Hz,

3

=

CS), 168.7 (s, COCH₂CH₃), 202.8 (d, J_CP¼ 8.8 Hz, C O).

IR (ﬁlm): n/cm^ꢁ11249 s (P O), 1721 s (C O), 1736 s

³J_CP¼ 7.2 Hz, CCH₃), 36.4 (s, CH₂), 37.1 (d, J_CP¼ 3.3 Hz,

3

=

+

(EtC O). MS (CI-isobutane): m/z (%) 395 (100) [M + H] ,

2

=

CH₂), 41.9 (s, CH), 62.2 (s, COCH₂CH₃), 67.3 (d, J_CP¼ 3.5

349 (18). HRMS (CI) [M + H]⁺found: 395.1649; C₁₇H₃₂O₆PS

requires 395.1657. Yield: 47%. R_f(ethyl acetate–petroleum

Hz, CS), 76.9, 77.0 (d, J_CP¼ 7.1 Hz, POCH₂), 168.7 (s,

2

3

ꢁ1

=

COCH₂), 204.8 (d, J_CP¼ 10.3 Hz, C O). IR (ﬁlm): n/cm

= =

1

ether 1:1) ¼ 0.48. Minor isomer of 9e: H NMR (CDCl₃): d

1266 s (P O), 1732 s (C O). MS (CI-isobutane): m/z (%)

437 (100) [M + H]⁺. Anal. calcd for C₂₀H₃₇O₆PS (436.61): C,

55.01; H, 8.56; P, 7.09; S, 7.35; found: C, 54.70; H, 8.48; P,

6.78; S, 7.02%. Yield: 43%. R_f(ethyl acetate–petroleum ether

1:2) ¼ 0.35.

0.95 (s, 9H, C(CH₃)₃), 1.20–1.35 (m, 9H, OCH₂CH₃), 1.42–

2.16 (m, 3H, CH₂), 2.21–3.12 (m, 3H, CH₂), 2.21–3.12 (m,

3H, CH, CH₂), 3.82 (m, 1H, CH₂), 4.11–4.32 (m, 6H,

OCH₂CH₃). ³¹P NMR (CDCl₃): d 22.4. ¹³C NMR (DEPT,

3

CDCl₃): d 13.8 (s, COCH₂CH₃), 15.8 (d, J_CP¼ 6.9 Hz,

POCH₂CH₃), 27.1 (s, CH₂), 27.3 [s, C(CH₃)₃], 32.4 [s,

Reaction of thiophosphates 8 and 9 with sodium borohydride.

General procedure. To a stirred suspension of sodium borohy-

dride (0.076 g, 2 mmol) in dry methanol–dichloromethane (40

mL in the ratio 1:1) was added dropwise at ꢁ78 ^ꢀC under

argon atmosphere to a solution of the appropriate thiopho-

sphate (1 mmol) in dichloromethane (5 mL). The reaction

was monitored by TLC and stirring was continued at ꢁ78 ^ꢀC

until no starting thiophosphate 8 or 9 was detectable (3 h).

The reaction was stopped by addition of 1 mL of dry acetone

and after an additional 30 min ice water was added. The reac-

tion mixture was extracted with dichloromethane (2 ꢃ 10 mL),

washed with NH₄Cl (5 mL) and dried over MgSO₄. Solvent

was removed under reduced pressure and the residue was ana-

3

C(CH₃)₃], 39.9 (s, CH₂), 40.5 (d, J_CP¼ 3.4 Hz, CH₂), 44.7

2

(s, CH), 62.4 (s, COCH₂CH₃), 64.1, 64.3 (d, J_CP¼ 7.4 Hz,

2

3

POCH₂CH₃), 67.2 (d, J_CP¼ 3.5 Hz, CS), 167.8 (s, J_CP

¼

3

=

5.0 Hz, COCH₂CH₃), 201.2 (d, J_CP¼ 5.8 Hz, C O). IR

(ﬁlm): n/cm^ꢁ11251 s (P O), 1720 s (C O), 1739 s (EtC O).

MS (CI-isobutane): m/z (%) 395 (100) [M + H]⁺. HRMS

(CI) calcd for C₁₇H₃₁O₆PS + H [M + H]⁺395.1657; found:

395.1649. Yield: 16%. R_f¼ (ethyl acetate–petroleum ether

1:1) ¼ 0.39.

=

Ethyl 1-[(diethoxyphosphoryl)sulfanyl]-4,4,6-trimethyl-2-oxo-

cyclohexanecarboxylate (9f). The ratio of diastereoisomers is

1

1.2:1. Major isomer of 9f: H NMR (CDCl₃): d 1.02 [s, 6H,

3

1

C(CH₃)₂] 1.24 (d, J_HH¼ 6.8 Hz, 3H, CHCH₃), 1.28 (t,

lyzed by ³¹P and H NMR spectroscopy (see Tables 3 and 4).

The crude reaction mixture was subjected to silica gel column

³J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.28–1.40 (m, 6H,

1760

New J. Chem., 2002, 26, 1753–1767

View Article Online

chromatography with a gradient of petroleum ether–ethyl

acetate (20:1 to 5:1) to provide the pure thiols (colourless oils)

14 and 18, episulﬁdes (colourless oils) 15 and 19 and oleﬁns

(colourless liquids) 16 and 20.

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-sulfanylcyclopentanecar-

boxylate (14a). Single diastereoisomer.¹H NMR (CDCl₃): d

Ethyl 2-[(diethoxyphosphoryl)oxy]-4-methyl-1-sulfanylcyclo-

hexanecarboxylate (18c). Single diastereoisomer.¹H NMR

3

(CDCl₃): d 0.93 (d, J_HH¼ 5.9 Hz, 3H, CHCH₃), 1.27 (t,

3

³J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.29 (dt, J_HH¼ 7.1 Hz,

⁴J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.44–1.60 (m, 4H, CH₂),

1.74–2.15 (m, 3H, CH₂), 2.34 (s, 1H, SH), 4.00–4.12 (m, 4H,

3

1.25 (t, J_HH¼ 7.2 Hz, 3H, COCH₂CH₃), 1.33 (t, J_HH

¼

POCH₂), 4.12–4.20 (m, 2H, COCH₂), 4.79 (ddd, J_HH¼ 11.3

3

7.1 Hz, 6H, POCH₂CH₃), 1.38–2.21 (m, 5H, CH₂), 2.37 (m,

1H, CH₂), 2.43 (s, 1H, SH), 4.05–4.24 (m, 4H, POCH₂), 4.18

Hz, J_HP¼ 6.4 Hz, J_HH¼ 4.5 Hz, 1H, CHOP). ³¹P NMR

(CDCl₃): d ꢁ2.2. ¹³C NMR (CDCl₃): d 13.9 (s, COCH₂CH₃),

16.0 (d, ³J_CP¼ 6.8 Hz, POCH₂CH₃), 21.5 (s, CHCH₃), 28.9 (s,

CH₂), 30.9 (s, CHCH₃), 35.5, 36.9 (s, CH₂), 57.8 (d, ³J_CP¼ 8.2

3

(q, J_HH¼ 7.1 Hz, 2H, COCH₂), 4.97 (ddd, J_HP

¼

³J_HH¼ ³J_HH¼ 6.5 Hz, 1H, CHOP). ³¹P NMR (CDCl₃): d

ꢁ1.8. ¹³C NMR (CDCl₃): d 13.8 (s, COCH₂CH₃), 15.9 (d,

³J_CP¼ 6.3 Hz, POCH₂CH₃), 19.4, 30.1, 35.3 (s, CH₂), 57.6

2

Hz, CS), 62.2 (s, COCH₂), 63.7, 63.8 (d, J_CP¼ 6.8 Hz,

2

=

POCH₂), 78.7 (d, J_CP¼ 5.4 Hz, CHOP), 172.7 (s, C O).

3

IR (ﬁlm): n/cm^ꢁ11264 s (P O), 1732 s (C O). MS (CI-iso-

butane): m/z (%) 355 (100) [M + H]⁺, 155 (8)

[H + HOP(O)(OEt)₂]⁺. Anal. calcd for C₁₄H₂₇O₆PS (354.45):

C, 47.45; H, 7.68; P, 8.74; S, 9.05; found: C, 46.90; H, 7.65;

P, 8.52; S, 8.66%. Yield: 83%. R_f(ethyl acetate) ¼ 0.48.

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-phenyl-1-sulfanylcyclo-

hexanecarboxylate (18d). Single diastereoisomer.¹H NMR

(CDCl₃): d 1.20–1.33 (m, 9H, OCH₂CH₃), 1.66 (m, 1H,

CH₂), 1.87 (m, 1H, CH), 2.08–2.25 (m, 4H, CH₂), 2.56 (s,

1H, SH), 3.05 (m, 1H, CH₂), 4.05–4.27 (m, 6H, OCH₂), 4.92

=

(d, J_CP¼ 8.6 Hz, CS), 61.7 (s, COCH₂), 63.7, 63.8 (d,

²J_CP¼ 6.2 Hz, POCH₂), 81.4 (d_ꢁ, ₁J_CP¼ 4.8 Hz, CHOP),

2

=

1266 s (P O), 1730 s

172.3 (s, C O). IR (ﬁlm): n/cm

+

=

(C O). MS (EI, 70 eV): m/z (%) 326 (3) [M] , 155 (100),

127 (35), 99 (44). Anal. calcd for C₁₂H₂₃O₆PS (326.39): C,

44.16; H, 7.10; P, 9.49; S, 9.82; found: C, 43.93; H, 7.10; P,

9.14; S, 9.38%. Yield: 85%. R_f(ethyl acetate) ¼ 0.42.

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-sulfanylcyclohexanecar-

1

boxylate (14b). Single diastereoisomer. H NMR (CDCl₃): d

3

4

1.33 (dt, J_HH¼ 7.2 Hz, J_HP¼ 1 Hz, 6H, POCH₂CH₃),

3

1.30 (t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.55–1.78 (m, 4H,

(ddd, J_HH¼ 12.1 Hz, J_HP¼ 7.7 Hz, J_HH¼ 4.9 Hz, 1H,

CH₂), 1.80–2.00 (m, 2H, CH₂), 2.00–2.16 (m, 2H, CH₂), 2.42

CHOP). ³¹P NMR (CDCl₃): d ꢁ1.9. ¹³C NMR (DEPT,

3

(s, 1H, SH), 4.12 (q, J_HH¼ 7.1 Hz, 2H, COCH₂), 4.18 (m,

CDCl₃): d 13.8 (s, COCH₂CH₃), 15.8 (d, J_CP¼ 6.8 Hz,

3

4H, POCH₂), 4.84 (ddd, J_HP¼ 14.6 Hz, J_HH¼ 7.5 Hz,

³J_HH¼ 3.0 Hz, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ1.8. ¹³C

NMR (DEPT, CDCl₃): d 13.8 (s, COCH₂CH₃), 16.0 (d,

³J_CP¼ 6.7 Hz, POCH₂CH₃), 20.9, 21.9, 29.0, 33.9 (s, CH₂),

POCH₂CH₃), 28.8, 31.0 (s, CH₂), 37.9 (s, CH), 42.9 (s, CH₂),

3

58.2 (d, J_CP¼ 8.6 Hz, CS), 62.2 (s, COCH₂), 63.5, 63.6 (d,

²J_CP¼ 5.2 Hz, POCH₂), 78.2 (d, J_CP¼ 4.6 Hz, CHOP),

2

=

126.6, 128.4, 143.8 (s, CH_arom) 171.9 (s, C O). IR (ﬁlm):

3

n/cm^ꢁ11250 s (P O), 1729(C O). MS (EI, 70 eV): m/z 416

(3) [M]⁺, 155 (100), 127 (60), 104 (99), 91 (56). Anal. calcd

for C₁₉H₂₉O₆PS (416.52): C, 54.78; H, 7.03; P, 7.43; S, 7.70;

found: C, 54.58; H, 6.81; P, 7.29; S, 7.32%. Yield: 85%. R_f

(ethyl acetate–petroleum ether 1:1) ¼ 0.10.

