The enantiospecific synthesis of (+)-monomorine I using a 5-endo-trig cyclisation strategy

• Published in: Beilstein journal of organic chemistry Vol. 3; no. 1; p. 39
• Main Authors: Berry, Malcolm B, Craig, Donald, Jones, Philip S, Rowlands, Gareth J
• Format: Journal Article
• Language: English
• Published: Germany BioMed Central Ltd 08-11-2007; Beilstein-Institut
• Subjects: Chemistry; Full Research Paper
• ISSN: 1860-5397; 1860-5397
• DOI: 10.1186/1860-5397-3-39

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.