Homoallylic derivatives 1,5-diene synthesis

Pancratistatln. The first total synthesis of ( )-pancratistatin (94) (Scheme 14), the structurally most complex of narciclasine alkaloids, was achieved by Danishefsky [27]. The requisite starting material, the substituted benzaldehyde 95 prepared from pyrogallol in six steps in 18% overall yield, was converted via the homoallylic alcohol 96 into the diene 97. Reaction of 97 with 2-nitrovinylsulphone yielded the cycloadduct 98, which on treatment with tributyltinhydride and 2,2 -azobisisobutyronitrile furnished the cyclohexadiene 99. Whilst the cyclisation of the silylether 99 or the derived phenol, under the influence of iodine, could not be accomplished, the more nucleophilic stannylether did participate in the desired ring closure and provided via the iminium salt, the iodolactone 100 on aqueous work-up. 

The first total synthesis of ( )-lycoridine margetine (33), a member of the non-basic alkaloids which possess antimitotic activity has been achieved (Scheme 3). The homoallylic alcohol (26) served as a latent diene in a Diels-Alder reaction with ethyl acrylate to give a diastereomeric mixture of adducts which upon base equilibration and hydrolysis provided the tmns-acid (27). Modified Curtius reaction on (27) afforded the corresponding isocyanate which was cyclized to the lactam (28) in 89% yield by a new method using boron trifluoride etherate. Compound (28) was converted into an N-acetyl derivative which upon basic hydrolysis gave the acid (29). Treatment of (29) with NBS followed by reflux in pyridine solution gave the lactone... 

Silver-initiated ring cleavage of bicyclo[1.1.0]butanes in protic solvents leads predominantly to mixtures of cyclopropanes and the corresponding dienes, e.g. a mixture of the norcarane ether 32 and the corresponding homoallylic ether 33 is observed in the reaction of 2,6-dimethyl-tricyclo[4.1.0.0 ]heptane (31) with silver perchlorate. This reaction is of little practical value for the synthesis of cyclopropane derivatives from bicyclo[1.1.0]butanes. 

Intramolecular ene reactions take place readily, even with compounds containing a normally unreactive enophile. The cyclization is parhcularly effective for the formation of hve-membered rings, although six-memhered rings can also be formed from appropriate unsaturated compounds. The geometrical constraints imposed on the transition state often result in highly selective reactions. For example, the homoallylic alcohol 242 with an axial alcohol substituent was the exclusive product from the cyclization of the unsaturated aldehyde 241 (3.157). In a synthesis of the neuroexcitatory amino acid (—)-a-kainic acid 245, the diene 243, itself prepared from (5)-glutamic acid, was cyclized to the pyrrolidine derivative 244 with almost complete stereoselectivity (3.158). ... 

In the course of their synthesis of a ring-expanded bryostatin analog 131, Trost et al. studied the RCM cyclization of substrate 128, which was armed for a potential RRCM reaction (Scheme 9.31) [36]. This complex polyene cycUzed very cleanly under the action of [Ruj-III to produce the cyclic diene 129. There was no evidence of formation of the smaller RRCM product The rate of the relay event here is presumably lowered by the pair of quatemized carbons aUylic ( ) and homoallylic (A) to C17 in the alkylidene derived from 128. 

---