Dibenzocyclooctadiene synthesis

A recent endeavor at the total synthesis of isopavines describes a promising novel route to these bases via functionalized dibenzocyclooctadienes (Scheme 27) 148). Dibenzocyclooctadienyl ether 132, formed from homoveratraldehyde (131) by a double Friedel-Crafts alkylation, is converted to dibenzocyclooc-tatrienol 133. Treatment with hydrazoic acid, followed by thermolysis and reduction, supplies ( )-isopavine (35) in good overall yield (53%). Subsequent attempts to prepare pavine bases by this approach have proved to be unsuccessful 148). 

The application of the Ullmann coupling to the synthesis of dibenzocyclooctadiene lignans was described in the late 1970 s by the groups of Ziegler and of Brown and Robin. 

SCHEME 93. Synthesis of dibenzocyclooctadiene-type neolignans and spirodienones... 

All of the routes described so far can be readily adapted to provide asymmetric syntheses of lignans. Thus, Koga et al. have synthesised (+)-yatein (36) and (+)-/rfl/j5-burseran (37) by conjugate addition to a chiral butenolide (35) (scheme 8) [54,55]. The more readily available menthyloxybutenolide (38) has been utilised by other groups [56,57]. The products (39) and (40) after desulfurisation, serve as precursors for the synthesis of dibenzocyclooctadienes, furofurans and aryltetralins (scheme... 

This reaction was a key step in the synthesis of the (+)-form of the dibenzocyclooctadiene lignan lactone steganacin (5).°... 

The versatility of the Meyers reaction for the construction of the dibenzocyclooctadiene backbone is amply documented (Fig. 8.2). In particular, lignans (-)-interiotherin A (17) [21], (-)-schizandrin (18), (-)-isoschizandrin (19) [22], and (-)-gomisin E (20) [21] were prepared by this method. The synthetic utility of the Meyers reaction to create the axially chiral biaryl skeletal framework was further displayed by the atroposelective syntheses of natural naphthylisoquinoline alkaloids including (-)-O-methylancistrocladine (21) [23] and (-)-0-methylhamatine (22) [24], among others [25, 26], and by the synthesis of enantiomericaUy pure C -symmetric biphenyl ligand 23 and binaphthyl porphyrin 24 (Fig. 8.3), which have been used as intermediates for the preparation of chiral catalysts for asymmetric reduction and epoxidation [27, 28]. 

Molander s research group employed an 8-endo-trig car-bonyl-alkene cyclization for the final step of their total synthesis of isoschizandrin, a dibenzocyclooctadiene lignan isolated from the fruit of Schizandra chinesis, a creeping vine native to northern China. The final intermediate, optically active biaryl compound 129 was treated with Sml2 in the presence of rBuOH and HMPA to provide isoschizandrin (130) in 85% yield as a >18 1 mixture of diastereo-mers (Scheme 25.62). 

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