161453-17-4Relevant articles and documents
Trading N and O. Part 4: Asymmetric synthesis of syn-β-substituted-α-amino acids
Davies, Stephen G.,Fletcher, Ai M.,Greenaway, Catherine J.,Kennedy, Matthew S.,Mayer, Christoph,Roberts, Paul M.,Thomson, James E.
, p. 5049 - 5061 (2018)
A total of nine enantiopure syn-β-substituted-α-amino acids have been synthesised, comprising both syn-β-hydroxy-α-amino acids and syn-β-fluoro-α-amino acids. The key step in the synthetic strategy towards these syn-β-substituted-α-amino acids involves a stereospecific rearrangement, which proceeds via the intermediacy of the corresponding aziridinium ions. The requisite enantiopure syn-α-hydroxy-β-amino esters were prepared via asymmetric aminohydroxylation of the corresponding α,β-unsaturated esters followed by epimerisation of the resultant anti-α-hydroxy-β-amino esters at the C(2)-position. Subsequent activation of the α-hydroxy moiety as a leaving group followed by displacement by the β-amino substituent gave the corresponding aziridinium species. Regioselective in situ ring-opening of the aziridinium intermediates with either water or fluoride gave the corresponding syn-β-hydroxy-α-amino ester or syn-β-fluoro-α-amino ester, respectively, and N-deprotection and ester hydrolysis afforded the target syn-β-substituted-α-amino acids as single diastereoisomers in good overall yield.
Asymmetric Synthesis of β-Amino-α-Hydroxy Acids via Diastereoselective Hydroxylation of Homochiral β-Amino Enolates
Bunnage, Mark E.,Chernega, Alexander N.,Davies, Stephen G.,Goodwin, Christopher J.
, p. 2373 - 2384 (2007/10/02)
The highly diastereoselective conjugate addition of lithium N-benzyl-N-α-methylbenzylamide with enoate acceptors, and the electrophilic hydroxylation of the resultant β-amino enolates with (camphorsulfonyl)oxaziridine, is identified as a direct and general strategy for the asymmetric synthesis of homochiral β-amino-α-hydroxy acids and their derivatives.A structurally diverse array of β-amino enolate substrates can be hydroxylated with generally excellent anti diastereoselectivity (>90percent d.e.) using this protocol; an alternative stepwise hydroxylation procedure, where the β-amino enolate is prepared by enolisation of the preformed conjugate adduct is also found to lead to formation of the anti diastereomer.The diastereofacial selectivity of enolate hydroxylation appears to be under predominantly substrate-controlled asymmetric induction, although a measurable degree of chirality predominantly substrate-controlled asymmetric induction, although a measurable degree of chirality recognition with the oxaziridine reagent can be observed.Homochiral β-amino-α-keto esters are also prepared and their stereoselective reductions examined.
