Palladium-katalysierte Kreuzkupplungen zu 1,2-Dialkenylcycloalkenen: Ausgangsstoffe zur Synthese vielfältiger cyclischer Kohlenstoffgerüste

Abstract

Palladium-catalyzed coupling reactions of 1,2-dibromocycloalkenes with styrene and acrylates afforded 1,6-diphenyl- and 1,6-bisalkoxycarbonyl-substituted (E,Z,E)-1,3,5-hexatrienes in high yields. The corresponding 1,6-bissilyl-compounds could be obtained from 1,2-diiodocycloalkenes and vinylsilanes. Thermal electrocyclizations of these products yielded cycloalkane-annelated cyclohexadienes with a cis relationship of the substituents from the former 1- and 6-positions of the hexatrienes due to the disrotatory ring closure. Upon photolysis no cyclization but an E-Z isomerization of an exocyclic double bond occurred. The thus formed (E,Z,Z)-1,3,5-hexatrienes underwent thermal disrotatory cyclizations to yield cyclohexadienes with a trans relationship of the substituents. Another transformation of the 1,3,5-hexatrienes is the epoxidation of their central double bond to yield 1,2-dialkenylcycloalkene oxides, which was accomplished using different oxidants. The cyclohexene- and cycloheptene-derivatives underwent Cope-rearrangements at elevated temperature to furnish 1,6-oxygen-bridged cycloalka-1,5-dienes while no reaction occurred upon heating the cyclopentene-derivatives. Apparently, a significant increase in strain occurs on going from the larger homologues to the corresponding 1,6-oxygen-bridged cyclonona-1,5-dienes. Palladium-catalyzed reductive ring openings of the epoxides yielded 1,2-dialkenylcycloalkanols with a trans relationship of the alkenyl groups. These substrates were converted to 3,4-disubstituted medium-size cycloalkenones by anionic oxy-Cope rearrangements. While the cyclononenones were exclusively formed with an (E)-configuration of the double bond and a trans relationship of the substituents and the cycloundecenones predominantly with a (Z)-configuration and a cis-relationship, the cyclodecenones could be obtained exclusively as (E)/trans-isomers or predominantly as (Z)/cis-isomers depending on the substituents and the reaction conditions. These transformations are the first examples of reversible anionic oxy-Cope rearrangements. In the twofold Heck reactions on 1,2-dibromocycloalkenes the second coupling step is generally faster than the first one. It is thus impossible to obtain unsymmetrical hexatrienes by stepwise reactions with two different alkenes. Even when using cycloalkenes with two different leaving groups, e.g. bromo and triflat substituents, the reactivity difference between the leaving groups is overcompensated by the enhanced reactivity of the intermediate bromodiene towards the Heck coupling. On the other hand, in Stille-type cross coupling reactions of these substrates with ethenyl-tri-n-butylstannane or 1-methoxyethenyl-tri-n-butylstannane only the triflate group is replaced and unsymmetrical hexatrienes were obtained after following Heck reactions with acrylates. This Stille-Heck sequence could be performed as a one-pot procedure. The products of Stille couplings with the methoxyethenylstannane were converted to bicyclo[4.4.0]decenones via electrocyclization and hydrolysis of the enol ether-moiety and to bicyclo[4.3.0]nonenones via hydrolysis and Michael addition. These bicycloalkenones yielded cyclodecynones and cyclononynones upon epoxidation of their double bond and following Eschenmoser fragmentation. Thus, 1,2-dialkenylcycloalkenes are valuable starting materials for the formation of interesting mono- and polycyclic carbon skeletons.