Ons are essential and auxiliary-derived by-products can complicate isolation on theOns are required and auxiliary-derived

Ons are essential and auxiliary-derived by-products can complicate isolation on the
Ons are required and auxiliary-derived by-products can complicate isolation from the solutions.[26e, 26f] Evans and Weber developed -isothiocyanato acyl oxazolidinones as substrates in their diastereoselective tin-mediated aldol chemistry,[28] and notable advances happen to be recorded by the Willis,[29] Feng,[30] and Seidel[31] groups to transform this strategy into processes mediated by MMP-10 Source chiral catalysts. These -isothiocyanate methodologies afford thiocarbamate heterocycles as goods, which conveniently serve to guard the amine and alcohol functionalities of the aldol NPY Y4 receptor MedChemExpress adducts, but require a 3-step procedure to reveal the embedded -amino acids. Methods 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 different notable strategy employs Schiff bases of glycine tert-butyl esters in aldol reactions with aldehyde substrates to provide aldol addition merchandise which might be then treated with acid to reveal the embedded -hydroxy–amino esters. Advances in this area were reported by the Mukaiyama,[37] Belokon,[38] Miller,[39] and Corey[40] groups, and subsequently quite a few modifications have emerged that supply each syn[41] and anti[42] items. Whilst these solutions are easy as a result of the facile enolization of glycine Schiff bases plus the direct conversion of the aldol goods into -hydroxy–amino esters, they frequently endure from poorAngew Chem Int Ed Engl. Author manuscript; available in PMC 2015 April 25.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSeiple et al.Pagediastereoselectivities, narrow substrate scope, and often demand further functionalization to permit separation of syn and anti aldol addition goods.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, offering oxazoline-4-carboxylate products that can be converted to -hydroxy–amino acids upon treatment with robust 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] plus the Evans group.[45] These systems had been located to be hugely successful only with aromatic aldehyde substrates, and conversion of the oxazoline items to -hydroxy–amino acids requires three actions and harshly acidic circumstances. Barbas, Tanaka, and coworkers reported a strategy for the aldolization of phthalimidoacetaldehyde catalyzed by proline that accomplished high 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, although very stereoselective for certain aldehyde substrates, is restricted in scope.[47] We think aldolization of pseudoephenamine glycinamide gives numerous advantages. Enolization of 1 proceeds below incredibly mild circumstances (LiHMDS, LiCl) with out metal additives, and the syn aldol products are readily obtained in stereoisomerically pure form by column chromatography. A broad selection of electrophiles, like alkyl and aryl aldehydes and ketones, undergo efficient aldolization with 1, whereas numerous other glycine equivalents react effectively only with aryl.