Radikalische Cyclisierung von Dienen, V. Substratkontrollierte asymmetrische Synthese von (−)‐Hirsuten und (−)‐3‐Hydroxyhirsuten aus (R)‐(−)‐Carvon

Abstract

Radical‐Type Cyclization of Dienes, V. – Substrate‐Controlled Asymmetric Synthesis of (−)‐Hirsutene and (−)‐3‐Hydroxyhirsutene from (R)‐(−)‐Carvone (3aR,6aR)‐(−)‐6a‐Methyl‐3,3a,4,6a‐tetrahydro‐2H‐cyclopenta‐ [b]furan‐2‐one (6) and (1R,4S)‐(−)‐3‐[4‐(but‐3‐inyl)‐3‐methyl‐cyclopent‐2‐enyl]‐2,2‐dimethylpropan‐1‐ol (11) are key compounds in the synthesis reported in this paper. Enantiomerically pure 6 was obtained in five straightforward steps from the inexpensive precursor (R)‐(−)‐carvone (1). Compound 11 was prepared from 6 via an SN2′ reaction, by analogy with the synthesis reported by Curran et al. The linear triquinanes 13 and 15 were obtained in gram quantities in two additional steps. The utilisation of (S)‐(+)‐carvone (ent‐1) allows access to the other enantiomeric forms. X‐ray analysis of 15a confirmed the structure of 15 and, by correlation, that of 13.

Synthesis and rearrangement of [1,1′-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols: a general access to bicyclo[3.3.0]octenes (hexahydropentalenes)

“…For the mechanism of the rearrangement of 37, we refer to a closely related example. 24 From a synthetic point of view it is interesting to note that 42, 45 and 46 represent partial structures of the linear triquinanes endo-hirsutene (47), 29 endo-capnellene (48) 30 and both ceratopicanol (49) 31 and cucumin-H (50), 27,32 respectively (Scheme 8). While examples for successful syntheses of angular triquinanes via cyclobutylmethyl to cyclopentyl rearrangements are known, 33 their potential for a synthesis of linear triquinanes remains to be explored.…”

Synthesis of Polyquinane Natural Products: An Update

“…Weinges and co-workers 124 have developed a synthesis of (-)-hirsutene (209) starting from (R)-carvone (Scheme 56). Oxymercuration and radical cyclization reactions transformed (R)-carvone into the bicyclo[3.2.1]octanone 245, which through a series of reactions was converted into the lactone 246, an intermediate in the Curran's 107u synthesis of (()hirsutene (209).…”

Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

“…More recently, 164 an elegant asymmetric synthesis of (-)-hirsutene and (-)-3-hydroxyhirsutene involving the formation and the selective transformation of a chiral bicyclo[3.2.1]octanone was reported. Acetoxymercuration-demercuration of (R)-(-)-carvone (287) proceeds by a radical tandem cyclization to form 288 in 35% yield.…”

“…More recently, 164 an elegant asymmetric synthesis of (-)-hirsutene and (-)-3-hydroxyhirsutene from chiral bicyclo[3.2.1]octanone 288 was reported. Hydroxy ketone 288, easily obtained from (R)-(-)carvone is oxidatively rearranged to (+)-bicyclic lactone 601 precursor of the natural products by using standard modifications.…”