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Analogues of α ‐Campholenal (= (1 R )‐2,2,3‐Trimethylcyclopent‐3‐ene‐1‐acetaldehyde) as Building Blocks for (+)‐ β ‐Necrodol (= (1 S ,3 S )‐2,2,3‐Trimethyl‐4‐methylenecyclopentanemethanol) and Sandalwood‐like Alcohols
Author(s) -
Chapuis Christian,
Barthe Michel,
Cantatore Carole,
SaintLéger Christine,
Wyss Patrick
Publication year - 2006
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.200690236
Subject(s) - chemistry , acetaldehyde , acetal , ketone , dimethyldioxirane , isomerization , aldehyde , stereoselectivity , alcohol , double bond , moiety , ene reaction , stereochemistry , epoxide , organic chemistry , allyl alcohol , ethanol , catalysis
To complete our panorama in structure–activity relationships (SARs) of sandalwood‐like alcohols derived from analogues of α ‐campholenal (= (1 R )‐2,2,3‐trimethylcyclopent‐3‐ene‐1‐acetaldehyde), we isomerized the epoxy‐isopropyl‐apopinene (−)‐ 2d to the corresponding unreported α ‐campholenal analogue (+)‐ 4d ( Scheme 1). Derived from the known 3‐demethyl‐ α ‐campholenal (+)‐ 4a , we prepared the saturated analogue (+)‐ 5a by hydrogenation, while the heterocyclic aldehyde (+)‐ 5b was obtained via a Bayer‐Villiger reaction from the known methyl ketone (+)‐ 6 . Oxidative hydroboration of the known α ‐campholenal acetal (−)‐ 8b allowed, after subsequent oxidation of alcohol (+)‐ 9b to ketone (+)‐ 10 , and appropriate alkyl Grignard reaction, access to the 3,4‐disubstituted analogues (+)‐ 4f,g following dehydration and deprotection. ( Scheme 2). Epoxidation of either (+)‐ 4b or its methyl ketone (+)‐ 4h , afforded stereoselectively the trans ‐epoxy derivatives 11a,b , while the minor cis ‐stereoisomer (+)‐ 12a was isolated by chromatography ( trans/cis of the epoxy moiety relative to the C 2 or C 3 side chain). Alternatively, the corresponding trans ‐epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans ‐epoxy aldehyde (+)‐ 11a or by stereoselective epoxidation of the α ‐campholenol (+)‐ 15a or of its acetate (−)‐ 15b , respectively. Their cis ‐analogues were prepared starting from (+)‐ 12a . Either (+)‐ 4h or (−)‐ 11b , was submitted to a Bayer‐Villiger oxidation to afford acetate (−)‐ 16a . Since isomerizations of (−)‐ 16 lead preferentially to β ‐campholene isomers, we followed a known procedure for the isomerization of (−)‐epoxyverbenone (−)‐ 2e to the norcampholenal analogue (+)‐ 19a . Reduction and subsequent protection afforded the silyl ether (−)‐ 19c , which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)‐ 20c . Further oxidation and epimerization furnished the trans ‐ketone (−)‐ 17a , a known intermediate of either (+)‐ β ‐necrodol (= (+)‐(1 S ,3 S )‐2,2,3‐trimethyl‐4‐methylenecyclopentanemethanol; 17c ) or (+)‐( Z )‐lancifolol (= (1 S ,3 R ,4 Z )‐2,2,3‐trimethyl‐4‐(4‐methylpent‐3‐enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)‐ 4b gave the saturated cis ‐aldehyde (+)‐ 21 , readily reduced to its corresponding alcohol (+)‐ 22a . Similarly, hydrogenation of β ‐campholenol (= 2,3,3‐trimethylcyclopent‐1‐ene‐1‐ethanol) gave access via the cis ‐alcohol rac ‐ 23a , to the cis ‐aldehyde rac ‐ 24 .