Process-Scale Total Synthesis of Nature-Identical (−)-(S,S)-7-Hydroxycalamenal in High Enantiomeric Purity through Catalytic Enantioselective Hydrogenation
✍ Scribed by Tiziana Benincori; Silvana Bruno; Giuseppe Celentano; Tullio Pilati; Alessandro Ponti; Simona Rizzo; Mara Sada; Francesco Sannicolò
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- German
- Weight
- 266 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
A process‐scale stereoselective synthesis of nature‐identical (−)‐(S,S)‐7‐hydroxycalamenal (=(−)‐(5__S__,8__S__)‐5,6,7,8‐tetrahydro‐3‐hydroxy‐5‐methyl‐8‐(1‐methylethyl)naphthalene‐2‐carbaldehyde; (−)‐1a) in 96% enantiomeric excess (ee) with the aid of chiral Ru complexes has been developed. The key step was the enantioselective hydrogenation of easily accessible 2‐(4‐methoxyphenyl)‐3‐methylbut‐2‐enoic acid (10) to (+)‐11 in a 86% ee (Scheme 5 and Table 1). A substantial increase in optical purity (96% ee) was achieved by induced crystallization of the intermediate (+)‐3,4‐dihydro‐4‐(1‐methylethyl)‐7‐methoxy‐2__H__‐naphthalen‐1‐one ((+)‐3). Computational conformation analysis carried out on the analog (−)‐9 rationalized the high diastereoselectivity achieved in the catalytic hydrogenation of the CC bond.