=

55.6 (d, J_CP¼ 8.6 Hz, CS), 61.8 (s, COCH₂), 63.6, 63.8 (d,

²J_CP¼ 6.0 Hz, POCH₂), 77.8 (d_ꢁ, ₁J_CP¼ 4.5 Hz, CHOP),

2

=

1264 s (P O), 1729 s

172.1 (s, C O). IR (ﬁlm): n/cm

+

=

(C O). MS (CI-isobutane): m/z (%) 341 (100) [M + H] , 155

(7) [H + HOP(O)(OEt)₂]⁺. Anal. calcd for C₁₃H₂₅O₆PS

(340.42): C, 45.87; H, 7.40; P, 9.10; S, 9.42; found: C, 45.30;

H, 6.67; P, 8.78; S, 8.92%. Yield:89%. R_f(ethyl acetate) ¼

0.42.

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-tert-butyl-1-sulfanylcy-

clohexanecarboxylate (18e). Single diastereoisomer.¹H NMR

(CDCl₃): d 0.85 (s, 9H, CCH₃), 1.10–1.32 (m, 9H, OCH₂CH₃),

1.42–2.30 (m, 7H, CH₂), 2.44 (s, 1H, SH), 4.00–4.20 (m, 6H,

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-sulfanylcycloheptanecar-

boxylate (14c). Single diastereoisomer.¹H NMR (CDCl₃): d

3

OCH₂), 4.76 (ddd, J_HH¼ 11.5 Hz, J_HP¼ 6.3 Hz,

3

1.28 (t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.30 (dt,³J_HH

¼

³J_HH¼ 4.7 Hz, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ2.1. ¹³C

4

3

7.1 Hz, J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.35–2.32 (m, 10H,

NMR (CDCl₃): d 13.9 (s, COCH₂CH₃), 15.9 (d, J_CP¼ 6.3

CH₂), 2.50 (s, 1H, SH), 4.05–4.28 (m, 6H, OCH₂), 4.94 (ddd,

Hz, POCH₂CH₃), 24.8 (s, CH₂), 27.2 [s, C(CH₃)₃], 28.7 (s,

CH₂), 31.9 [s, C(CH₃)₃], 37.1 (s, CH₂), 41.5 [s, CHC(CH₃)₃],

³J_HP¼ ³J_HH¼ 8.1 Hz, J_HH¼ 2.5 Hz, 1H, CHOP). ³¹P

3

NMR (CDCl₃): d ꢁ1.9. ¹³C NMR (CDCl₃): d 13.8 (s,

58.5 (d, J_CP¼ 8.4 Hz, CS), 62.2 (s, COCH₂), 63.5, 63.6 (d,

3

2

COCH₂CH₃), 15.9 (d, J_CP¼ 6.9 Hz, POCH₂CH₃), 22.2,

²J_CP¼ 4.6 Hz, POCH₂), 78.9 (d_ꢁ, ₁J_CP¼ 4.4 Hz, CHOP),

3

=

1252 s (P O), 1731 s

23.0, 26.7, 31.3, 35.0 (s, CH₂), 58.9 (d, J_CP¼ 8.7 Hz, CS),

172.6 (s, C O). IR (ﬁlm): n/cm

2

+

=

61.8 (s, COCH₂), 63.5, 63.7 (d, J_CP¼ 6.9 Hz, POCH₂), 81.7

(C O). MS (CI-isobutane): m/z (%) 397 (100) [M + H] , 155

(20) [H + HOP(O)(OEt)₂]⁺. Anal. calcd for C₁₇H₃₃O₆PS

(396.54): C, 51.49; H, 8.41; P, 7.81; S, 8.07; found: C, 51.03;

H, 8.30; P, 7.14; S, 7.63%. Yield: 71%. R_f(ethyl acetate) ¼

0.30.

2

=

(d, J_CP¼ 5.0 Hz, CHOP), 172.6 (s, C O) ppm. IR (ﬁlm):

n/cm^ꢁ11264 s (P O), 1729 s (C O). MS (CI-isobutane):

m/z (%) 355 (100) [M + H]⁺, 155 (10) [H + HOP(O)(OEt)₂]⁺.

Anal. calcd for C₁₄H₂₇O₆PS (354.45): C, 47.46; H, 7.68; P,

8.74; S, 9.05; found: C, 47.62; H, 7.81; P, 8.43; S, 8.93%. Yield:

49%. R_f(ethyl acetate–petroleum ether 1:5) ¼ 0.12.

=

Ethyl 7-thiabicyclo[4.1.0]heptane-1-carboxylate (15b). Single

3

diastereoisomer. ¹H NMR (CDCl₃): d 1.26 (t, J_HH¼ 7.1

Ethyl 2-[(diethoxyphosphoryl)oxy]-3-methyl-1-sulfanylcyclo-

hexanecarboxylate (18b). Single diastereoisomer. ¹H NMR

Hz, 3H, OCH₂CH₃), 1.29–2.20 (m, 8H, CH₂), 3.75 (dd,

³J_HH¼ 5.1 Hz, ³J_HH¼ 2.4 Hz, 1H, CHS), 4.15 (q, ³J_HH¼ 7.1

7.1 Hz, 2H, OCH₂). ¹³C NMR (CDCl₃): d 14.3 (s, OCH₂CH₃),

3

(CDCl₃): d 1.00 (d, J_HH¼ 6.6 Hz, 3H, CHCH₃), 1.23 (m,

9H, OCH₂CH₃), 1.42–2.35 (m, 7H, CH and CH₂), 2.43 (s,

21.4, 23.7, 25.7, 31.6 (s, CH₂), 41.3 [s, CC(O)OEt], 60.1 (s,

3

ꢁ1

=

1H, SH), 4.00–4.30 (m, 4H, POCH₂), 4.14 (q, J_HH¼ 7.1

OCH₂), 63.5 (s, CHS), 171.5 (s, C O). IR (ﬁlm): n/cm

3

=

Hz, 2H, COCH₂), 4.51 (dd, J_HP¼ 8.9 Hz, J_HH¼ 9.9 Hz,

1745

s

(C O). MS (CI-isobutane): m/z (%) 187 (30)

1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ2.1. ¹³C NMR (CDCl₃):

[M + H]⁺, 145 (100), 83 (43). Anal. calcd for C₉H₁₄O₂S

(186.27): C, 58.03, H, 7.58, S, 17.21; found: C, 57.80, H,

7.57, S, 16.98%. Yield: 10%. R_f(ethyl acetate–petroleum ether

1:2) ¼ 0.67.

3

d 13.5 (s, COCH₂CH₃), 15.6 (d, J_CP¼ 6.6 Hz, POCH₂CH₃),

18.0 (s, CHCH₃), 20.5, 31.8, 33.7 (s, CH₂), 36.5 (s, CHCH₃),

2

59.2 (s, CS), 62.0 (s, COCH₂), 63.2, 63.4 (d, J_CP¼ 6.7 Hz,

2

=

POCH₂), 84.2 (d, J_CP¼ 5.0 Hz, CHOP), 172.0 (s, C O).

Ethyl 8-thiabicyclo[5.1.0]octane-1-carboxylate (15c). Single

IR (ﬁlm): n/cm^ꢁ11268 s (P O), 1731 s (C O). MS (CI-iso-

butane): m/z (%) 355 (100) [M + H]⁺, 155 (12)

[H + HOP(O)(OEt)₂]⁺. Anal. calcd for C₁₄H₂₇O₆PS (354.45):

C, 47.45; H, 7.68; P, 8.74; S, 9.05; found: C, 46.90; H, 7.51;

P, 8.41; S, 8.48%. Yield: 90%. R_f(ethyl acetate) ¼ 0.50.

diastereoisomer. ¹H NMR (CDCl₃): d 1.26 (t, J_HH¼ 7.1

3

=

Hz, 3H, OCH₂CH₃), 1.29–1.95 (m, 8H, CH₂), 2.54 (m, 1H,

¼

3

CH₂), 2.90 (m, 1H, CH₂), 3.63 (dd, J_HH¼ 9.2 Hz, J_HH

3

5.3 Hz, 1H, CHS), 4.17 (q, J_HH¼ 7.1 Hz, 2H, OCH₂). ¹³C

NMR (CDCl₃): d 13.8 (s, OCH₂CH₃), 26.3, 26.5, 30.9, 32.2,

New J. Chem., 2002, 26, 1753–1767

1761

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32.5 (s, CH₂), 43.9 (s, CHS), 47.6 [s, CC(O)OEt], 61.5 (s,

(19.9) [M]⁺, 139 (10). [M⁺ꢁC₂H₅], 123 (26), 122 (22), 95

(100), 94 (40).%. Yield: 25%. R_f(ethyl acetate–petroleum ether

1:1) ¼ 0.75.

ꢁ1

=

OCH₂), 171.8 (s, C O). IR (ﬁlm): n/cm 1727 s (C O).

MS (CI-isobutane): m/z (%) 187 (100) [M + H]⁺. Anal. calcd

for C₁₀H₁₆O₂S (200.30): C, 59.96, H, 8.05, S, 16.01; found:

C, 59.62, H, 8.09, S, 15.63%. Yield: 24%. R_f(ethyl acetate–

petroleum ether 1:5) ¼ 0.60.

1

4-Methylcyclohex-1-enecarboxylic acid ethyl ester (20c)³². H

3

NMR (CDCl₃): d 0.97 (d, J_HH¼ 6.4 Hz, 3H, CHCH₃), 1.27

3

(t, J_HH¼ 7.1 Hz, 3H, OCH₂CH₃), 1.56 (dd, J_HH¼ 3.3, 6.5

3

Hz, 1H, CH₂), 1.59–1.68 (m, 2H, CH₂), 2.05 (dd, J_HH

Ethyl5-methyl-7-thiabicyclo[4.1.0]heptane-1-carboxylate(19b).

¼

1

3

Single diastereoisomer. H NMR (CDCl₃): d 1.12 (d, J_HH

¼

1.8, 6.4 Hz, 1H, CH₂), 2.31 (ddq, J_HH¼ 2.2, 6.5, 8.4 Hz,

6.5 Hz, 3H, CHCH₃), 1.26 (t, ³J_HH¼ 7.1 Hz, 3H, OCH₂CH₃),

1H, CHCH₃), 2.41–2.48 (m, 1H, CH₂), 2.60 (dd, J_HH¼ 2.4,

3

1.47–1.70 (m, 4H, CH₂), 2.14–2.19 (m, 3H, CH₂), 2.59 (dtq,

6.0 Hz, 1H, CH₂), 4.17 (q, J_HH¼ 7.1 Hz, 2H, OCH₂), 6.9

³J_HH¼ 4.0, 5.0, 6.9 Hz, 1H, CHCH₃), 3.82 (d, J_HH¼ 3.8

(dd, J_HH¼ 1.3, 3.6. Hz, 1H, C CH). Yield: 20%. R_f(ethyl

3

=

3

Hz, 1H, CHS), 4.17 (q, J_HH¼ 7.1 Hz, 2H, OCH₂). IR (ﬁlm):

acetate–petroleum ether 1:1) ¼ 0.7.

n/cm^ꢁ11734 s (C O), 795 s. MS (EI, 70 eV): m/z (%) 200

5-Phenylcyclohex-1-enecarboxylic acid ethyl ester (20d). ¹H

=

(19) [M]⁺, 167 (15), [M⁺ꢁSH], 93 (100). HRMS found

200.0874; C₁₀H₁₆O₂S requires 200.0871. Yield: 60%. R_f(ethyl

acetate–petroleum ether 1:2) ¼ 0.7.

