Diastereoselective synthesis of beta-substituted-alpha,gamma-diaminobutyric acids and pyrrolidines containing multichiral centers.

A convenient and efficient way for the highly diastereoselective synthesis of beta-substituted-alpha,gamma-diaminobutyric acids and pyrrolidines containing multichiral centers has been well-developed. Michael addition of chiral tricyclic iminolactones 1 and 2 to nitroalkenes afforded the adducts in good yields (up to 95%) and excellent diastereoselectivities (up to dr > 99:1) when titanium(IV) isopropoxide was used. Configuration of the second new stereocenter was decided by the substitution of nitroalkene. Selective reduction and hydrolysis of the Michael adducts furnished the desired beta-substituted-alpha,gamma-diaminobutyric acids in good yields and high enantiomeric excesses (>99% ee). Synthesis of pyrrolidines containing multichiral centers has also been accomplished in good to excellent yields and diastereoselectivities under mild conditions via Michael-Mannich tandem reactions using Cu(OTf)(2) or AgOTf as an activating reagent for aliphatic nitroalkenes.