Enantioselective synthesis of optically pure (R)- and (S)-β-lysine via nitrone cycloaddition

Abstract

Optically pure (R)and (S)-P-lysines have been obtained via cycloaddition of chiral nitrone (4) to vinyl acetate, followed by facile chromatographic separation of the four resulting acetates (5) into two pairs of C-5 epimers and conversion of each pair into diastereoisomerically pure isoxazolidinone (7a or b).

Allylic 1,3-strain as a controlling factor in stereoselective transformations

“…137 For this type of reaction the difference in inert volumes of Ph and CH3 may not be marked enough.…”

Asymmetric 1,3-Dipolar Cycloaddition Reactions

“…The most commonly used chiral substituent at the nitrogen atom is the 1-phenylethyl group. − The derived nitrones 7 are available from 1-phenethylamine 5 (Scheme ) and the substituent has the advantage that it can be removed from the resulting isoxazolidine product 8 , by hydrogenolysis. In the reduction step the isoxazolidine ring 8 is also opened to give the primary 3-amino alcohol 9 as outlined in Scheme .…”

“…Kametani et al applied 1,3-DC reactions of N- α-methylbenzyl nitrones with benzyl crotonates in the synthesis of (+)- and (−)-thienamycin and penem and carbapenem precursors. , In a similar manner, Overton et al have applied this type of nitrones in the 1,3-DC reaction with vinyl acetates for the synthesis of naturally occurring β-amino acids …”

The Total Synthesis of Aspidofractinine and Related Alkaloids

“…Debenzylation of 114 using Pd/C resulted in pentacyclic product 115 in 20 % yield over five steps. Further, compound 115 was oxidized to indolenine 74 by Swern oxidation [27] and direct intramolecular Mannich‐type cyclization [22] furnished (±)‐19‐ oxoaspidofractinine 75 . Ban and co‐workers have previously accomplished the total synthesis of aspidofractinine from 75 (Scheme 1b).…”