Al catalysts. These -isothiocyanate methodologies afford thiocarbamate heterocycles as solutions, which conveniently serve to shield the amine and alcohol functionalities on the aldol adducts, but call for a 3-step process to reveal the embedded -amino acids. Approaches employing chiral glycine enolate equivalents have also been reported by the Bold,[32] Iwanowicz,[33] Caddick,[34] and Franck[35] groups. Hydroxymethylations of alanine equivalents to type -alkyl serine derivatives have also been reported.[36] A further notable strategy employs Schiff bases of glycine tert-butyl esters in aldol reactions with aldehyde substrates to provide aldol addition solutions that are then treated with acid to reveal the embedded -hydroxy–amino esters. Advances in this area had been reported by the Mukaiyama,[37] Belokon,[38] Miller,[39] and Corey[40] groups, and subsequently various modifications have emerged that present both syn[41] and anti[42] products. Although these procedures are hassle-free due to the facile enolization of glycine Schiff bases and also the direct conversion of your aldol products into -hydroxy–amino esters, they usually endure from poorAngew Chem Int Ed Engl. Author manuscript; obtainable in PMC 2015 April 25.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author PKCĪ³ MedChemExpress ManuscriptSeiple et al.Pagediastereoselectivities, narrow substrate scope, and regularly call for additional functionalization to permit separation of syn and anti aldol addition solutions.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIto, Hayashi, and coworkers employed -isocyano esters and amides in aldol reactions catalyzed by chiral gold(I) complexes, giving oxazoline-4-carboxylate merchandise that may be converted to -hydroxy–amino acids upon remedy with powerful acid.[43] Oxazoline-4carboxylates have also been constructed by the addition of 5-alkoxyoxazoles to aldehydes catalyzed by chiral aluminum catalysts, as demonstrated by Suga and Ibata[44] along with the Evans group.[45] These systems had been located to become hugely productive only with aromatic aldehyde substrates, and conversion from the oxazoline solutions to -hydroxy–amino acids demands three steps and harshly acidic situations. Barbas, Tanaka, and coworkers reported a technique for the aldolization of phthalimidoacetaldehyde catalyzed by proline that achieved higher enantio- and diastereoselectivities, but only with -branched aldehyde substrates.[46] The Wong group has developed methodology for chemoenzymatic aldolization of glycine catalyzed by threonine aldolases that, whilst hugely stereoselective for specific aldehyde substrates, is restricted in scope.[47] We believe aldolization of pseudoephenamine glycinamide presents several benefits. Enolization of 1 proceeds beneath quite mild situations (LiHMDS, LiCl) with no metal additives, along with the syn aldol goods are readily obtained in stereoisomerically pure kind by column chromatography. A broad collection of electrophiles, like alkyl and aryl aldehydes and ketones, undergo efficient aldolization with 1, whereas many other glycine equivalents react Phospholipase site effectively only with aryl or alkyl aldehydes, and pretty couple of are reported to react effectively with ketones.[48] Using the exception of chemoenzymatic approaches,[47] the aforementioned glycine equivalents all demand shielding with the -amino group, but this is not required with our approach. Hydrolysis on the aldol adducts of 1 proceeds beneath unusually mild situations in comparison to other glycine equivalents, and bot.