NMR (CDCl₃): d 1.28 (t, J_HH¼ 7.1 Hz, 3H, OCH₂CH₃),

3

1.77 (dd, J_HH¼ 8.8, 12.2 Hz, 1H, CH₂), 1.93–2.05 (m, 1H,

3

CH₂), 2.32–2.43 (m, 2H, CH₂), 2.71 (dd, J_HH¼ 3.0, 8.9 Hz,

3

Ethyl4-methyl-7-thiabicyclo[4.1.0]heptane-1-carboxylate(19c).

1H, CHC₆H₅), 2.77 (10 lines, 2H, CH₂), 4.20 (q, J_HH¼ 7.1

1

3

=

Single diastereoisomer. H NMR (CDCl₃): d 0.88 (d, J_HH

¼

Hz, 2H, OCH₂), 7.06 (dd, J_HH¼ 2.0, 4.0. Hz, 1H, C CH),

6.3 Hz, 3H, CHCH₃), 1.25 (t, ³J_HH¼ 7.1 Hz, 3H, OCH₂CH₃),

7.15–7.58 (m, 5H, CH_arom). MS (EI, 70 eV): m/z (%) 230

(68) [M]⁺, 185 (13), [M⁺ꢁOC₂H₅], 156 (17), 104 (100), 77

(11) [C₆H₅]. HRMS found 230.1309; C₁₅H₁₈O₂S requires

230.1307. Yield: 60%. R_f(ethyl acetate–petroleum ether

1:1) ¼ 0.71

3

1.72 (dd, J_HH¼ 3.5, 8.5 Hz, 2H, CH₂), 2.30 (ddq, J_HH

¼

3

3.0, 6.6, 11.2 Hz, 1H, CHCH₃), 2.32 (td, J_HH¼ 2.0, 8.2 Hz,

3

2H, CH₂), 2.68 (dd, J_HH¼ 3.3, 6.8 Hz, 1H, CH₂), 2.76 (dd,

³J_HH¼ 3.2, 6.7 Hz, 1H, CH₂), 3.88 (dd, J_HH¼ 1.8, 3.4 Hz,

3

1H, CHS), 4.15 (q, J_HH¼ 7.1 Hz, 2H, OCH₂). IR (ﬁlm):

5-tert-Butylcyclohex-1-enecarboxylic acid ethyl ester (20e)³³.

¹H NMR (CDCl₃): d 0.91 [s, 9H, C(CH₃)₃], 1.07 (dd,

³J_HH¼ 5.7, 10.8 Hz, 1H, CH₂), 1.13–1.23 (m, 1H, CH₂) 1.29

n/cm^ꢁ11721 s (C O). MS (EI, 70 eV): m/z (%) 200 (3)

=

[M]⁺, 168 (15), [M⁺ꢁS], 95 (100) [M⁺ꢁSꢁCOOC₂H₅]. Yield:

3

15%. R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.68.

(t, J_HH¼ 7.1 Hz, 3H, OCH₂CH₃), 1.79–1.95 (m, 3H, CH₂),

Ethyl3-phenyl-7-thiabicyclo[4.1.0]heptane-1-carboxylate(19d).

¼

2.18–2.29 and 2.37–2.39 [m, 3H, CH₂and CHC(CH₃)₃CH₂],

1

3

Single diastereoisomer. H NMR (CDCl₃): d 1.31 (t, J_HH

7.1 Hz, 3H, OCH₂CH₃), 1.45–2.95 (m, 7H, CH, CH₂), 3.97

4.19 (q, J_HH¼ 7.1 Hz, 2H, OCH₂), 6.97 (dd, J_HH¼ 1.4,

=

2.8 Hz, 1H, C CH). MS (EI, 70 eV): m/z (%) 210 (22)

3

(dd, J_HH¼ 3.7 Hz, J_HH¼ 1.5 Hz, 1H, CHS), 4.20 (q,

³J_HH¼ 7.1 Hz, 2H, OCH₂), 7.15–7.58 (m, 5H, CH_arom). ¹³C

NMR (CDCl₃): d 14.3 (s, OCH₂CH₃), 28.2, 30.3, 32.1 (s,

[M]⁺, 165 (14), 154 (60) [M⁺ꢁC₄H₈], 153 (30) [M⁺ꢁC₄H₉],

57 (100) [C₄H₉]. Yield: 25%. R_f(ethyl acetate–petroleum ether

1:1) ¼ 0.78.

CH₂), 60.3 (s, COCH₂), 63.6 [s, CC(O)OEt], 72.8 (s, CHS),

ꢁ1

=

170.2 (s, C O). IR (ﬁlm): n/cm 1740 s (C O). MS (CI-iso-

butane): m/z (%) 263 (16) [M + H]⁺, 247 (75), 231 (100). Anal.

calcd for C₁₅H₁₈O₂S (262.37): C, 68.67, H, 6.92, S, 12.22; found:

C, 6835, H, 6.90, S, 11.83%. Yield: 15%.R_f(ethyl acetate–

petroleum ether 1:2) ¼ 0.68.

Reaction of thiophosphates 8 and 9 with sodium borohydride

in the presence of methyl iodide. General procedure. To a sus-

pension of sodium borohydride (0.076 g, 2 mmol) in dry

methanol–dichloromethane (40 mL in the ratio 1:1) was added

a solution of the appropriate thiophosphate 8 or 9 (1 mmol) in

dichloromethane as described above, followed by addition of

methyl iodide (0.71 g, 5 mmol). Stirring was continued at

ꢁ78 ^ꢀC for 3 h and the reaction mixture was allowed to warm

slowly to room temperature. The reaction was monitored by

TLC and stopped after 5–7 h by addition of dry acetone (1

mL) and ice water. The reaction mixture was diluted with

dichloromethane (20 mL), washed with NH₄Cl (5 mL) and

water (5 mL), then dried (MgSO₄). Solvent was removed under

vacuum and the residue was analyzed by ³¹P and ¹H NMR

spectroscopy (see Tables 3 and 4). Crude sulﬁdes 17 and 21

were puriﬁed by column chromatography with a gradient of

petroleum ether–ethyl acetate (20:1 to 5:1), and were obtained

as colourless oils.

Ethyl

3-tert-butyl-7-thiabicyclo[4.1.0]heptane-1-carboxylate

(19e). Single diastereoisomer. ¹H NMR (CDCl₃): d 0.83 [s,

3

9H, C(CH₃)₃], 1.24 (t, J_HH¼ 7.0 Hz, 3H, OCH₂CH₃), 0.95–

3

2.42 (m, 6H, CH, CH₂), 3.86 (dd, J_HH¼ 3.7 Hz, J_HH

¼

1.6 Hz, 1H, CHS), 4.15 (q, J_HH¼ 7.0 Hz, 2H, OCH₂). ¹³C

NMR (CDCl₃): d 14.3 (s, OCH₂CH₃), 21.5, 23.7 (s, CH₂),

27.2 [s, C(CH₃)₃], 30.6 (s, CH₂), 47.7 [s, CHC(CH₃)₃], 60.1

3

(s, OCH₂), 63.5 [s, CC(O)OEt], 73.4 (s, CHS), 169.0 (s,

ꢁ1

=

C O). IR (ﬁlm): n/cm 1741 s (C O). MS (CI-isobutane):

m/z (%) 243 (5) [M + H]⁺, 227 (100), 211 (55) [C₁₃H₂₂O₂].

Anal. calcd for C₁₃H₂₂O₂S (242.38): C, 64.42, H, 9.15, S,

13.23; found: C, 64.02, H, 8,87, S, 12.71%. Yield: 25%. R_f

(ethyl acetate–petroleum ether 1:1) ¼ 0.75.

Cyclohex-1-enecarboxylic acid ethyl ester (16b)²⁹. ¹H NMR

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulfanyl)cyclo-

pentanecarboxylate (17a). Single diastereoisomer. ¹H NMR

3

(CDCl₃): d 1.36 (t, J_HH¼ 7.0 Hz, 3H, OCH₂CH₃), 1.54–

3

1.69 (m, 4H, CH₂), 1.97–2.08 (m, 2H, CH₂), 2.11–2.32 (m,

(CDCl₃): d 1.25 (t, J_HH¼ 7.2 Hz, 3H, COCH₂CH₃), 1.34

3

4

2H, CH₂), 4.26 (q, J_HH¼ 7.0 Hz, 2H, OCH₂), 6.92 (dd,

(dt, J_HH¼ 7.1 Hz, J_HP¼ 1.1 Hz, 6H, POCH₂CH₃), 1.48–

2.25 (m, 7H, CH₂), 2.14 (s, 3H, SCH₃), 2.41 (m, 1H, CH₂),

4.00–4.30 (m, 6H, OCH₂), 5.13 (m, 1H, CHOP). ³¹P NMR

(CDCl₃): d ꢁ1.6. ¹³C NMR (CDCl₃): d 13.0 (s, COCH₂CH₃),

3

=

J_HH¼ 3.6 Hz, J_HH¼ 1.9 Hz, 1H, CH C). Yield: 11%. R_f

(ethyl acetate–petroleum ether 1:1) ¼ 0.7.

Cyclohept-1-enecarboxylic acid ethyl ester (16c)³⁰. ¹H NMR

3

(CDCl₃): d 1.27 (t, J_HH¼ 7.1 Hz, 3H, OCH₂CH₃), 1.47–

13.7 (s, SCH₃), 15.7 (d, J_CP¼ 6.8 Hz, POCH₂CH₃), 19.7,

2

3

2.02 (m, 8H, CH₂), 2.25, 2.29 (AB, J_HH¼ 6.6 Hz, 2H,

30.7, 32.1 (s, CH₂), 60.7 (d, J_CP¼ 8.4 Hz, CS), 61.1 (s,

3

2

CH₂), 4.15 (q, J_HH¼ 7.1 Hz, 2H, OCH₂), 7.15 (t, J_HH

¼

COCH₂), 63.3, 63.5 (d, J_CP¼ 6.9 Hz, POCH₂), 80.5 (_ꢁd₁,

2

=

6.7 Hz, 1H, CH C). Yield: 31%. R_f(ethyl acetate–petroleum

ether 1:1) ¼ 0.63.

J_CP¼ 4.9 Hz, CHOP), 170.8 (s, C O). IR (ﬁlm): n/cm

=

1263 s (P O), 1722 s (C O). MS (CI-isobutane): m/z (%)

341 (100) [M]⁺, 187 (10). Anal. calcd for C₁₃H₂₅O₆PS

(340.42): C, 45.88; H, 7.40; P, 9.10; S, 9.42; found: C, 45.86;

H, 7.42; P, 9.01; S, 9.21%. Yield: 82%. R_f(ethyl acet-

ate) ¼ 0.45.

