Carbon atom insertion bicycloannulation: total syntheses of ishwarane and ishwarone

Abstract

. Can. J. Chem. 62, 1908Chem. 62, (1984. insertion of a carbon atom into a methyl cyclohexene, leading in a single synthetic step to a bicyclo[3.2. I .02.']octane by carbene addition to the double bond and carbene insertion into a methyl C-H bond, has been accomplished by treating the cyclohexene with carbon tetrabromide and methyllithium at low temperatures. This new bicycloannulation method has been employed in a total synthesis of ishwarane (I), the naturally occurring parent hydrocarbon of the ishwarane class of tetracyclic sesquiterpenes. Although this reaction was not successful with various possible precursors of ishwarone (2), this natural product was prepared in low yield by a two-step version of the carbon atom insertion bicycloannulation (CAiB) procedure involving addition of bromoform-derived dibromocarbene to the octalone (5) followed by treatment of the resulting dibromocyclopropane (56) with methyllithiurn. The same two-step sequence was also successful in the first synthesis of norishwarane (20), the hydrocarbon comprising the bare ring system of the ishwarane sesquiterpenoids. The Diels-Alder synthesis used in the preparation of the octalin precursor (18) of norishwarane could not be used for the terpenes themselves because of the lack of dienophilic reactivity of the required cyclohexenone (7). A regioselective Diels-Alder equivalent sequence was therefore developed, consisting of conjugate addition of lithium di(3-methyl-3-buteny1)cuprate (42) to 2,3,4-trimethylcyclohex-Zen-I-one (7), epoxidation, base-catalyzed cyclization of the resulting epoxide (47) to a mixture of primary and tertiary alcohols (50 and 49, respectively), and dehydration of 49 to give 5. In the case of ishwarane, the octalin precursor (62) was synthesized by conjugate addition of lithium dimethylcuprate to octalone 59, addition of methyl magnesium bromide to the resulting decalone (60) to give octalol 61, and dehydration. Chem. 62, 1908Chem. 62, (1984.En faisant rkagir le cyclohexkne avec le titrabromure de carbone et le mCthyllithium a basse tempkrature, on a rtalisC I'insertion d'un atome de carbone dans le mCthylcyclohexkne; on a ainsi obtenu en une seule Ctape le bicyclo[3.2.1 .02.']octane par I'addition de carbene sur la double liaison et par une insertion de carbkne dans une liaison C-H du mithyle. OR a utilisee cette nouvelle methode de bicycloannellation dans une synthttse totale de I'ishwarane (I), I'hydrocarbure naturel parent des sesquiterpknes tetracycliques de la classe de I'ishwarane. Bien que cette reaction n'aie pas pu &tre appliquCe avec succes i divers precurseurs possibles de I'ishwarone (2), on a prepare ce produit naturel avec un faible rendement en faisant appel a une version en deux Ctapes de la mtthode de bicycloannellation par insertion d'un atome de carbone (BIAC) impliquant une addition d'un dibromocarbkne, provenant du bromoforme, sur I'octalone (51, puis une reaction du dibromocyclopropane (56) qui en rtsulte avec du mCthyllithium. On a aussi utilist cette mCthode avec succks pour realiser ...

Total Synthesis of (−)-Ascochlorin via a Cyclobutenone-Based Benzannulation Strategy

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CH Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals

“…The insertion reaction on carbene 283 indeed provided ishwarane ( 284 ) in 26 % yield, successfully providing a new form of “chemical logic” in natural product synthesis. Seven years later, the Cory research group also accomplished the total synthesis of ishwarone, a more oxidized version of 284 143b…”

Synthesis of a Highly Hindered Hydrindanone via α-Carbonyl Radical Cyclization: Enantiospecific Formal Syntheses of (−)-Pinguisenol and (−)-α-Pinguisene

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