(E)-1-Bromo-2-phenylthioethylene1

(E)-(1; X = Br)

[17101-82-5]  · C8H7BrS  · (E)-1-Bromo-2-phenylthioethylene  · (MW 215.11) (Z)-(2; X = Br)

[17101-71-2] (E)-(3; X = Cl)

[26620-11-1]  · C8H7ClS  · (E)-1-Chloro-2-phenylthioethylene  · (MW 170.66)

(building blocks for stereospecific synthesis of alkenes and dienes)

Alternate Name: 2-bromovinyl phenyl sulfide.

Physical Data: (1) bp 44.5-45 °C/0.04 mmHg; (2) bp 59-60 °C/0.04 mmHg; (3) bp 119-120 °C/15 mmHg.

Analysis of Reagent Purity: GC/MS, IR, and 1H NMR.

Preparative Methods: (i) 3-phenylthioacrylic acid is first formed by thiophenol addition to propiolic acid, and is then subjected to a one-pot bromine addition and subsequent decarboxylative dehalogenation. This gives a ca. 1:4 mixture of (1) and (2) (overall yield 69%);2 (ii) by a PTC reaction between thiophenol and 1,2-dibromoethylene (only isomer (2), yield 48%);3 and (iii) by addition of sulfenyl chloride to acetylene (only compound (3), yield 73%).4

Purification: by distillation; the isomeric mixture of (1) and (2) is separated into its components by careful distillation,5 or by flash chromatography (silica gel; petroleum ether eluent).

Handling, Storage, and Precautions: if refrigerated (-10 to 0 °C) they can be stored for several weeks without isomerization. Avoid inhaling; use in a fume hood.

Synthesis of Stereodefined Alkenes.

Reagents (1), (2), and (3) can be subjected to two, sequential, cross-coupling reactions with Grignard reagents in the presence of a NiII or PdII catalyst, with the substitution of the halogen and phenylthio group (eqs 1 and 2) yielding stereodefined alkenes.1,5,6

The substitution of the phenylthio group is much slower than the replacement of the halogen, and can be performed only using longer reaction times and an excess of Grignard reagent. In order to prepare nonsymmetrical alkenes, it is necessary to use a different Grignard reagent after completion of the first step.6 Often, it is unnecessary to isolate the vinyl sulfide intermediate and the procedure can be performed successfully in one pot. Moreover, the isomeric purity of the final product is higher than 99% in the case of the (E) isomers, and slightly lower for the (Z) isomers (95-98%). In the second step of the procedure (e.g. the substitution of the phenylthio group), Ni catalysts cannot be replaced by Pd catalysts.

An application of the described method is the synthesis of many monoalkenic insect sex pheromones in high isomeric purity (>98%), and in isolated overall yields in the range 65-75% for the (Z) isomers and 80-90% for the (E) isomers.5 The procedure can also be applied to the synthesis of pheromones with an alkenyl acetate structure (eqs 3 and 4), using Grignard reagents derived from 1-halo-o-tetrahydropyranyloxyalkanes in the first step, and acetylating the tetrahydropyranyl-protected alkenols after the second cross-coupling step.5

Synthesis of Stereodefined Alkenyl Sulfides.

The substitution of the halogen atom occurs at a rate much greater than the phenylthio group; thus alkenyl sulfides can be conveniently obtained (eqs 5-7).3,5,6

It is worth noting that the use of a Pd catalyst in the reaction leading to (Z) isomers gives better stereochemical results. The phenylthio group of alkenyl sulfides is easily converted to a carbonyl group.7

Alkenyl sulfides can be also obtained in an enantioselective manner (51-57% ee) by a cross-coupling reaction of (1) or (2) with a secondary Grignard reagent in the presence of chiral NiII or PdII catalysts, at 0 °C or at rt, in THF or ether (eq 8).3 The best results are obtained with the complex of the chiral phosphine PPFA (PPFA = (R)-N,N-Dimethyl-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine).

Occasionally, when secondary organomagnesium reagents are used, isomerization of the secondary alkyl/primary alkyl group is observed. Iron(III) complexes, for example Tris(dibenzoylmethide)iron(III) and Fe(DPM)3 (DPM = dipivaloylmethide), completely suppress this isomerization process.8

The cross-coupling process leading to (Z)-alkenyl sulfides can also be performed with other organometallic compounds, e.g. by combining (2) with 9-alkyl-9-BBN in the presence of Tetrakis(triphenylphosphine)palladium(0) (as catalyst) and a base,9a or with (dialkoxyboryl)methylzinc reagents in the presence of the same catalyst.9b

Reagent (E)-(3) can be transformed into vinyl selenides by action of MeSeLi or PhSeNa (eq 9), with retention of configuration.10

Synthesis of Stereodefined Dienes.

1,3-Dienes.

1-Trimethylsilyl-1,3-dienes.