3-Methylcyclohex-1-enecarboxylic acid ethyl ester (20b)³¹. H

1

3

NMR (CDCl₃): d 1.04 (d, J_HH¼ 7.0 Hz, 3H, CHCH₃), 1.28

3

(t, J_HH¼ 7.1 Hz, 3H, OCH₂CH₃), 1.73–1.82 (m, 3H, CH₂),

3

2.21–2.29 (m, 4H, CH₂), 2.53 (dtq, J_HH¼ 1.8, 5.9, 6.9 Hz,

3

1H, CHCH₃), 4.16 (q, J_HH¼ 7.1 Hz, 2H, OCH₂), 6.8 (d,

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulfanyl)cyclo-

hexanecarboxylate (17b). Single diastereoisomer. ¹H NMR

3

=

J_HH¼ 1.8 Hz, 1H, CH C). MS (EI, 70 eV): m/z (%) 168

1762

New J. Chem., 2002, 26, 1753–1767

View Article Online

3

(CDCl₃): d 1.28 (t,³J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.33

SCH₃), 2.25–2.35 (m, 2H, CH₂), 2.94 (dddd, J_HH¼ 3.3 Hz,

³J_HH¼ 12.4 Hz, 1H, CHPh), 4.05–4.30 (m, 6H, OCH₂), 5.13

(m, 1H, CHOP), 7.10–7.45 (m, 5H, CH_arom). ³¹P NMR

(CDCl₃): d ꢁ2.1. ¹³C NMR (DEPT, CDCl₃): d 12.6 (s,

4

(dt,³J_HH¼ 7.2 Hz, J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 0.88–

1.80 (m, 6H, CH₂), 2.08 (s, 3H, SCH₃), 2.10–2.16 (m, 2H,

3

CH₂), 4.05–4.23 (m, 4H, POCH₂), 4.21 (q, J_HH¼ 7.1 Hz,

3

2H, COCH₂), 4.93 (ddd, J_HH¼ ³J_HP¼ 5.2 Hz, J_HH¼ 6.5

Hz, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ1.7. ¹³C NMR

(CDCl₃): d 11.5 (s, SCH₃), 14.0 (s, COCH₂CH₃), 15.9 (d,

³J_CP¼ 6.8 Hz, POCH₂CH₃), 18.9, 22.7, 28.6, 29.0 (s, CH₂),

SCH₃), 13.8 (s, COCH₂CH₃), 15.8 (d, J_CP¼ 6.8 Hz,

POCH₂CH₃), 28.7, 30.9 (s, CH₂), 37.4 (s, CH), 40.0 (s, CH₂),

3

58.1 (d, J_CP¼ 8.6 Hz, CS), 62.3 (s, COCH₂), 63.1, 63.2 (d,

²J_CP¼ 6.8 Hz, POCH₂), 79.5 (d, J_CP¼ 5.1 Hz, CHOP),

2

3

=

55.3 (d, J_CP¼ 8.5 Hz, CS), 61.0 (s, COCH₂), 63.5, 63.7 (d,

126.3, 126.4, 128.2, 143.9 (s, CH_arom), 171.2 (s, C O). IR

²J_CP¼ 6.0 Hz, POCH₂), 73.7 (d_ꢁ, ₁J_CP¼ 4.0 Hz, CHOP),

(ﬁlm): n/cm^ꢁ11272 s (P O), 1719 s (C O). MS ( CI-iso-

butane): m/z (%) 431 (100) [M + H]⁺. Anal. calcd for

C₂₀H₃₁O₆PS (430.55): C, 55.79; H, 7.27; P, 7.19; S, 7.45;

found: C, 55.40; H, 7.19; P, 6.88; S, 7.02%. Yield: 60%. R_f

(ethyl acetate–petroleum ether 1:2) ¼ 0.12.

2

=

1259 s (P O), 1714 s

170.1 (s, C O). IR (ﬁlm): n/cm

+

=

(C O). MS (CI-isobutane): m/z (%) 355 (100) [M + H] , 201

(12). Anal. calcd for C₁₄H₂₇O₆PS (354.45): C, 47.45; H, 7.68;

P, 8.74; S, 9.05; found: C, 47.45; H, 7.68; P, 8.50; S, 8.48%.

Yield: 79%. R_f(ethyl acetate–petroleum ether 1:2) ¼ 0.49.

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulfanyl)cyclo-

heptanecarboxylate (17c). Single diastereoisomer. ¹H NMR

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-tert-butyl-1-(methylsul-

fanyl)cyclohexanecarboxylate (21e). Single diastereoi-

somer.¹H NMR (CDCl₃): d 0.85 (s, 9H, CCH₃), 1.20–1.45

(m, 9H, OCH₂CH₃), 1.40–1.70 (m, 4H, CH₂), 1.83 (m, 1H,

CH₂), 2.08–2.20 (m, 2H, CH, CH₂), 2.17 (s, 3H, SCH₃),

4.00–4.50 (m, 6H, OCH₂), 4.92 (m, 1H, CHOP). ³¹P NMR

(CDCl₃): d ꢁ2.2. ¹³C NMR (DEPT, CDCl₃): d 12.6 (s,

3

(CDCl₃): d 1.25 (t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.30

(dt,³J_HH¼ 7.1 Hz, J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.36–

4

2.08 (m, 9H, CH₂), 2.13 (s, 3H, SCH₃), 2.18–2.25 (m, 3H,

CH₂), 4.05–4–37 (m, 6H, OCH₂), 5.03 (m, 1H, CHOP). ³¹P

NMR (CDCl₃): d ꢁ1.4. ¹³C NMR (CDCl₃): d 12.6 (s,

3

SCH₃), 13.9 (s, COCH₂CH₃), 15.8 (d, J_CP¼ 6.9 Hz,

3

SCH₃), 13.6 (s, COCH₂CH₃), 15.6 (d, J_CP¼ 6.9 Hz,

POCH₂CH₃), 24.8 (s, CH₂), 27.2 [s, C(CH₃)₃], 28.7 (s, CH₂),

31.9 [s, C(CH₃)₃], 34.2 (s, CH₂), 40.7 (s, CHCCH₃), 58.3 (d,

POCH₂CH₃), 21.0, 22.1, 26.1, 29.9, 30.9 (s, CH₂), 57.5 (d,

¼

³J_CP¼ 8.5 Hz, CS), 60.6 (s, COCH₂), 63.4, 63.1 (d, J_CP

³J_CP¼ 8.4 Hz, CS), 61.4 (s, COCH₂), 63.2, 63.4 (d, J_CP

¼

2

6.1 Hz, POCH₂), 76.5 _ꢁ(d₁, J_CP¼ 5.0 Hz, CHOP), 169.9 (s,

5.0 Hz, POCH₂), 80.2 _ꢁ(d₁, J_CP¼ 5.1 Hz, CHOP), 172.6 (s,

=

C O). IR (ﬁlm): n/cm 1272 s (P O), 1713 s (C O). MS

(CI-isobutane): m/z (%) 369 (100) [M + H]⁺, 215 (50), 155

(5) [H + HOP(O)(OEt)₂]⁺. Anal. calcd for C₁₅H₂₉O₆PS

(368.48): C, 48.89; H, 7.95; P, 8.40; S, 8.43; found: C, 47.50;

H, 7.80; P, 8.61; S, 8.90%. Yield: 70%. R_f(ethyl acetate–petro-

leum ether 1:2) ¼ 0.12.

C O). IR (ﬁlm): n/cm 1247 s (P O), 1730 s (C O). MS

(CI-isobutane): m/z (%) 411 (100) [M + H]⁺, 257 (16), 155

(30). HRMS (CI) calcd for C₁₈H₃₅O₆PS + H [M + H]⁺

411.1970; found: 411.1925. Yield: 60%. R_f(ethyl acetate–petro-

leum ether 1:1) ¼ 0.28

Ethyl 2-[(diethoxyphosphoryl)oxy]-3-methyl-1-(methylsulfa-

Reaction of thiophosphates 8 and 9 with sodium borohydride

in the presence of elemental iodine. General procedure. To a sus-

pension of sodium borohydride (0.038 g, 1 mmol) in dry DME

(20 mL) was added a solution of the appropriate thiopho-

sphate (0.5 mmol) in DME (5 mL) as described above. The

reaction was monitored by TLC and after 1.5 h a solution of

iodine (0.12 g, 0.5 mmol) in dry toluene (16 mL) was added

at ꢁ78 ^ꢀC. Stirring was continued at ꢁ78 ^ꢀC for 1 h and at

room temperature for 5 h. The reaction mixture was diluted

with toluene (10 mL), washed with sodium thiosulfate (5

mL), NaOH (5 mL) and water (2 ꢃ 5 mL) and then dried with

MgSO₄. Evaporation of solvent aﬀorded the crude disulﬁdes

22 (yellow oils). No analytically pure 22 were obtained owing

to its instability during chromatography.

1

nyl)cyclohexanecarboxylate (21b). Single diastereoisomer. H

3

NMR (CDCl₃): d 1.01 (d, J_HH¼ 6.8 Hz, 3H, CHCH₃),

1.25–1.35 (m, 9H, OCH₂CH₃), 1.48–1.90 (m, 6H, CH₂), 2.13

(s, 3H, SCH₃), 2.30 (m, 1H, CH₂), 4.03–4.20 (m, 6H, OCH₂),

4.75 (dd, J_HP¼ ³J_HH¼ 8.5 Hz, 1H, CHOP). ³¹P NMR

3

(CDCl₃): d ꢁ2.0. ¹³C NMR (CDCl₃): d 12.3 (s, SCH₃),

3

13.9 (s, COCH₂CH₃), 15.9 (d, J_CP¼ 7.0 Hz, POCH₂CH₃),

17.8 (s, CHCH₃), 20.8, 31.1, 32.0 (s, CH₂), 34.0 (s, CHCH₃),

2

57.9 (s, CS), 61.4 (s, COCH₂), 63.3, 63.6 (d, J_CP¼ 6.0 Hz,

2

=

POCH₂), 84.0 (d, J_CP¼ 5.8 Hz, CHOP), 171.5 (s, C O).

IR (ﬁlm): n/cm^ꢁ11250 s (P O), 1732 s (C O). MS (CI-iso-

butane): m/z (%) 369 (100) [M + H]⁺, 215 (10). Anal. calcd

for C₁₅H₂₉O₆PS (368.48): C, 48.90; H, 7.93; P, 8.41; S, 8.70;

found: C, 48.88; H, 8.07; P, 8.21; S, 7.98%. Yield: 86%. R_f

(ethyl acetate) ¼ 0.54.

=

Bis{[1-carboethoxy-2-(diethoxyphosphoryl)oxy]cyclopentan-

1-yl} disulﬁde (22a). ¹H NMR (CDCl₃): d 1.25, 1.26 (t,

³J_HH¼ 7.0 and 7.2 Hz, 6H, COCH₂CH₃), 1.29, 1.30, 1.32 (t,

³J_HH¼ 7.0 Hz, 12H, POCH₂CH₃), 1.64–2.46 (m, 12H,

Ethyl 2-[(diethoxyphosphoryl)oxy]-4-methyl-1-(methylsulfa-

1

nyl)cyclohexanecarboxylate (21c). Single diastereoisomer. H

3

NMR (CDCl₃): d 0.95 (d, J_HH¼ 6.3 Hz, 3H, CHCH₃), 1.29

CH₂), 4.04–4.23 (m, 12H, OCH₂), 5.03 (ddd, J_HP¼ 9.9 Hz,

3

(t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.30 (dt, J_HH¼ 7.1

³J_HP¼ 5.4 Hz, J_HH¼ 4.6 Hz, 1H, CHOP). ³¹P NMR

4

Hz, J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.35–1.48 (m, 4H,

(CDCl₃): d ꢁ2.0. ¹³C NMR (CDCl₃): d 13.7 (s, COCH₂CH₃),

CH₂), 1.74–2.15 (m, 4H, CH₂), 2.14 (s, 3H, SCH₃), 4.05–4.28

15.7, 15.9 (s, POCH₂CH₃), 19.6, 30.7, 31.0,31.8 (s, CH₂), 61.5

3

2

(m, 6H, OCH₂), 4.97 (ddd, J_HH¼ 4.2 Hz, J_HP¼ 6.7 Hz,

(s, COCH₂), 61.7 (s, COCH₂), 63.6, 63.7 (d, J_CP¼ 7.3 Hz,

³J_HH¼ 11.2 Hz, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ2.2.

