Asymmetric synthesis of 4-amino-γ-butyrolactones via lithium amide conjugate addition

Add time:09/05/2019    Source:sciencedirect.com

Upon treatment with homochiral lithium (R)-N-benzyl-N-(α-methylbenzyl)amide, γ-benzyloxy but-2-enoates undergo competitive conjugate addition and γ-deprotonation, while γ-tert-butyldimethylsilyloxy but-2-enoates undergo exclusive conjugate addition. Treatment of γ-benzyloxy or γ-tert-butyldimethylsilyloxy but-2-enamides with lithium (R)-N-benzyl-N-(α-methylbenzyl)amide furnishes exclusively the γ-benzyloxy- or γ-tert-butyldimethylsilyloxy-β-amino amide products of conjugate addition in high de. The γ-tert-butyldimethylsilyloxy-β-amino butanoate products of conjugate addition readily undergo O-desilylation and concomitant cyclisation to furnish 4-[N-benzyl-N-(α-methylbenzyl)amino]-γ-butyrolactone, which may be stereoselectively functionalised via deprotonation and alkylation to give the corresponding trans-3-alkyl-4-amino-γ-butyrolactones. Alternatively, stereoselective alkylation of γ-benzyloxy- or γ-tert-butyldimethylsilyloxy-β-amino butanoates and butanamides through enolate formation and alkylation following a tandem (via the (Z)-lithium enolate) or stepwise (via the (E)-lithium enolate) protocol gives a range of separable syn- and anti-α-alkyl-β-amino esters and amides. O-Silyl deprotection of the syn- and anti-α-alkyl-β-amino butanoates with TBAF and concomitant cyclisation provide trans-3-alkyl-4-amino-γ-butyrolactones, consistent with epimerisation to the thermodynamically favoured trans-lactone occurring upon deprotection.

We also recommend Trading Suppliers and Manufacturers of 4-(tert-Butyldimethylsilyloxy)benzyl chloride (cas 138585-09-8). Pls Click Website Link as below: cas 138585-09-8 suppliers

Prev:Diels–Alder cycloaddition of electrophilic 2H-azirines with 3-(3-(tert-butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-ones. Treatment of the cycloadducts under acidic conditions
Next:A convenient synthesis of functionalized isoxazolines and related 5-hydroxyisoxazolidine-4-carboxylates)