Premium
Process‐Scale Total Synthesis of Nature‐Identical (−)‐( S , S )‐7‐Hydroxycalamenal in High Enantiomeric Purity through Catalytic Enantioselective Hydrogenation
Author(s) -
Benincori Tiziana,
Bruno Silvana,
Celentano Giuseppe,
Pilati Tullio,
Ponti Alessandro,
Rizzo Simona,
Sada Mara,
Sannicolò Francesco
Publication year - 2005
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.200590139
Subject(s) - chemistry , enantioselective synthesis , enantiomer , enantiomeric excess , catalysis , stereoselectivity , asymmetric hydrogenation , catalytic hydrogenation , naphthalene , stereochemistry , transfer hydrogenation , organic chemistry , medicinal chemistry , combinatorial chemistry , ruthenium
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.