Hydroxythiols—

Scheme 10.62 Borane reduction of acetophenone with 1,2- and 1,3-hydroxythiol ligands.

Dioxa-, 1,3,2-dithia-, and 1,3,2-oxathiaborolanes 322 can be readily prepared by reaction of bis(diisopropyl-amino)borylacetylenes 320 with the appropriate diol, dithiol, or hydroxythiol (321 X = 0, S) in the presence of 2 equiv of HC1 (Equation 12) <2004EJI4223>. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

The diastereomerically pure camphor-based 1,3-oxathiane 36, formed by the reaction of a,(S-unsaturated aldehydes with the hydroxythiol 37, undergoes a stereospecific ketene Claisen rearrangement with dichloroketene to give the stereo-pure 10-membeted thiolactone <02CC2534>. 

Synthesis of carbinols and (Scheme 9) is entirely analogous to the syntheses described earlier. However cleavage in the case of and was carried out by mecuis of N-chloro-succinimide (NCS) - silver nitrate (25). This cleavage produces not only the chiral a-hydroxyaldehydes in good yields but also returns the hydroxythiol chiral adjuvcuit in form of the pair of diastereomeric sultines (Lithiimi aluminum hydride reduction... 

The conversion of a frons-diol system (106, Z = Y = OH) to a cis-hydroxythiol (109, X = SH, Y = OH), through thiourethan derivatives, has been achieved with the model compound [Pg.186]

When 4 is treated with excess phenylmagnesium bromide, good to excellent yields of trans-4,5-bis(hydroxydiphenylmethyl)-2,2-dimethyl-l,3-dioxacyclopentane (21) are produced. This has been used as an effective optical resolution agent for bicyclic enones [16], and for the preparation of the hydroxythiol 22, which was transformed into the 1,3-oxathiepane 23 [17] (Scheme 5). 

From the standpoint of organic chemistry hydrogen sulfide can add to double bonds, form hydroxythiols with epoxides and olthiols with aldehydes. 

A variety of 9-ketals were prepared from either methyl ester 245 (obtained from I-PGA2 diester 21 by hydrogenation followe3 by selective hydrolysis) or acid 2, by the usual ketalization techniques involving treatment of the ketone with an excess of the requisite diol, dithiol or hydroxythiol in the presence of an acid catalyst (109). Saponification of the ester afforded the corresponding acids listed in Table IV. [A recent report from the Upjohn laboratories describes the facile preparation of the ethylene ketal of PGE2 (110). 1... 

This selectivity is subject to a strong solvent effect, and is probably determined by the polarity and solubihty of the substrates. The least soluble thiol usually adsorbs preferentially. Thus, in a mixture of an alkanethiol and an from ethanol solution. Adsorption from acetonitrile, on the other hand, does not show any preference, and adsorption from isooctane results in the preferential adsorption of a hydroxythiol . The preference of long-chain thiols over the short-chain ones and compounds with bulky substituents also depends on the solvent, being much less pronounced in non-polar solvents. Adsorption of octadecanethiol is preferred over adsorption of r-butylthiol in isooctane solution by a factor of only 40-100 (the corresponding ratio in ethanol is 290-710, vide supra), and by just a factor of 3-4 over adsorption of straight-chain butanethiol (compared with a 20-30 ratio for C22 vs C12 preference in ethanol, vide suprd). ... 

Table II. Isolated Yields of Aldehydes and Hydroxythiol from Deprotection of Oxathiane Derivatives...

N-Methy Ipyrrolidinelmagnesium nitrate a-Hydroxythiolic acid esters from l-hydroxy-2-ketothioethers... 

Lactones from hydroxythiolic acid esters Macrocyclic lactones... 

Chiral y-alkoxy-p-hydroxythiolic acid esters CO - C(OH)C — COSR... 

Glycidic from a-bromo-p-hydroxythiolic acid esters... 

A soln. of /er/-butyl bromothioacetate in dichloromethane at —78° treated via syringe with 1.1 eqs. dicyclopentylborinyl triflate in the same solvent followed by 1.2 eqs. of /-Pr2NEt, stirred at —78° for 30 min, a soln. of 2,3-dimethoxybenzaldehyde in dichloromethane added slowly, stirred for a further 2 h at the same temp., 1.2 eqs. /-Pr2NEt added, the mixture warmed to room temp., and stirred for 12 h - / r/-butyl (2R, 3S )-2,3-epoxy-3-(2,3-dimethoxyphenyl)thiopropanoate. Y 62%. This method gives higher /ra 5-selectivity than the classical Darzens glycidic ester condensation. F.e. and isolation of the intermediate a-bromo-P-hydroxythiolic acid esters, also conversion to glycidic acid esters (with Mg(OMe)2) s. R.P. Polniaszek, S.E. Belmont, Synth. Commun. 19, 221-32 (1989). 

Stannous triflate I tri-n-butyltin fluoride j chiral diamine p-Hydroxythiolic acid esters from O-silylketene 0,S-acetals and aldehydes Asym. aldol-type condensation... 

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