Methyl a-Chloro-a-phenylthioacetate

[85920-99-6]  · C9H9ClO2S  · Methyl a-Chloro-a-phenylthioacetate  · (MW 216.70)

(an a2 carbon electrophile for the introduction of methoxycarbonylmethyl and methoxycarbonylmethylidene groups by Lewis acid-catalyzed reaction with silyl enol ethers followed by a reductive or oxidative step)

Physical Data: bp 105-107 °C/18 mmHg.1

Solubility: freely sol CH2Cl2.

Analysis of Reagent Purity: d (CDCl3) 7.47 (5H, m), 5.57 (1H, s), and 3.77 (3H, s).

Preparative Methods: by chlorination of methyl phenylthioacetate using Sulfuryl Chloride2 or N-Chlorosuccinimide (NCS):3,4 methyl phenylthioacetate (16.8 g) is stirred with powdered NCS (13.3 g) in CCl4 at rt for 10 h, the mixture filtered, the filtrate evaporated, and the residue distilled using a short Vigreux column.1

Handling, Storage, and Precautions: generally prepared shortly before use. It is stable in the absence of water, and should be kept in a stoppered flask or sealed ampule if it is not used immediately. It is an alkylating agent, and should therefore be kept in a well-ventilated hood, with skin and eyes protected while handling it.

Methyl a-chloro-a-phenylthioacetate (2) reacts with silyl enol ethers (1) in the presence of Lewis acids, typically Zinc Bromide in catalytic quantities3,4 or Titanium(IV) Chloride in stoichiometric quantities,4 to give the 1,4-dicarbonyl products (3) (eq 1). The reaction is regiospecific (eqs 2 and 3),4 and g-selective with the silyl dienol ether (4) (eq 4).3

The ZnBr2 reactions typically take 0.5-2 h at rt in CH2Cl2, and are carried out by adding the anhydrous salt to a 1:1 mixture of silyl enol ether and the chloride (1). The TiCl4 reactions are carried out similarly, and typically take 2 h at -23 °C.

The products (3) can be desulfurized with Raney Nickel to give overall the products (5) of methoxycarbonylmethylation (eq 5).3,4 They can also be oxidized using Sodium Periodate to give the corresponding sulfoxides, which undergo rapid cycloelimination when there is an appropriately placed hydrogen atom to give overall the products (6) of methoxycarbonylmethylidenation (eq 6).3,4

The homolog methyl 2-chloro-2-phenylthiopropanoate (7) can be used in similar reactions (eqs 7-9), but the oxidative desulfurization takes place towards the methyl group, giving the a-methylene ester (8) when R2 is not hydrogen (eq 9).4

The corresponding Lewis acid-catalyzed reaction of silyl enol ethers with a-chloro-a-phenylthioketones gives furans.5

Related Reagents.

Chloromethyl Phenyl Sulfide.

1. Iqbal, J. Unpublished result, Cambridge, 1982.
2. Campbell, M. M.; Jigajinni, V. B.; MacLean, K. A.; Wightman, R. H. TL 1980, 21, 3305.
3. (a) Lee, T. V.; Okonkwo, J. O. TL 1983, 24, 323. (b) Lee, T. V.; Toczek, J. JCS(P1) 1987, 759.
4. Fleming, I.; Iqbal, J. TL 1983, 24, 327.
5. Tanikaga, R.; Miyashita, K.; Sugihara, H.; Kaji, A. CC 1981, 1106.

Ian Fleming

Cambridge University, UK

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.