POCH₂), 66.2, 66.3 (d, J_CP¼ 8.7 Hz, CS), 82.5, 82.8 (d,

3

¹³C NMR (DEPT, CDCl₃):

d

12.4 (s, SCH₃), 13.8

J_CP¼ 4.8 Hz, CHOP), 170.3, 170.1 (s, C O). IR (ﬁlm):

2

=

3

n/cm^ꢁ11240 s (P O), 1726 s (C O). MS (CI-isobutane):

m/z (%) 651 (100) [M + H]⁺, 325 (4) [M/2]⁺. HRMS (EI)

calcd for C₂₄H₄₄O₁₂P₂S₂[M]⁺650.1749; found: 650.1745.

Yield: 98%. R_f(ethyl acetate) ¼ 0.26.

=

(s, COCH₂CH₃), 15.7 (d, J_CP¼ 6.9 Hz, POCH₂CH₃), 21.2

(s, CHCH₃), 28.4 (s, CH₂), 30.5 (s, CHCH₃), 31.9, 36.6 (s,

3

CH₂), 57.4 (d, J_CP¼ 8.3 Hz, CS), 61.2 (s, COCH₂), 63.1,

2

63.3 (d, J_CP¼ 6.9 Hz, POCH₂), 79.5 (d, J_CP¼ 5.3 Hz,

ꢁ1

=

CHOP), 171.9 (s, C O). IR (ﬁlm): n/cm 1260 s (P O),

Bis{[1-carboethoxy-2-(diethoxyphosphoryl)oxy]cyclohexane-

1-yl} disulﬁde (22b). ¹H NMR (CDCl₃): d 1.25 (s, 6H,

COCH₂CH₃), 1.33, 1.35 (t, ³J_HH¼ 7.0 Hz, 12H, POCH₂CH₃),

1.47–1.82 (m, 12H, CH₂), 2.18 (brd, ³J_HH¼ 8.0 Hz, 4H, CH₂),

=

1733 s (C O). MS (CI-isobutane): m/z (%) 369 (100)

[M + H]⁺, 215 (8). Anal. calcd for C₁₅H₂₉O₆PS (368.48): C,

48.90; H, 7.93; P, 8.41; S, 8.70; found: C, 47.88; H, 7.88; P,

8.28; S, 8.36%. Yield: 62%. R_f(ethyl acetate) ¼ 0.52.

3

4.10–4.30 (m, 12H, OCH₂), 4.94 (ddd, J_HH¼ 15.2 Hz,

3

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-phenyl-1-(methylsulfa-

³J_HP¼ 7.0 Hz, J_HH¼ 3.5 Hz, 1H, CHOP). ³¹P NMR

1

nyl)cyclohexanecarboxylate (21d). Single diastereoisomer. H

(CDCl₃): d ꢁ2.0, ꢁ2.11. ¹³C NMR (CDCl₃): d 13.9 (s,

NMR (CDCl₃): d 1.20 (t, 3H, COCH₂CH₃), 1.15–1.40 (m,

4H, POCH₂CH₃) 1.45–2.10 (m, 4H, CH₂), 2.20 (s, 3H,

COCH₂CH₃), 15.8, 15.9 (s, POCH₂CH₃), 22.4, 24.1, 31.7,

2

33.4, 33.7 (s, CH₂), 62.6, 63.5 (d, J_CP¼ 4.3 Hz, POCH₂),

New J. Chem., 2002, 26, 1753–1767

1763

View Article Online

3

63.2 (s, COCH₂), 65.7, 65.8 (d, J_CP¼ 7.0 Hz, CS), 81.2 (d,

9.00; found: C, 43.43; H, 8.21; P, 8.39; S, 8.79%. Yield: 87%.

R_f(ethyl acetate) ¼ 0.12.

²J_CP¼ 4.2 Hz, CHOP), 82.6 (s, CHOP), 172.2, 172.4 (s,

ꢁ1

=

C O). IR (ﬁlm): n/cm 1236 s, 1260 s (P O), 1720 s, 1731

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulﬁnyl)cyclo-

hexanecarboxylate (27b). The ratio of diastereoisomers is

1.6:1. Major isomer of 27b: ¹H NMR (CDCl₃): d 1.33 (t,

+

=

s (C O). MS (CI-isobutane): m/z (%) 679 [M + H] (100),

341 [M/2 + 2H]⁺(40), 155 [H + HOP(O)(OEt)₂]⁺(88). HRMS

(CI) calcd. for C₂₆H₄₈O₁₂P₂S₂+ H [M + H]⁺679.2141; found:

679.2144. Yield: 90%. R_f(ethyl acetate–hexane 1.5:1) ¼ 0.12.

Bis{[1-carboethoxy-2-(diethoxyphosphoryl)oxy-3-methyl]cy-

clohexan-1-yl} disulﬁde (22c). ¹H NMR (CDCl₃): d 1.97 (d,

3

³J_HH¼ 7.0 Hz, 3H, COCH₂CH₃), 1.37 (dt, J_HH¼ 7.0 Hz,

⁴J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.45–1.60 (m, 3H, CH₂),

1.93–2.20 (m, 4H, CH₂), 2.55 (m, 1H, CH₂), 2.08 (s, 3H,

SCH₃), 4.00–4.25 (m, 4H, POCH₂), 4.20–4.46 (m, 2H,

COCH₂), 5.05 (m, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ1.7.

¹³C NMR (DEPT, CDCl₃): d 14.0 (s, COCH₂CH₃), 15.7 (d,

³J_CP¼ 6.7 Hz, POCH₂CH₃), 18.2, 22.2, 24.2, 29.2 (s, CH₂),

³J_HH¼ 7.0 Hz, 3H, CHCH₃), 1.03 (d, J_HH¼ 6.5 Hz, 3H,

3

CHCH₃), 1.27 (t, J_HH¼ 4.9 Hz, 6H, OCH₂CH₃), 1.31 (t,

³J_HH¼ 4.4 Hz, 6H, POCH₂CH₃), 1.34 (t, J_HH¼ 4.6 Hz,

3

2

POCH₂CH₃), 1.44–1.61 (m, 4H, CH₂), 1.64–1.91 (m, 4H,

CH₂), 2.01–2.26 (m, 4H, CH₂), 2.28–2.36 (m, 2H, CH₂),

33.7 (s, SCH₃), 61.6 (s, COCH₂), 63.6, 63.7 (d, J_CP¼ 5.4

3

2

Hz, POCH₂), 69.8 (d, J_CP¼ 8.5 Hz, CS), 73.6 (d, J_CP

¼

4.02–4.27 (m, 12H, OCH₂), 4.51 (dd, J_HP¼ ³J_HH¼ 9.7 Hz,

3.6 Hz, CHOP), 165.7 (s, C O). IR (ﬁlm): n/cm 1264 s

3

ꢁ1

=

1H, CHOP), 4.67 (dd, J_HP¼ ³J_HH¼ 8.1 Hz, 1H, CHOP).

(P O), 1729 s (C O). MS (CI-isobutane): m/z (%) 371 (100)

[M + H]⁺, 155 (12). HRMS (CI) calcd for C₁₄H₂₇O₇PS + H

[M + H]⁺371.1293; found: 371.1305. Yield: 46%. R_f(ethyl

acetate) ¼ 0.14. Minor isomer of 27b: ¹H NMR (CDCl₃): d

3

=

³¹P NMR (CDCl₃): d ꢁ2.0. ¹³C NMR (CDCl₃): d 13.3 (s,

COCH₂CH₃), 15.5, 15.7 (s, POCH₂CH₃), 19.2, 19.6 (s, CH-

CH₃), 22.4, 27.3, 30.9 (s, CH₂), 37.1 (s, CHCH₃), 61.8 (s,

2

3

COCH₂), 63.2, 63.4 (d, J_CP¼ 7.5 Hz, POCH₂), 64.1, 64.3

1.33 (t, J_HH¼ 7.0 Hz, 3H, COCH₂CH₃), 1.35 (dt, J_HH¼

3

2

4

(d, J_CP¼ 8.7 Hz, CS), 83.2 (d, J_CP¼ 4.4 Hz, CHOP), 84.0

7.0 Hz, J_HP¼ 1.0 Hz, 6H, POCH₂CH₃), 1.48–2.45 (m, 8H,

CH₂), 2.47 (s, 3H, SCH₃), 4.05–4.45 (m, 6H, OCH₂), 5.32

(m, 1H, CHOP). ³¹P NMR (CDCl₃): d ꢁ2.4. ¹³C NMR

ꢁ1

=

(s, CHOP), 171.3, 171.4 (s, C O). IR (ﬁlm): n/cm 1234 s,

=

1262 s (P O), 1730 s, 1725 s (C O). MS (EI, 70 eV): m/z

(%) 706 (14) [M]⁺, 354 (16) [M/2 + H]⁺, 321 (53), 155 (100)

[H + HOP(O)(OEt)₂]⁺. HRMS (EI) calcd for C₂₈H₅₂O₁₂P₂S₂

[M]⁺706.2376; found: 706.2374. Yield: 53%. R_f(hexane–ethyl

acetate 1:1.5) ¼ 0.19.

3

(DEPT, CDCl₃): d 14.2 (s, COCH₂CH₃), 16.0 (d, J_CP¼ 6.9

Hz, POCH₂CH₃), 17.8, 22.3, 22.7, 28.8 (s, CH₂), 33.5 (s,

2

SCH₃), 61.9 (s, COCH₂), 63.8, 64.0 (d, J_CP¼ 5.8 Hz,

3

2

POCH₂), 70.7 (d, J_CP¼ 10.2 Hz, CS), 72.3 (d, J_CP¼ 3.6

ꢁ1

=

Bis{[1-carboethoxy-2-(diethoxyphosphoryl)oxy]cycloheptan-

1-yl} disulﬁde (22d). ¹H NMR (CDCl₃): d 1.25 (s, 6H,

COCH₂CH₃), 1.32, 1.33 (t, ³J_HH¼ 7.0 Hz, 12H, POCH₂CH₃),

1.40–2.05 (m, 16H, CH₂), 2.13–2.31 (m, 4H, CH₂), 4.11–4.33

(m, 12H, OCH₂), 5.01 (brs, 2H, CHOP). ³¹P NMR (CDCl₃):

d ꢁ2.1. ¹³C NMR (CDCl₃): d 14.1 (s, COCH₂CH₃), 16.32 (s,

POCH₂CH₃), 21.5, 24.5, 26.5, 29.7, 31.8 (s, CH₂), 61.5 (s,

Hz, CHOP), 165.8 (s, C O). IR (ﬁlm): n/cm

1262 s

=

(P O), 1732 s (C O). MS (CI-isobutane): m/z (%) 371 (100)

[M + H]⁺, 155 (17). HRMS (CI) calcd for C₁₄H₂₇O₇PS + H

[M + H]⁺371.1293; found: 371.1306. Yield: 29%. R_f(ethyl

acetate) ¼ 0.17.

