Steric effects in the diastereoselective reduction of β-ketosulfones

Abstract

. Can. J. Chem. 66, 2860 (1988).The stereochemical course of the reduction of ketones adjacent to a chiral center normally shows some diastereoselectivity (described by Cram's rule), the degree of which is dependent on the structure of the ketone and on the reaction conditions; the selectivity in acyclic species is often not very great. In this paper, we describe the sodium borohydride reduction of four acyclic P-ketosulfones, containing a chiral center at the a position, in which the products are formed with high diastereoselectivity. Reasons for this selectivity became apparent when we were able to show that these ketosulfones apparently exist predominantly in the same conformation in solution as in the solid state. This conformation requires that the preferred trajectory for nucleophilic attack on the carbonyl group leads to reaction on the re face, to yield the threo diastereomer of the P-hydroxysulfone. ' The results that led to these conclusions were obtained from structural studies by X-ray crystallography, as well as by detailed 'H and 13C nuclear magnetic resonance spectroscopy. In some cases, the latter spectra were run both in solution and in the solid state. 66, 2860 (1988).La degrC de diastCrCosClectivitC (dCcrit par la rtgle de Cram) de la rCduction de cCtones adjacentes d'un centre chiral dCpend de la structure de la cCtone ainsi que des conditions de la rCaction; la sClectivitC des esptces acycliques est souvent faible. Dans ce travail, on dCcrit la rkduction par le borohydrure de sodium de quatre P-~Ctosulfones acycliques, contenant un centre chiral en position a, qui donnent lieu i une haute diastCrCosClectivitC. Les raisons de cette sClectivit6 sont devenues apparentes lorsqu'on a pu montrer que la conformation principale de ces ~Ctosulfones est la mCme i 1'Ctat solide qu'en solution. Cette conformation implique que l'attaque nuclCophile sur le groupement carbonyle se produit prCfCrentiellement selon une trajectoire d'attaque sur la face re qui conduit au diastCrCoisomtre thrio de la P-hydroxysulfone. Les rksultats qui ont permis de proposercette conclusion ont Ct C obtenus i l'aide d'Ctudes de structures par diffraction des rayons-X ainsi que par resonance magnCtique nuclCaire du 'H et du 13C. Dans quelques cas, on a dCterminC ces derniers spectres tant en solution qu'i 1'Ctat solide.[Traduit par la revue]

Stereochemical studies on the formation of α,β-epoxysulfones using α-chloro-β-hydroxysulfones of known configuration

“…Thus Bohlmann's diastereomeric mixture of chlorohydrins 1 and 2 (23) was prepared by a different reaction sequence, as outlined in Scheme 1. The reactions used in this synthesis are directly analogous to those described in the previous paper (27). Treatment of these molecules with potassium tert-butoxide in DMF solution gave an oily mixture from which the E-epoxysulfone, 3, could be recovered.…”

“…We had prepared the threo chlorohydrin, 6, and had established its stereochemistry unequivocally (27). When this was subjected to the same basic An epoxide with this stereochemistry could not have been forrned directly from 6 by a reaction pathway involving the normal stereoelectronics expected for the conversion of a chlorohydrin into an epoxide (28).…”

“…We reasoned that this cleavage reaction could perhaps be disfavoured by employing an alkylsulfonyl residue in place of the phenylsulfonyl moiety (29), and proceeded to explore the chemistry of the equivalent compounds leading to 7 and 15, but instead incorporating the P a reasontert-butylsulfonyl group. This was chosen to provid, able degree of steric hindrance around the sulfonyl group so as to afford adequate diastereoselectivity in the reduction of the appropriate P-ketosulfones (27).…”

“…This could be chlorinated in the usual way to 17, which on reduction with sodium borohydride gave the chlorohydrin 18 as a mixture of diastereomers, the threo form, 18a, again being predominant. The corresponding ethyl derivative, 19, was also prepared (27), again as a mixture of diastereomers. When 18 and 19 were subjected to the regular basic conditions used for epoxide formation, the epoxysulfones 20 and 21, respectively, were cleanly formed, as outlined in e q P I .…”

“…We have demonstrated that it is possible to prepare highly substituted a-chloro-P-hydroxysulfones (27) of known stereochemistry. The purpose of the work described here was to take these and other chlorohydrins and convert them into a,Pepoxysulfones, at the same time determining unambiguously the stereochemistry of the relevant species by the use of 'H nmr spectroscopy and X-ray crystallography.…”