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Ring‐Closing Strategy Utilizing Nitrile α‐Anions: Chiral Synthesis of (+)‐Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)‐Grandisol
Author(s) -
Fujiwara Tetsuya,
Okabayashi Tomohito,
Takahama Yuji,
Matsuo Noritada,
Tanabe Yoo
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801160
Subject(s) - chemistry , nitrile , cyclopropane , total synthesis , stereochemistry , enantioselective synthesis , cyclobutane , epoxide , ketone , chiral auxiliary , ring (chemistry) , organic chemistry , catalysis
Chiral syntheses of two distinct small cycloalkanes, (1 R ,3 R )‐(1 Z )‐norchrysanthemic acid and (+)‐grandisol, were performed by characteristic ring‐closing methodologies using carbanions at the α‐position of nitriles (nitrile α‐anions). (i) (1 R ,3 R )‐(1 Z )‐Norchrysanthemic acid, a highly potent ingredient of synthetic pyrethroid containing a cyclopropane structure, was synthesized from readily available ( S )‐epoxide derived from 3‐methyl‐but‐2‐en‐1‐ol in 7 steps in 23 % overall yield and with > 98 % ee . This sequence involves a trans ‐selective cyclopropane formation using the nitrile α‐anion of ( S )‐3‐mesyloxynitrile as the key step. The present chiral synthesis was performed with effective stereocontrol of both the chirality in the 1,3‐positions on the cyclopropane and the Z ‐geometry of the propenyl group. (ii) (+)‐Grandisol, an insect sex pheromone possessing a characteristic cyclobutane structure, was synthesized from commercially available cyclopropyl methyl ketone (route A) or from commercially available 3‐cyanopropylzinc bromide and 1‐bromo‐1‐methylpropene (route B) in 10 or 8 steps in 6 % or 8 % overall yield and with 80 % ee . This sequence involves a Shi asymmetric epoxidation of a trisubstituted olefin and a straightforward Stork‐type asymmetric cyclobutane formation with clean S N 2 stereoinversion using the nitrile α‐anion of the chiral epoxynitrile. The present expedient method is the second asymmetric total synthesis starting from achiral compounds.