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulﬁnyl)cyclo-

heptanecarboxylate (27c). The ratio of diastereoisomers is

2.5:1. Mixture of two isomers of 27c: ¹H NMR (CDCl₃): d

COCH₂), 64.5, 65.0 (br s, POCH₂), 67.1, 67.5 (s, CS), 79.4,

ꢁ1

3

=

80.5 (br s, CHOP), 171.0 (s, C O). IR (ﬁlm): n/cm 1260 s

1.29 (t, J_HH¼ 7.1 Hz, 6H, COCH₂CH₃), 1.31 (m, 12H,

=

(P O), 1720 s, 1731 s (C O). MS (CI-isobutane): m/z (%)

707 (28) [M + H]⁺, 355 (50) [M/2 + 2H]⁺, 169 (83), 155

(100) [H + HOP(O)(OEt)₂]⁺. HRMS (CI) calcd for

C₂₈H₅₂O₁₂P₂S₂+ H [M + H]⁺707.2459; found: 707.2454.

Yield: 55%. R_f(ethyl acetate–hexane 1.5:1) ¼ 0.12.

POCH₂CH₃), 1.30–1.80 (m, 12H, CH₂), 1.90–2.41 (s, 8H,

CH₂), 2.43 (s, 3H, SCH₃, minor), 2.59 (s, 3H, SCH₃, major),

4.00–4.28 (m, 12H, OCH₂), 5.07 (ddd, ³J_HP¼ ³J_HH¼ 7.0 Hz,

³J_HH< 1 Hz, 1H, CHOP, major), 5.38 (ddd, J_HP

¼

3

³J_HH¼ 5.9 Hz, J_HH< 1 Hz, 1H, CHOP, minor). ³¹P NMR

3

(CDCl₃): d ꢁ1.4 (major), ꢁ2.4 (minor). ¹³C NMR (CDCl₃):

3

Oxidation of sulﬁdes 17 and 21 to sulfoxides 27 and 28. Gen-

eral procedure. A solution of 85% m-chloroperbenzoic acid

(0.086 g. 0.5 mmol) in dichloromethane (30 mL) was added

dropwise to the appropriate sulﬁde (0.5 mmol) in dichloro-

methane (20 mL) at ꢁ78 ^ꢀC. Stirring was continued at

ꢁ78 ^ꢀC for 2 h and the reaction mixture was diluted with

Et₂O (ml), washed with sodium thiosulfate (2 ꢃ 5 mL), potas-

sium hydrogen carbonate (2 ꢃ 5 mL) and water (2 ꢃ 5 mL).

The organic layer was dried over MgSO₄and concentrated

under reduced pressure. The residue was chromatographed

on silica gel with ethyl acetate–methanol (50:1) as a eluent to

provide pure sulfoxides (colourless oils) as a mixture of two

diastereoisomers that were not separable by chromatography.

Ethyl 2-[(diethoxyphosphoryl)oxy]-1-(methylsulﬁnyl)cyclo-

pentanecarboxylate (27a). The ratio of diastereoisomers is

1:1. Mixture of two isomers of 27a: ¹H NMR (CDCl₃): d

1.15–1.45 (m, 18H, COCH₂CH₃), 1.57–2.18 (m, 10H, CH₂),

d 14.2 (d, J_CP¼ 7.5 Hz, POCH₂CH₃), 16.0 (s, COCH₂CH₃),

21.0, 25.4, 27.5 (s, CH₂), 30.8 (s, CH₂, minor), 31.5 (s, CH₂,

major), 31.7 (s, SCH₃, major), 32.4 (s, SCH₃, minor), 35.2

(s, CH₂, major), 62.4 (s, CS, major), 62.7 (s, CS, minor),

2

63.7, 64.2 (d, J_CP¼ 5.8 Hz, POCH₂), 81.5 (d, J_CP¼ 5.8

2

Hz, CHOP, major), 82.6 (d, J_CP¼ 4.8 Hz, CHOP, minor),

=

166.9 (s, C O, minor), 168.7 (s, C O, major). IR (ﬁlm):

n/cm^ꢁ11037 s (S O), 1247 s (P O), 1710 s (C O). MS (CI-

isobutane): m/z (%) 385 (48) [M + H]⁺, 321 (100), 155 (94)

[H + HOP(O)(OEt)₂]⁺; (EI, 70 eV): m/z (%) 384 (8) [M]⁺,

167 (19), 155 (100). Anal. calcd for C₁₅H₂₉O₇PS (384.47): C,

46.86; H, 7.62; P, 8.05; S, 8.34; found: C, 46.93; H, 7.91; P,

7.81; S, 8.02%. Yield: 61%. R_f(ethyl acetate) ¼ 0.16.

=

Ethyl 2-[(diethoxyphosphoryl)oxy]-3-methyl-1-(methylsulﬁ-

nyl)cyclohexanecarboxylate (28b). The ratio of diastereo-

isomers is 1:1. Fast isomer of 28b: H NMR (CDCl₃): d 0.97

(d, J_HH¼ 7.2 Hz, 3H, CHCH₃), 1.33 (t, J_HH¼ 7.2 Hz,

9H, OCH₂CH₃), 1.45–2.20 (m, 5H, CH₂), 2.23 (m, 1H,

CH₂), 2.38 (m, 1H, CH), 2.72 (s, 3H, SCH₃), 4.08–4.40 (m,

1

3

2.20–2.36 (m, 2H, CH₂), 2.48 (s, 3H, SCH₃), 2.50 (s., 3H,

¼

3

SCH₃), 4.00–4.40 (m, 12H, OCH₂), 5.13 (ddd, J_HH

3

³J_HP¼ 6.6 Hz, J_HH¼ 12.9 Hz, 1H, CHOP), 5.47 (m, 1H,

6H, OCH₂), 4.93 (dd, J_HP¼ 5.7 Hz, J_HH¼ 7.6 Hz, 1H,

CHOP). ³¹P NMR (CDCl₃): d ꢁ2.0, ꢁ2.4. ¹³C NMR (DEPT,

CHOP). ³¹P NMR (CDCl₃): d ꢁ2.0. ¹³C NMR (DEPT,

3

CDCl₃): d 13.5, 13.7 (s, COCH₂CH₃), 15.5 (d, J_CP¼ 6.3 Hz,

CDCl₃): d 14.1 (s, COCH₂CH₃), 16.0 (d, J_CP¼ 6.7 Hz,

POCH₂CH₃), 20.5, 24.7, 27.0, 31.9, 32.6 (s, CH₂), 34.6 (s,

POCH₂CH₃), 16.9 (s, CHCH₃), 18.4, 26.2, 27.4 (s, CH₂),

34.3 (s, SCH₃), 35.2 (s, CHCH₃), 61.9 (s, COCH₂), 63.8, 64.0

2

SCH₃), 62.0 (d, J_CP¼ 6.2 Hz, POCH₂), 63.6 (s, COCH₂),

3

2

3

74.0 (d, J_CP¼ 8.4 Hz, CS), 80.5 (d, J_CP¼ 4.9 Hz, CHOP),

(d, J_CP¼ 6.8 Hz, POCH₂), 68.7 (d, J_CP¼ 7.1 Hz, CS),

ꢁ1

2

=

1264 s (P O), 1729 s

=

170.8 (s, C O). IR (ﬁlm): n/cm

80.9 (d, J_CP¼ 5.1 Hz, CHOP), 167.1 (s, C O). IR (ﬁlm):

+

(C O). MS (CI-isobutane): m/z (%) 357 (100) [M + H] . Anal.

calcd for C₁₃H₂₅O₇PS (356.42): C, 43.80; H, 7.08; P, 8.69; S,

n/cm^ꢁ11256 s (P O), 1728 s (C O). MS (CI-isobutane): m/z

=

(%) 385 (100) [M + H]⁺, 321 (24). Anal. calcd for C₁₅H₂₉O₇PS

1764

New J. Chem., 2002, 26, 1753–1767

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3

(384.42): C, 46.87; H, 7.60; P, 8.06; S, 8.34; found: C, 46.35; H,

7.64; P, 7.43; S, 8.49%. Yield: 44%. R_f(ethyl acetate) ¼ 0.19.

COCH₂), 4.00–4.32 (m, 4H, POCH₂), 4.90 (ddd, J_HH¼ 8.7

Hz, J_HP¼ ³J_HH¼ 7.3 Hz, 1H, CHOP), 7.10–7.42 (m, 5H,

3

Slow isomer of 28b: ¹H NMR (CDCl₃): d 0.93 (d, J_HH

¼

CH_arom). ³¹P NMR (CDCl₃): d ꢁ2.1. ¹³C NMR (CDCl₃): d

3

7.8 Hz, 3H, CHCH₃), 1.22–1.35 (m, 9H, OCH₂CH₃), 1.40–

2.10 (m, 6H, CH₂), 2.38 (m, 1H, CH₂), 2.38 (s, 3H, SCH₃),

2.62 (m, 1H, CHCH₃), 4.05–4.40 (m, 6H, OCH₂), 5.15 (dd,

13.8 (s, COCH₂CH₃), 15.9 (d, J_CP¼ 6.8 Hz, POCH₂CH₃),

28.6, 29.5, (s, CH₂), 34.9 (s, SCH₃), 37.5 (s, CH), 37.9 (s,

CH₂), 61.9 (s, COCH₂), 63.6, 63.9 (d, ²J_CP¼ 6.0 Hz, POCH₂),

3

2

³J_HP¼ 3.4 Hz, J_HH¼ 5.4 Hz, 1H, CHOP). ³¹P NMR

69.0 (d, J_CP¼ 8.7 Hz, CS), 76.8 (d, J_CP¼ 4.8 Hz, CHOP),

(CDCl₃): d ꢁ2.4. ¹³C NMR (DEPT, CDCl₃): d 14.1 (s, CO-

126.4, 126.6, 128.5, 143.1 (s, CH_arom) 167.5 (s, C O). IR

=

(KBr): n/cm^ꢁ11271 s (P O), 1735 s (C O). MS (CI-iso-

butane): m/z (%) 447 (100) [M + H]⁺. Anal. calcd for

C₂₀H₃₁O₇PS (446.55): C, 53.80; H, 7.00; P, 6.94; S, 7.18; found:

C, 54.21; H, 7.12; P, 7.13; S, 7.25%. Yield: 25%. R_f(ethyl acet-

ate) ¼ 0.25.

3

=

CH₂CH₃), 15.9 (d, J_CP¼ 6.9 Hz, POCH₂CH₃), 16.1 (s,

CHCH₃), 17.1, 23.0, 27.4 (s, CH₂), 33.5 (s, CHCH₃), 61.8 (s,

2

COCH₂), 63.7, 64.0 (d, J_CP¼ 6.5 Hz, POCH₂), 68.3 (d,

2

²J_CP¼ 9.3 Hz, CS), 77.8 (d, J_CP¼ 4.4 Hz, CHOP), 166.3

ꢁ1

=

(s, C O). IR (ﬁlm): n/cm 1024 s (S O), 1254 s (P O),

=

1718 s (C O). MS (CI-isobutane): m/z (%) 385 (100)

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-tert-butyl-1-(methylsulﬁ-

nyl)cyclohexanecarboxylate (28e). The ratio of diastereo-

isomers is 1.8:1. Mixture of two isomers of 28e: ¹H NMR

(500 MHz, CDCl₃): d 0.85 (s, 9H, CCH₃, major), 0.88 (s,

9H, CCH₃, minor), 1.20–1.45 (m, 18H, OCH₂CH₃), 1.42 (m,

1H, CH₂), 1.52–1.70 (m, 2H, CH₂), 1.75–1.93 (m, 2H, CH₂),

2.05–2.47 (m, 8H, CH, CH₂), 2.65 (m, 1H, CH, minor), 2.71

(s, 3H, SCH₃, minor), 2.83 (s, 3H, SCH₃, major), 4.00–4.47

(m, 12H, OCH₂), 5.01 (m, 1H, CHOP, minor), 5.16 (m, 1H,

CHOP, major). ³¹P NMR (CDCl₃): d ꢁ1.4 (minor), ꢁ2.2

(major). ¹³C NMR (CDCl₃): d 14.0 (s, COCH₂CH₃, major),

[M + H]⁺321 (7). Anal. calcd for C₁₅H₂₉O₆PS (384.42): C,

46.87; H, 7.60; P, 8.06; S, 8.34; found: C, 46.47; H, 7.60; P,

8.20; S, 7.81%. Yield: 41%. R_f(ethyl acetate) ¼ 0.14.

