2-Cyclohexenone asymmetric reduction

In general, structural variations to the backbone of the Chirald ligand have not led to the development of more selective or reliable LAH complexes for use in asymmetric reductions. Other complexes of amino alcohols with LAH have been studied for their ability to achieve enantioselective reduction of prochiral ketones. However, in most cases the selectivities observed have been moderate. The complex of LAH with the amino alcohol (IS) reduces some enones, such as cyclohexenone and cyclopentenone, to the corresponding (5)-alcohols in high optical purities (100% and 82% ee, respectively). ... 

The pyridyl analog (51) leads to the opposite asymmetric orientation in most cases. Asymmetric reduction of 2-cyclohexenone affords (/ )-2-cyclohexenol with 98% ee. Other cyclic ketones are also converted to (f )-carbinols in high optical yields (Scheme 9), but the reduction of acyclic ketones is only moderately stereoselective. ... 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

New and continuing efforts towards the total synthesis of dendrobine (59 R = H) have been reported.In one sequence (Scheme 8), the butyric acid (85) was readily transformed into the ketal (86), which was submitted to a Birch reduction and hydrolysis to yield the cyclohexenone (87) as the single diastereomeric product. Acid treatment of (87) gave a stereoisomeric mixture of products (88) which were not separated but subjected to reaction with base to give compound (89). The same compound was obtained directly by treatment of (87) with strong base (Michael and aldol condensations combined). After some discouraging results, the tricyclic compound (89) was transformed into the desired keto-acid (90) via an abnormal ozonolysis reaction. Compound (90) possesses the correct stereochemistry at three asymmetric centres required for elaboration of dendrobine (59 R = H). 

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