Epilupinine diastereoselectivity

West and Naidu found that the diazoketone 358, prepared by alkylating the benzyl ester of L-proline with 5-bromo-l-diazopentan-2-one, cyclized to give a transient spirobicyclic ammonium ylide 359 when heated with coppeifll) acetylacetonate in toluene (Scheme 44) (355,356). This unstable ylide underwent a diastereoselective [1,2]-Stevens rearrangement to give the quinolizidinone 360 and its bridgehead epimer in a ratio of 95 5. However, some racemization (possibly through an achiral diradical intermediate) must have occurred, since 360 had an ee of only 75%. Reduction of the ester and defimctionalization of thioketal 361 with the unusual combination of sodium and hydrazine in hot ethylene glycol completed a synthesis of the unnatural (- )-enantiomer of epilupinine (ent-331). 

Reductive Carbocyclization of Dienes. Carbocyclization-silylation of 1,5- and 1,6-dienes such as 39 (52-58) as well as enynes (59) catalyzed by Cp 2YMe THF or Cp 2LuMe THF is a highly regio- and diastereoselective process, which tolerates various functional groups such as ethers, thioacetals, and tertiary amines in spite of the strong Lewis acidity of the catalysts (Scheme 22). This reaction has been applied to the synthesis of izidine alkaloids such as epilupinine 43 (Scheme 23) (54). 

This method was proved to be applicable for the total synthesis of ( )-epilupinine, in which high diastereoselectivity was achieved through an organoyttrium-catalyzed sequential cyclization/silylation reaction (Scheme 12.82) [180]. The catalytic cyclooligomerization proceeded rapidly and was unaffected by the presence of a... 

There are surprisingly few common approaches to the lupin indolizidines and their quinolizidine homologs despite their structural similarity. One such approach was recently reported by Cutter et al., who used imino—aldol reactions of phenyl 5-chlorovalerate (992) as the starting point for the synthesis of both (—)-tashiromine (ent-929) and (—)-epilupinine (ent-921) (Scheme 123). " The addition of the hthium enolate of 992 to the (S)-N-sulfinylimine (- -)-993 proved to be highly diastereoselective, giving a 78% yield of the adduct (- -)-994 and its (S,S)-isomer (+)-995 in a ratio of 16 1. The stereochemistry of 994 was confirmed by X-ray diffraction. 

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