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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
The enantiospecific synthesis of (+)-monomorine I using a 5-endo-trig cyclisation strategy
Malcolm B Berry1, Donald Craig, Philip S Jones
1Department of Chemistry, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. malcolm.b.berry@gsk.com
Abstract:
We have developed a general strategy for the synthesis of 2,5-syn disubstituted pyrrolidines that is based on the multi-faceted reactivity of the sulfone moiety and a 5-endo-trig cyclisation. This methodology was applied to the synthesis of indolizidine alkaloid monomorine I. Two factors were key to the success of this endeavour; the first was the choice of nitrogen protecting group whilst the second was the conditions for the final stereoselective amination step. Employing a combination of different protecting groups and an intramolecular reductive amination reaction we were able to prepare (+)-monomorine I in just 11 steps from commercially available D-norleucine in a completely stereoselective manner.
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