(1E,3E)- and (1E,3Z)-1-trimethylsilyl-1,3-dienes can be obtained by the appropriate cross-coupling reaction between (1) or (2) and (E)-2-trimethylsilylvinylmagnesium bromide (eqs 10 and 11) in the presence of NiCl2(dppe).11

These compounds can be employed in the synthesis of more complex targets, since both the phenylthio and the trimethylsilyl groups can be substituted in different ways (e.g. the trimethylsilyl group can be replaced by acyl groups using acyl chlorides in the presence of AlCl3).1

1-Phenylthio-1,3-dienes.

Reagents (1) and (2) react with 1-alkenyl-1,3,2-benzodioxaborole in the presence of Pd(PPh3)4 and a base to yield 1-phenylthio-1,3-alkadienes or -1,3,5-alkatrienes (eqs 12 and 13).12 These intermediates are easily converted into important natural products, e.g. cis(C10)-allofarnesene, by the substitution of the arylthio group with a Grignard reagent in the presence of NiII complexes.

(E,Z)- and (Z,E)-Dienes.

Reagent (2) can give Phenylthioacetylene,2 to which (Z)-dialkenylcuprates are added (eq 14).13

The arylthio group of the resulting (E,Z)- and (Z,E)-1-phenylthio-1,3-dienes can be substituted by a Grignard reagent in the presence of NiCl2(dppe) to yield the corresponding dienes (eq 15). A variety of pheromones having a conjugated diene structure can be prepared using this approach.13

1,4-Dienes.

Phenylthiopentadiene.

Reagent (2) is converted (eq 16) by a cross-coupling reaction with Allylmagnesium Bromide in the presence of NiCl2(dppe) to a 1-phenylthio-1,4-diene.14 This compound can be easily metalated with n-Butyllithium to give phenylthiopentadienyllithium, which can be reacted with various C-electrophiles, or can be first transmetalated and then reacted with C-electrophiles. The stereo- and regiochemistry of the process can be properly tuned.

Synthesis of Sulfoxides.

Vinyl Sulfoxides.

Reagents (1), (2), and (3) can be oxidized by m-Chloroperbenzoic Acid to the corresponding sulfoxides, which react in two different ways (eq 17), according to the organometallic reagent employed.15

Organocuprates give the cross-coupling process with substitution of the halogen group. Grignard reagents attack the sulfur atom with substitution of the whole halovinyl moiety. Starting with optically active halovinyl aryl sulfoxides, alkyl aryl or diaryl sulfoxides can be obtained in a highly enantioselective manner.16

Vinylstannanes.

Reagent (3) can generate vinylstannanes after m-CPBA oxidation to sulfoxides, and subsequent treatment with Hexamethyldistannane (eq 18) in the presence of Pd2(dba)3/PPh3.17

Recently, reagent (3) has been transformed into 1-bromo-1-phenylthio-1,3-butadiene, thus leading to a general approach to conjugated (E,E)-dienes, through sequential coupling reactions.18

Related Reagents.

Phenylthioacetylene.


1. Naso, F. PAC 1988, 60, 79. Fiandanese, V. PAC 1990, 62, 1987.
2. Angeletti, E.; Montanari, F.; Negrini, A. G 1957, 87, 1086.
3. Cardellicchio, C.; Fiandanese, V.; Naso, F. G 1991, 121, 11.
4. Montanari, F. G 1956, 86, 406.
5. Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L. JCS(P1) 1985, 1115.
6. Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L. CC 1982, 647.
7. Mura, A. J.; Majetich, G.; Grieco, P. A.; Cohen, T. TL 1975, 4437.
8. Fiandanese, V.; Miccoli, G.; Naso, F.; Ronzini, L. JOM 1986, 312, 343.
9. (a) Hoshino, Y.; Ishiyama, T.; Miyaura, N.; Suzuki, A. TL 1988, 29, 3983. (b) Watanabe, T.; Miyaura, N.; Suzuki, A. JOM 1993, 444, C1.
10. Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Montanucci, M. TL 1984, 25, 4975.
11. Fiandanese, V.; Marchese, G.; Mascolo, G.; Naso, F.; Ronzini, L. TL 1988, 29, 3705.
12. Ishiyama, T.; Miyaura, N.; Suzuki, A. CL 1987, 25.
13. Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L.; Rotunno, D. TL 1989, 30, 243.
14. Florio, S.; Ronzini, L.; Sgarra, R. TL 1991, 32, 1114; 1990, 31, 2327.
15. Cardellicchio, C.; Fiandanese, V.; Naso, F. JOC 1992, 57, 1718.
16. Cardellicchio, C.; Fiandanese, V.; Naso, F.; Scilimati, A. TL 1992, 33, 5121.
17. Farina, V.; Hauck, S. I. JOC 1991, 56, 4317.
18. Babudri, F.; Fiandanese, V.; Mazzone, L.; Naso, F. TL 1994, 35, 8847.

Francesco Naso, Vito Fiandanese & Cosimo Cardellicchio

CNR, Centre MISO, University of Bari, Italy



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