ChemInform Abstract: Mono‐ and Dialkylation of Derivatives of (1R,2S)‐2‐Hydroxycyclopentanecarboxylic Acid and ‐cyclohexanecarboxylic Acid via Bicyclic Dioxanones: Selective Generation of Three Contiguous Stereogenic Centers on a Cyclohexane Ring.

Abstract

Dedicated to Dr. Gunther Ohloffon the occasion of his 65th birthday (1 3.111.89) Ethyl (1 R,2S)-2-hydroxycyclopentanecarboxylate and -cyclohexanecarboxylate ( l a and 2a, respectively) obtained in 40 and 70 % yield by reduction of 3-oxocyclopentanecarboxylate and cyclohexanecarboxylate, respectively (Scheme Z), with non-fermenting yeast, are converted to bicyclic dioxanone derivatives 3 and 4 with formaldehyde, isobutyraldehyde, and pivalaldehyde (Scheme 3 ) . The Li-enolates of these dioxanones are alkylated (+5a-5i, 5j, 6adg), hydroxyalkylated (+ 51,m, 6d,e), acylated (+ Sk, 6c) and phenylselenenylated (+7-9) with usually high yields and excellent diastereoselectivities (Scheme 3, Tables 1 and 2). All the major isomers formed under kinetic control are shown to have cis-fused bicyclic structures. Oxidation of the seleno compounds 7-9 leads to a,p-unsaturated carbonyl derivatives 10-13 (Scheme 3) of which the products 12a-c with the C=C bond in the carbocyclic ring (exocyclic on the dioxanone ring) are most readily isolated (70-80% from the saturated precursors). Michael addition of Cu(1)-containing reagents to 12a+ and subsequent alkylations afford dioxanones 14a-i and 1 6 a 4 with trans-fused cyclohexane ring (Scheme 4 ) . All enolate alkylations are carried out in the presence of the cyclic urea DMPU as a cosolvent. The configuration of the products is established by NMR measurements and chemical correlation. Some of the products are converted to single isomers of monocyclic hydroxycyclopentane (17-19) and cyclohexane derivatives (20-23; Scheme 5). Possible uses of the described reactions for EPC synthesis are outlined. The observed steric course of the reactions is discussed and compared with that of analogous transformations of monocyclic and acyclic derivatives.