Intramolecular Pauson-Khand Reactions of Methylenecyclopropane and Bicyclopropylidene Derivatives as an Approach to Spiro(cyclopropanebicyclo[n.3.0]alkenones)

The trimethylsilyl‐protected enynes 9 a–c and 14 a, b with alkynyl substituents on the three‐membered ring or on the double bond of a methylenecyclopropane or a bicyclopropylidene moiety were prepared in two steps from the alcohols 6 a–c and 12 a, b, respectively, by conversion to the iodides and their coupling with lithium (trimethylsilyl)acetylide (8) in 38–73 % overall yields. The bicyclopropylidene derivative 9 d was synthesized in 49 % yield directly from bicyclopropylidene (3) by lithiation followed by coupling with (5‐iodopent‐1‐ynyl)trimethylsilane (11). Enynes 9 b–d were protiodesilylated by treatment with K2CO3 in methanol to give the corresponding unprotected enynes 10 b–d in 53, 74 and 94 % yield, respectively. Enynes 17 a–c with a carbonyl group adjacent to the acetylenic moiety were synthesized from oxo derivatives 15 a–c by Wittig olefination followed by coupling with 8 in 47, 18 and 12 % overall yield, respectively. Pauson–Khand reactions of the methylenecyclopropane derivatives with a substituent on the ring (9 a,b and 10 a) as well as on the double bond (14 a,b and their in situ prepared protiodesilylated analogues) proceeded smoothly by stirring of the corresponding enyne with [Co2(CO)8] in dichloromethane at ambient temperature followed by treatment of the formed complexes with trimethylamine N‐oxide under an oxygen atmosphere at −78 °C to give tricyclic or spirocyclopropanated bicyclic enones 18 a, b, 19 a, 20 a, b, 21 a, b in good yields. Alkynylbicyclopropylidene derivatives 9 c, d and 10 c, d formed the corresponding cobalt complexes at −78 to −20 °C. Treatment of the latter with N‐methylmorpholine N‐oxide under an argon atmosphere at −20 °C gave the spirocyclopropanated tricyclic enones 18 c, 19 c and 18 d in 31–45 % yields. The structure of 19 c was proved by X‐ray crystal structure analysis. The cyclization of enynones 17 a–c in MeCN at 80 °C gave the spirocyclopropanated bicyclic diketones 22 a–c in 38–65 % yields. Intramolecular PKRs of the enynes 25 a, d with a chiral auxiliary adjacent to the triple bond gave the corresponding products 26 a, d in 70 and 79 % yield, respectively, as 5:1 and 8:1 mixtures of diastereomers, respectively. Addition of lithium dimethylcuprate or higher order cuprates to the double bond of the former furnished bridgehead‐substituted bicyclo[3.3.0]octanones 27 a–c in 57–86% yields. Protiodesilylation of 27 a followed by acetal cleavage gave the enantiomerically pure spirocyclopropanated bicyclo[3.3.0]