Ethyl 2-[(diethoxyphosphoryl)oxy]-4-methyl-1-(methylsulﬁ-

nyl)cyclohexanecarboxylate (28c). The ratio of diastereo-

isomers is 2.1:1. Mixture of two isomers of 28c: ¹H NMR

3

(CDCl₃): d 0.99 (d, J_HH¼ 6.0 Hz, 3H, CHCH₃, major),

3

1.07 (d, J_HH¼ 6.9 Hz, 3H, CHCH₃, minor), 1.32 (t,

³J_HH¼ 7.1 Hz, 3H, COCH₂CH₃, minor), 1.33 (dt, J_HH

¼

3

4

7.0 Hz, J_HP¼ 1.1 Hz, 6H, POCH₂CH₃, minor), 1.34 (dt,

³J_HH¼ 7.0 Hz, J_HP¼ 1.1 Hz, 6H, POCH₂CH₃, major),

14.2 (s, COCH₂CH₃, minor), 15.9 (d, J_CP¼ 4.0 Hz,

4

3

1.35 (t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃, major), 1.43–2.25

POCH₂CH₃), 23.8 (s, CH₂), 26.8 [s, C(CH₃)₃], 29.5 (s, CH₂),

31.1 (s, SCH₃), 32.4 [s, C(CH₃)₃], 34.2 (s, CH₂), 41.6 (s,

CHCCH₃), 61.6 (s, COCH₂, minor), 61.9 (s, COCH₂, major),

(m, 14H, CH, CH₂), 2.68 (s, 3H, SCH₃, minor), 2.74 (s, 3H,

SCH₃, minor), 4.00–4.46 (m, 12H, OCH₂), 5.05 (m, 1H,

CHOP, major), 5.26 (ddd, J_HH¼ ³J_HP¼ 4.1 Hz, J_HH

¼

63.5, 63.9 (d, J_CP¼ 6.4 Hz, POCH₂), 68.5 (d, ³J_CP¼ 8.0 Hz,

3

2

7.1 Hz, 1H, CHOP, minor). ³¹P NMR (CDCl₃): d ꢁ1.9

CS, minor), 70.1 (d, J_CP¼ 8.4 Hz, CS, major), 77.4 (_ꢁd₁,

3

(major), ꢁ2.4 (minor). ¹³C NMR (CDCl₃):

d

14.1 (s,

J_CP¼ 5.0 Hz, CHOP), 167.9 (s, C O). IR (ﬁlm): n/cm

2

=

3

=

COCH₂CH₃), 16.0 (d, J_CP¼ 7.2 Hz, POCH₂CH₃), 20.7 (s,

CHCH₃, minor), 21.2 (s, CHCH₃, major), 25.3 (s, CH₂),

27.4 (s, CHCH₃, minor), 28.4 (s, CH₂, major), 28.6 (s,

CH₂,minor), 29.1 (s, CHCH₃, major), 29.6 (s, SCH₃, major),

34.3 (s, CH₂,minor), 37.4 (s, SCH₃, minor), 61.6 (s, COCH₂,

1263 s (P O), 1739 s (C O). MS (CI-isobutane): m/z (%)

427 (100) [M + H]⁺. Anal. calcd for C₁₈H₃₅O₇PS (426.57): C,

50.68; H, 8.29; P, 7.26; S, 7.52; found: C, 49.98; H, 7.92; P,

6.60; S, 7.10%. Yield: 62%. R_f(ethyl acetate) ¼ 0.19.

2

major), 61.9 (s, COCH₂, minor), 63.7, 64.0 (d, J_CP¼ 6.0 Hz,

2

POCH₂), 70.0 (d, J_CP¼ 9.0 Hz, CS), 75.5 (d, J_CP¼ 4.8 Hz,

Preparation of 2-alkenyl phosphates 29 and 30. General pro-

cedure. A solution of the appropriate sulfoxide (0.4 mmol) in

dry toluene (5 mL) or, in the case of 27a, in dry benzene (5

mL), was stirred at 100 ^ꢀC or, in the case of 27a, at 70 ^ꢀC,

for 3–6 h (depending on the sulfoxide). The progress of the

reaction was followed by TLC chromatography. When the

reaction was complete, solvent and volatile products were

removed in vacuo and the residue was puriﬁed by silica gel

chromatography (petroleum ether–ethyl acetate 10:3) to

provide pure phosphates 29 and 30

2

CHOP, minor), 77.0 (d, J_CP¼ 5.0 Hz, CHOP, major),167.0

ꢁ1

=

= =

1016 s (S O),1246 s (P O),

(s, C O). IR (ﬁlm): n/cm

=

1725 s (C O). MS (CI-isobutane): m/z (%) 385 (100)

[M + H]⁺. Anal. calcd for C₁₅H₂₉O₇PS (384.42): C, 46.87; H,

7.60; P, 8.06; S, 8.34; found: C, 46.50; H, 7.10; P, 7.77; S,

7.65%. Yield: 76%. R_f(ethyl acetate) ¼ 0.15.

Ethyl 2-[(diethoxyphosphoryl)oxy]-5-phenyl-1-(methylsulﬁ-

nyl)cyclohexanecarboxylate (28d). The ratio of diastereo-

isomers is 2:1. Major isomer of 28d: ¹H NMR (CDCl₃): d

3

4

1.12 (dt, J_HH¼ 7.1 Hz, J_HP¼ 1.0 Hz, 3H, POCH₂CH₃),

3

1.18 (t, J_HH¼ 7.2 Hz, 3H, COCH₂CH₃), 1.29 (dt, J_HH

¼

4

7.2 Hz, J_HP¼ 1.0 Hz, 3H, POCH₂CH₃), 1.50–2.62 (m, 8H,

CH₂, SCH₃), 3.00 (dddd, ³J_HH¼ ³J_HH¼ 12.4 Hz,

³J_HH¼ ³J_HH¼ 3.2 Hz, 1H, CHPh), 3.18 (m, 1H, CH₂),

3.82–4.12 (m, 6H, COCH₂), 4.09–4.32 (m, 4H, POCH₂), 5.04

Preparation of 2-alkenyl phosphates 29 and 30 directly from

b-keto esters 10 and 11. Thiophosphates 8 and 9 were prepared

by the reaction of the appropriate enolate anion of b-keto-

esters 10 and 11 (generated with NaH in THF solution at

0 ^ꢀC) with freshly prepared diethoxyoxophosphoranesulfenyl

chloride 1, performed at ꢁ78 ^ꢀC, as described above. Work-

up followed by evaporation of solvents under reduced pressure

aﬀorded crude thiophosphate 8 or a crude mixture of diaster-

eoisomers of thiophosphate 9, which was added dropwise to

a suspension of sodium borohydride at ꢁ78 ^ꢀC, followed

by addition of excess (5 equiv) methyl iodide. Stirring was con-

tinued at ꢁ78 ^ꢀC and the reaction was stopped after 5–7 h by

addition of EtOAc and ice water. After standard work-up (see

above) the crude reaction mixture containing sulﬁde 17 or 21

among other products [episulﬁde 15 (19) and oleﬁn 16 (20)]

was oxidized with 85% MCPBA in CH₂Cl₂solution at

ꢁ78 ^ꢀC. After stirring at ꢁ78 ^ꢀC for 2 h, Et₂O was added

and the mixture was washed with Na₂S₂O₃, NaHCO₃, water

and dried (MgSO₄). Evaporation of solvent followed by ﬂash

chromatography [silica gel, EtOAc–MeOH (50:1) as eluent]

aﬀorded pure sulfoxide 27 (28). Compound 27 (28) was

3

(ddd, J_HH¼ 12.9 Hz, J_HP¼ 7.8 Hz, J_HH¼ 5.1 Hz, 1H,

CHOP), 7.10–7.45 (m, 5H, CH_arom). ³¹P NMR (CDCl₃): d

ꢁ2.3. ¹³C NMR (DEPT, CDCl₃): d 13.8 (s, COCH₂CH₃),

3

15.9 (d, J_CP¼ 6.8 Hz, POCH₂CH₃), 28.6, 29.6 (s, CH₂),

34.9 (s, SCH₃), 37.5 (s, CHPh), 37.9 (s, CH₂), 61.9 (s, COCH₂),

2

3

63.6, 63.8 (d, J_CP¼ 6.0 Hz, POCH₂), 68.0 (d, J_CP¼ 8.7 Hz,

CS), 76.8 (d, ²J_CP¼ 4.8 Hz, CHOP), 126.4, 126.6, 128.5, 143.1

ꢁ1

=

(s, CH_arom) 167.5 (s, C O). IR (KBr): n/cm 1269 s (P O),

=

1736 s (C O). MS (CI-isobutane): m/z (%) 446 (100)

[M + H]⁺. Anal. calcd for C₂₀H₃₁O₇PS (446.55): C, 53.80; H,

7.00; P, 6.94; S, 7.18; found: C, 54.15; H, 7.24; P, 7.11; S,

7.10%. Yield: 48%. R_f(ethyl acetate) ¼ 0.20. Minor isomer

of 28d: ¹H NMR (CDCl₃): d 1.18 (t, J_HH¼ 7.1 Hz, 3H,

3

4

COCH₂CH₃), 1.32 (dt, J_HH¼ 7.1 Hz, J_HP¼ 1.0 Hz, 3H,

POCH₂CH₃), 1.55–2.41 (m, 8H, CH₂, SCH₃), 2.62 (m,

¼

3

1H, CH₂), 2.90 (dddd, J_HH¼ ³J_HH¼ 3.3 Hz, J_HH

³J_HH¼ 12.3 Hz, 1H, CHPh), 3.98 (q, J_HH¼ 7.1 Hz, 2H,

3

New J. Chem., 2002, 26, 1753–1767

1765

View Article Online

dissolved in dry toluene (27a in dry benzene) and heated with

stirring, at 100 ^ꢀC (27a at 70 ^ꢀC) for a few hours. When the

reaction was complete (monitoring of the reaction progress

by TLC), solvent and volatile products were removed in vacuo

and the residue was chromatographed on silica gel with n-

hexane–ethyl acetate (10:3) to aﬀord a pure phosphates 29

and 30 as colourless oils.

[M + H]⁺321.1467; found: 321.1475. Yield: 84%. R_f(ethyl

acetate) ¼ 0.54.

