Ammonium ylides epilupinine

The key step in the total synthesis of (—)-epilupinine 253 involved the ring expansion of a proline-derived spirocyclic ammonium ylide to give 252 through a [1,2] Stevens rearrangement, as shown in Scheme 51 <1997T16565>. 

The cyclic ammonium ylide/[l,2]-shift approach has been successfully applied by West and Naidu to a key step in the total synthesis of (—)-epilupinine, one of the biologically active lupin alkaloids. Cu(acac)2-catalyzed diazo decomposition of enantiomeric pure diazoketone 160 in refluxing toluene generates a spiro ammonium ylide 161 and 162, which then undergoes [l,2]-shift to give rise to a quinolizidine skeleton as a mixture of diastereomers (95 5) (Scheme Major diastereomer 164 has enantiomeric purity of 75% ee. The partial retention of stereo-... 

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). 

Naidu BN, West FG. A short, enantioselective synthesis of (—)-epilupinine from proline via a spirocyclic ammonium ylide. Tetrahedron 1997 53(48) 16565-16574. 

West FG, Naidu BN. Piperidines via ammonium ylide [1,2]-drifts a concise, enantioselective route to (—)-epilupinine flom proline Ester. 7. Am. Chem. Soc. 1994 116(18) 8420-8421. 

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