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Über die Stereoselektivität der α‐Alkylierung von (1 R , 2 S ) (+)‐ cis ‐2‐hydroxy‐cyclohexancarbonsäureäthylester
Author(s) -
Fráter György
Publication year - 1980
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19800630605
Subject(s) - chemistry , alkylation , stereoselectivity , yield (engineering) , reagent , enantiomeric excess , cyclohexane , enantiomer , stereochemistry , medicinal chemistry , enantioselective synthesis , organic chemistry , catalysis , metallurgy , materials science
The Stereoselectivity of the α‐Alkylation of (+)‐(1 R , 2 S )‐ cis ‐Ethyl‐2‐hydroxy‐cyclohexanecarboxylate In continuation of our work on the stereoselectivity of the α‐alkylation of β‐hydroxyesters [1] [2], we studied this reaction with the title compound (+)‐ 2 . The latter was prepared through reduction of 1 with baker's yeast. Alkylation of the dianion of (+)‐ 2 furnished (−)‐ 4 in 72% chemical yield (Scheme 1) and with a stereoselectivity of 95%. Analogously, (−)‐ 7 was prepared with similar yields. Oxidation of (−)‐ 4 and (−)‐ 7 respectively furnished the ketones (−)‐ 6 (Scheme 3) and (−)‐ 8 (Scheme 4) respectively, each with about 76% enantiomeric excess (NMR.). It is noteworthy that yeast reduction of rac ‐ 6 (Scheme 3) is completely enantioselective with respect to substrate and product and gives optically pure (−)‐ 4 in 10% yield, which was converted into optically pure (−)‐ 6 (Scheme 3) . The alkylation of the dianionic intermediate shows a higher stereoselectivity (95%) from the pseudoequatorial side than that of 1‐acetyl‐ or 1‐cyano‐4‐ t ‐butyl‐cyclohexane (71% and 85%) [9] or that of ethyl 2‐methyl‐cyclohexanecarboxylate (82%). The stereochemical outcome of the above alkylation is comparable with that found in open chain examples [1] [2]. Finally (+)‐(1 R , 2 S )‐ 2 was also alkylated with Wichterle's reagent to give (−)‐(1 S , 2 S )‐ 9 in 64% yield. The latter was transformed into (−)‐( S )‐ 10 and further into (−)‐( S )‐ 11 (Scheme 5) . (−)‐( S )‐ 10 and (−)‐( S )‐ 11 showed an e.e. of 76–78% (see also [11]). Comparison of these results with those in [11] confirmed our former stereochemical assignment concerning the alkylation step.