Hinokinin synthesis

Honda T, Kimura N et al (1994) Chiral synthesis of lignan lactones, (—)-hinokinin, (—)-deoxypodorhizone, (—)-isohibalactone and (—)-savinin by means of enantioselective deprotonation strategy. J Chem Soc Perkin Trans 1 1043-1046... 

The formation of the endocyclic double bonds of unsaturated lactones has been accomplished via the rDA reaction. The preparation of 2-alkyl-2-butenolactones, such as (179), by a method that incorporates the rDA reaction as a key step has been a q>lied to the synthesis of butyrolactone lignans such as ( >-hinokinin (180) as shown in equation (80). An extensive study of the preparation of substituted 2-bute-nolides (183) has been reported. The mono-, di- and tri-alkyl bicyclobutenolides are prepared by reacting adducts (181) with Grignard reagents or with LDA followed by alkyl halides. Alkylated adducts (182) were then either directly distilled under vacuum or heated in a sealed tube to give the alkylated 2-bute-nolides (183) (equation 81). " ... 

Further general route to 2-alkyl-2-butenolactones via the retro Diels-Alder reaction was developed. Fig, 5, [23]. Hydrolysis of a known lactone (15), subsequent esterification with diazomethane, and treatment with dihydropyran afforded a stereoisomeric mixture of pyranyl ether. Alkylation of the pyranyl ether with various alkyl halide yielded alkylated products (16). The retro Diels-Alder reaction of 16 was performed by heating at 200-280 C in a sealed tube to give 2-alkyl-2-butenolactones (17). The utility of the butenolactones was demonstrated by the synthesis of hinokinin (18) and dehydrolappaol A dimethyl ether (19). Similarly rather mild, simple synthesis of a-methylene-y-alkylbutyrolactones was deviced using dimethylfulvene as a protective group for the double bond, Fig. 6. [24], The... 

A third approach to asymmetric synthesis involving oxidative dimerisation of dihydrocinnamic acid derivatives is shown in scheme 13 ( f. scheme 7) [64,65]. By choosing an appropriate chiral auxiliary, either (-)- or (+)-hinokinin, for example, can be prepared. In either case removal of the chiral auxiliary leads to an anhydride having C2 symmetry which can be reduced to the lactone. 

Using Doyle s second-generation imidazolidinone catalyst system, Rh2(MPPlM)4, a series of benzyl substituted y-butyrolactones was synthesized by intramolecular C-H activation. The strategy was applied to the synthesis of various ligands such as enterolactone (202), hinokinin, and isodeoxypodophyllotoxin. " ... 

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