Formale Totalsynthese von (±)‐Isocomen durch Anwendung der α‐Alkinon‐Cyclisierung

Abstract

Formal Total Synthesis of (&)-Isacornen by Application of the a-Alkinon CyclizationA total synthesis of the racemic form of the sesquiterpene isocomene (A) was accomplished by application of the cyclopentenone anellation B+D (Scheme 1 ) which includes the a-alkynone cyclization C-D, a gas-phase flow thermolytic process. Starting with the known product 2 (Scheme 3 ) of the anellation B+D, the elaboration of ring C of A proceeded in 9 steps to the a-alkynone 16 (Scheme 5 ) which was cyclized at 540" selectively to give the angularly fused triquinane 4 (77%). A two-step procedure then led to 5 (Scheme 6). a last but one intermediate in a known total synthesis of (+)-A. The conversion of 16 to 4 also demonstrated the compatibility of an acetoxy function with the anellation sequence B+D.

Transition metal-mediated routes to cyclopentenones

“…The intramolecular formation of a new carbon-carbon bond between an acetylenic (b-position) and a non-activated carbon atom (b 0 -position) is accompanied by a [1,2]-migration of the hydrogen at the b-position to the a-position. The alkynone cyclisation offers a route to the preparation of monocyclic, bicyclic and spiro compounds containing a cyclopentenone unit [23].…”

Synthesis of Polyquinane Natural Products: An Update

“…Understandably, their synthesis has aroused considerable interest. 180 Dreiding and co-workers 181 have applied their R-alkynone cyclization strategy toward a formal synthesis of (()-isocomene (348) (Scheme 86). Previ-ously synthesized 182 diquinane enone 350 was elaborated into the R-alkynone 351, which on flash vacuum pyrolysis furnished the angular triquinane 352, an advanced intermediate in Paquette's 180c,g synthesis of (()-348.…”

The Asymmetric Synthesis of Fused Cyclopentenone Ring Systems: A formal asymmetric total synthesis of (−)‐isocomene

“…The latter have been prepared in racemic form using various synthetic routes. Interestingly, racemic 69 has been employed for the stereoselective preparation of (&)-isocomene ((*)-16) by Dreiding and coworkers [22], thus making the enantiospecific preparation of (+)-69 a formal asymmetric total synthesis of (-)-isocomene ((-)-16). Further application of the chiral bicyclic lactam methodology towards natural and unnatural C-frameworks are currently underway and will be reported in the future.…”

“…The assignments are additionally supported for some compounds by NOE experiments (see Exper. Part) and, for the known compound 68 [20] [21], 69 [22], and 79 [23], by comparison of the spectra with reported data. The latter have been prepared in racemic form using various synthetic routes.…”