Ethyl 6-[(diethoxyphosphoryl)oxy]-4-methylcyclohex-1-ene-1-

carboxylate (30c). Single diastereoisomer. ¹H NMR (500

3

MHz, CDCl₃): d 1.02 (d, J_HH¼ 6.3 Hz, 3H, CHCH₃) 1.15–

1.45 (m, 9H, OCH₂CH₃), 1.52–2.00 (m, 3H, CH, CH₂), 2.13–

2.35 (m, 2H, CH₂), 4.00–4.42 (m, 6H, OCH₂), 5.35 (m, 1H,

CHOP), 6.96 (m, 1H, CH₂CH C). ³¹P NMR (CDCl₃): d

=

Ethyl 5-[(diethoxyphosphoryl)oxy]cyclopent-1-ene-1-carboxy-

1.05–1.43 (m, 9H,

late (29a). ¹H NMR (CDCl₃):

OCH₂CH₃), 2.16–2.85 (m, 4H, CH₂), 4.05–4.42 (m, 6H,

d

ꢁ1.4. ¹³C NMR (CDCl₃): d 13.8 (s, COCH₂CH₃), 15.6 (d,

³J_CP¼ 6.9 Hz, POCH₂CH₃), 20.3 (s, CHCH₃), 27.7, 31.4,

3

2

OCH₂), 5.64 (m, 1H, CHOP), 7.13 (dd, J_HH¼ ³J_HH¼ 2.5

36.0 (s, CH₂), 62.3 (s, COCH₂), 63.5, 63.6 (d, J_CP¼ 6.8 Hz,

Hz, 1H, CH₂CH C). ³¹P NMR (CDCl₃): d ꢁ1.7. ¹³C NMR

POCH₂), 75.0 (d, J_CP¼ 5.3 Hz, CHOP), 129.3 (d, J_CP¼

= =

2

3

=

3

(CDCl₃): d 13.9 (s, COCH₂CH₃), 15.9 (d, J_CP¼ 6.9 Hz,

8.0 Hz, CH CCOOEt)_ꢁ, ₁146.4 (s, CH CCOOEt), 166.2 (s,

= = =

POCH₂CH₃), 23.0 (s, CH₂), 39.2 (s, CH₂), 61.9 (s, COCH₂),

C O). IR (KBr): n/cm 1252 s (P O), 1724 s (C O). MS

(CI- isobutane): m/z (%) 321 (100) [M + H]⁺. Anal. calcd for

C₁₄H₂₅O₆P (320.36): C, 52.48; H, 7.88; P, 9.67; found: C,

52.30; H, 7.67; P, 9.66%. Yield: 70%. R_f(ethyl acetate) ¼ 0.54.

Ethyl 6-[(diethoxyphosphoryl)oxy]-3-phenylcyclohex-1-ene-1-

2

63.1, 63.2 (d, J_CP¼ 6.5 Hz, POCH₂), 70.3 (d, J_CP¼ 5.0

=

Hz, CHOP), 130.2 (s, CH CCOOEt), 147.5 (s,

ꢁ1

=

CH CCOOEt), 166.7 (s, C O). IR (KBr): n/cm 1258 s

=

(P O), 1718 s (C O). MS (CI- isobutane): m/z (%) 293 (8)

[M + H]⁺, 155 (100) [H + HOP(O)(OEt)₂]⁺, 139 (30). Anal.

calcd for C₁₂H₂₁O₆P (292.30): C, 49.30; H, 7.26; P, 10.59;

found: C, 49.18; H, 7.06; P, 10.48%. Yield: 72%. R_f(ethyl acet-

ate–petroleum ether 1:1) ¼ 0.43.

1

carboxylate (30d). Single diastereoisomer. H NMR (CDCl₃):

3

4

d 1.32 (dt, J_HH¼ 7.1 Hz, J_HP¼ 0.8 Hz, 6H, POCH₂CH₃),

3

1.34 (t, J_HH¼ 7.1 Hz, 3H, COCH₂CH₃), 1.65–1.98 (m, 2H,

CH₂), 2.05–2.30 (m, 2H, CH₂), 3.72 (m, 1H, CH), 3.95–4.40

3

Ethyl 6-[(diethoxyphosphoryl)oxy]cyclohex-1-ene-1-carboxy-

(m, 6H, OCH₂CH₃), 5.42 (ddd, J_HH¼ 6.6 Hz, J_HP¼

late (29b). ¹H NMR (CDCl₃):

OCH₂CH₃), 1.45–1.90 (m, 4H, CH₂), 2.18–2.40 (m, 2H,

d

1.15–1.43 (m, 9H,

³J_HH¼ 3.8 Hz, 1H, CHOP), 7.10 (d, J_HH¼ 7.3 Hz, 1H,

3

CHCH C). ³¹P NMR (CDCl₃): d ꢁ1.8. ¹³C NMR (DEPT,

=

3

CH₂), 3.95–4.32 (m, 6H, OCH₂), 5.33 (ddd, J_HP¼ 6.2 Hz,

CDCl₃): d 14.1 (s, COCH₂CH₃), 16.0 (d, J_CP¼ 6.9 Hz,

3

³J_HH¼ ³J_HH¼ 3.3 Hz, 1H, CHOP), 7.20 (dd, J_HH¼ 4.9

POCH₂CH₃), 25.1 (s, CH₂), 25.7 (s, CH₂), 40.4 (s, CHPh),

3

2

Hz, J_HH¼ 2.8 Hz, 1H, CH₂CH C). ³¹P NMR (CDCl₃): d

60.7 (s, COCH₂), 63.3, 63.5 (d, J_CP¼ 6.8 Hz, POCH₂), 69.2

=

ꢁ2.0. ¹³C NMR (DEPT, CDCl₃): d 14.0 (s, COCH₂CH₃),

(d, J_CP¼ 5.1 Hz, CHOP), 126.7, 127.8, 128.5 (s, CH_arom),

2

3

=

15.4 (s, CH₂), 15.9 (d, J_CP¼ 6.9 Hz, POCH₂CH₃), 25.6 (s,

130.7 (d, J_CP¼ 8.8 Hz, CH CCOOEt), 141.9 (s, i-CH_arom

)

ꢁ1

=

CH₂), 28.9 (s, CH₂), 60.4 (s, COCH₂CH₃), 63.2, 63.4 (d,

145.3 (s, CH CCOOEt), 165.5 (s, C O). IR (KBr): n/cm

2

²J_CP¼ 7.2 Hz, POCH₂CH₃), 68.8 (d, J_CP¼ 5.3 Hz, CHOP),

1264 s (P O), 1717 s (C O). MS (EI, 70eV): m/z (%) 382

(3) [M⁺], 228 (85), 183 (10), 155 (100), 99 (16). Anal. calcd

for C₁₉H₂₇O₆P (382.43): C, 59.67; H, 7.13; P, 8.10; found: C,

59.43; H, 6.72; P, 8.23. Yield: 79%. R_f(ethyl acetate) ¼ 0.41.

Ethyl 6-[(diethoxyphosphoryl)oxy]-3-tert-butylcyclohex-1-ene-

1-carboxylate (30e). Single diastereoisomer. ¹H NMR

=

3

=

129.1 (d,

=

J_CP¼ 8.9 Hz, CH CCOOEt), 145.1 (s,

ꢁ1

=

CH CCOOEt), 165.5 (s, C O). IR (KBr): n/cm 1260 s

=

(P O), 1720 s (C O). MS (CI- isobutane): m/z (%) 307

(100) [M + H]⁺, 155 (57). HRMS (CI) calcd for

C₁₃H₂₃O₆P + H [M + H]⁺307.1311; found: 307.1317. Yield:

70%. R_f(ethyl acetate–petroleum ether 1:1) ¼ 0.47.

(CDCl₃):

d 0.91 [s, 9H, C(CH₃)₃], 1.15–1.40 (m, 9H,

OCH₂CH₃), 1.62–2.38 (m, 5H, CH₂), 3.81–4.38 (m, 6H,

Ethyl 7-[(diethoxyphosphoryl)oxy]cyclohept-1-ene-1-carboxy-

late (29c). ¹H NMR (CDCl₃):

OCH₂CH₃), 1.32–2.61 (m, 8H, CH₂), 3.92–4.23 (m, 6H,

d

1.10–1.34 (m, 9H,

OCH₂), 5.30 (m, 1H, CHOP), 7.09 (d, J_HH¼ 2.5 Hz, 1H,

3

CHCH C). ³¹P NMR (CDCl₃): d ꢁ0.8. ¹³C NMR (DEPT,

=

3

OCH₂), 5.63 (ddd, J_HH¼ ³J_HP¼ 6.4 Hz, J_HH¼ 1.2 Hz,

500 MHz, CDCl₃): d 14.2 (s, COCH₂CH₃), 16.0 (d, J_CP

7.1 Hz, POCH₂CH₃), 20.3 (s, CH₂), 27.6 [s, C(CH₃)₃], 29.5

¼

3

1H, CHOP), 7.36 (ddd, J_HH¼ 5.2 Hz, J_HH¼ 8.0 Hz,

4

J_HH¼ 1.1 Hz, 1H, CH₂CH C). ³¹P NMR (CDCl₃): d

(s, CH₂), 33.7 [s, C(CH₃)₃], 45.7 [s, CHC(CH₃)₃], 60.6 (s, CO-

=

ꢁ1.5. ¹³C NMR (CDCl₃): d 14.1 (s, COCH₂CH₃), 16.0 (d,

CH₂), 63.4, 63.6 (d, J_CP¼ 5.9 Hz, POCH₂), 71.4 (s, CHOP),

2

³J_CP¼ 6.8 Hz, POCH₂CH₃), 24.0 (s, CH₂), 25.9 (s, CH₂),

131.5 (d, J_CP¼ 9.8 Hz, CH CCOOEt),_ꢁ1145.3 (s, CH

3

=

3

=

27.7 (s, CH₂), 31.3 (d, J_CP¼ 4.2 Hz, CH₂), 60.8 (s, COCH₂),

CCOOEt), 166.1 (s, C O). IR (KBr): n/cm 1267 s (P O),

63.4, 63.6 (d, ²J_CP¼ 6.5 Hz, POCH₂), 73.3 (d, ²J_CP¼ 6.4 Hz,

1724 s (C O). MS (CI-isobutane): m/z (%) 363 (100)

=

[M + H]⁺, 309 (13), 209 (20), 155 (58). HRMS (CI) calcd for

C₁₇H₃₁O₆P + H [M + H]⁺363.1936; found: 363.1933. Yield:

68%. R_f(ethyl acetate–petroleum ether 1:1) ¼ 0.56.

=

CHOP), 134.1 (s, CH CCOOEt), 149.2 (s, CH CCOOEt),

=

ꢁ1

=

+

166.5 (s, C O) ppm. IR (KBr): n/cm 1256 s (P O), 1718 s

(C O). MS (EI, 70 eV): m/z (%) 320 (5) [M] , 155 (100)

=

[H + HOP(O)(OEt)₂]⁺, 127 (37), 99 (40). Anal. calcd for

C₁₄H₂₅O₆P (320.39): C, 52.47; H, 7.88; P, 9.69; found: C,

52.25; H, 7.10; P, 9.41%. Yield: 76%. R_f(ethyl acetate–petro-

leum ether 1:1) ¼ 0.50.

Acknowledgements

This work was supported by the State Committee for Scientiﬁc

Research, Poland (No 7T09A 148 21).

Ethyl 6-[(diethoxyphosphoryl)oxy]-5-mathylcyclohex-1-ene-1-

carboxylate (30b). Single diastereoisomer. ¹H NMR (CDCl₃):

3

d 0.89 (d, J_HH¼ 7.2 Hz, 3H, CHCH₃), 1.30 (t, J_HH¼ 7.2

Hz, 9H, OCH₂CH₃), 1.45 (m, 1H, CH₂), 1.95 (m, 1H, CH₂),

2.15–2.33 (m, 2H, CH₂), 3.95–4.36 (m, 6H, OCH₂), 5.01 (dd,

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1767

Article Doi

An expedient, stereoselective synthesis of highly functionalized cyclic compounds

DOI: 10.1039/b207700k

Source and publish data:

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Article abstract of DOI:10.1039/b207700k

Full text of DOI:10.1039/b207700k

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