Piperidines via Ammonium Ylide [1,2]-Shifts: A Concise, Enantioselective Route to (-)-Epilupinine from Proline Ester

Abstract

We have recently developed a new route to substituted piperidines from simple acyclic diazo ketone precursors by way of the Stevens [ 1,2]-shift of cyclic ammonium ylides.1 Previous reports of moderate to high levels of stereochemical retention by chiral migrating groups2 suggested the examination of diazo ketones bearing pendant, optically active a-amino acid derivatives. Further, the use of a cyclic amino acid such as proline would permit the rapid construction of more elaborate, bicyclic skeletons. Potential application tovarious lupin alkaloid3g4 (Chart (5) Reviews: (a) Ye, T.; McKervey, A. Although an excess of 4s was required, it could be recovered at the end of the reaction in ca. 50% yield. On larger scale reactions (220 mmol of S), 3 q u i v of 4s could be used with little or no diminution in yield.(8) Diazo ketone 9 derived from optically pure 4b was analyzed via IH NMR using Eu(hfc)l, and the spectra were compared with those of racemic 9. See supplementary material for details.(9) Ratios of 8a/8b were determined via integration of the benzyl ester methylene resonances in the 'H NMR spectra.

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…As shown in Scheme 261, copper-catalyzed cyclization of the proline-derived starting material generates two diastereomeric spirocyclic ylides which undergo subsequent [1,2]rearrangement to provide the quinolizidine products (84% yield), the major isomer of which is then converted to 208 in three steps. 601,602 This methodology has been applied to the synthesis of several biologically active compounds, including the cephalotaxine ring skeleton (Scheme 262), 603 isoindolobenzazepine alkaloids (Scheme 263), 604 and the novel pyrrolo[1,2-a][1,4]-benzodiazepinone system (Scheme 264). 605 3.6.3.3.…”

Silylene oxonium ylides: di-tert-butylsilylene insertion into C–O bonds

“…The loss of enantioselectivity can be explained by the production of allylic silane 52′ being formed concurrently with allylic silane 52 . Retention of facial selectivity appears to be consistent with a [1,2]-Stevens rearrangement pathway20-22 with some allylic transposition23 occurring.…”

Construction of N‐Heterocycles through Cyclization of Tertiary Amines

“…Apparently, except for the [2,3] rearrangement, the ammonium ylide could undergo a Stevens‐type rearrangement to provide different N‐heterocyclic structures. West and co‐workers developed several such cyclization reactions to access different N‐heterocycles in the presence of copper or rhodium catalysts (Scheme ) . Typically, in the presence of a transition‐metal catalyst, tertiary amines 130 , 131 bearing a diazo moiety could in situ generate ammonium ylides M67 – M68 , which subsequently would undergo [1,2]‐migration of one of the substitutions on the nitrogen to provide N‐heterocycles 132 , 133 .…”

“…West and co-workers developed severals uch cyclization reactions to access different N-heterocycles in the presence of coppero rr hodium catalysts (Scheme 55). [107][108] Typically,i nt he presence of at ransitionmetal catalyst, tertiarya mines 130, 131 bearingadiazo moiety could in situ generate ammonium ylides M67-M68,which subsequently would undergo [1,2]-migration of one of the substitutionsont he nitrogen to provide N-heterocycles 132, 133.…”