Prolines organocatalytic reduction

Hydroxy-proline trans-12) is a much less common natural amino acid found in mammalian collagen, whereas the cis diastereoisomer may eventually be synthesised in multigram scale by the baker s yeast reduction of the corresponding 3-keto-ester, with excellent selectivities. Thus, 12 or its derivatives have rarely been used in organocatalytic transformations. 

In 2006, Enders and Vrettou [32] reported a concise total synthesis of (-l-)-poly-oxamic acid (82) through an organocatalytic Mannich reaction (Scheme 17.12). Asymmetric Mannich reaction of ketone 79 and Boc-protected imine 80 using L-proline 24 afforded the adduct 81 in 85% yield as a mixture of diastereomers with 92% ee (>98 2 dr). A stereoselective reduction of 81 using L-selectride, followed by ozonolysis and subsequent acid deprotection completed the total synthesis of (-l-)-polyoxamic acid (82). 

While most successful asymmetric organocatalytic imine reduction methodologies are limited to N-aryl imines. Sun et al. reported in 2008 that a new chiral sulfinamide catalyst 90 derived from L-proline is highly efficient for the reduction... 

Quinine 84 and quinidine 85 are well-known medicinally important alkaloids as well as mother structures for organocatalysts. Hatakeyama and co-workers reported on organocatalytic asymmetric synthesis of a key intermediate for these alkaloids. They performed the intramolecular direct aldol reaction of bis aldehyde 79 in the presence of L-proline 57. After reduction of the ketone, syn-diol 80 and anti-diol 81 were obtained with high enantiose-lectivity (Scheme 27.14). The mixture was converted into the common intermediate 83 for quinine 84 and quinidine 85 via ketone 82. Quinine 84 and quinidine 85 were... 

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