Diastreoselective addition of Alkylidene succinimides to non-racemic sulfinimines; Towards the total synthesis of nakadomarin A

Abstract

The thesis titled “Diastereoselective addition of alkylidene succinimides to non-racemic sulfinimines: Towards the total synthesis of (+)-nakadomarin A” describes a systematic study on the addition of sodium enolates of alkylidene succinimides to non-racemic sulfinimines. Addition of the succinimide derived from aromatic aldehydes to sulfinimines derived from aliphatic aldehydes provided the addition products as a mixture of separable diastereomers in good yields. Alkylidene succinimides prepared from aliphatic aldehydes could add to the sulfinimines derived from aromatic aldehydes. Addition of the succinimide derived from ethyl glyoxylate to sulfinimines derived from aliphatic aldehydes furnished the addition products with isomerization of the double bond. The addition was found to be highly diastereoselective affording the functionalized maleimides in >99:1 diastereoselectivity. The addition of lithium enolates of alkylidene succinates to non-racemic sulfinimines afforded the addition products in excellent diastereoselectivities. Transformation of the addition products to functionalized pyrrolidinones and pyrrolidines is highlighted. Efforts towards the total synthesis of (+)-nakadomarin A are delineated in the other section. Michael addition of an imidate derived from Ellman sulfinimine to α, β- unsaturated diester is the pivotal reaction en route to the target compound. Acid mediated intramolecular cyclization of functionalized furan onto N-acyliminium ion to furnish the core structure of (+)-nakadomarin A is another key reaction in the synthesis.