An Efficient Access to Enantiomerically Pure Substituted Derivatives of Pipecolic Acid

Enantiopure bicyclic piperidinones: stereoselectivity in lactam enolate alkylations

“…The synthesis of substituted piperidines, piperidinones and indolizidines 1-5 is of importance because of their widespread occurrence in nature, their wide-ranging biological activity, and more recently for their conformational controlling properties. [6][7][8][9][10][11][12][13][14] Although a number of routes to these compounds have been reported, involving, for example, the elaboration of amino acids [15][16][17][18][19] or other chiral starting materials, [20][21][22][23][24][25][26] and chiral auxiliary mediated, 27-30 catalytic 31, 32 or desymmetrisation processes, [33][34][35] the most general strategies for piperidine synthesis appear to be the CN(R,S) method developed by Husson and Royer, 36 the 2,3-dihydro-4-pyridone strategy extensively developed by Comins,37,38 the bicyclic lactam methodology developed by Meyers, 39-41 and the chiral deprotonation mediated approach of Beak. 42 Of interest to us are such general approaches, enabling the preparation of piperidines, substituted at any or all of the ring carbons, in a diastereoselective and enantioselective manner, which are applicable to combinatorial or parallel synthetic technologies.…”

The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines

“…Existing methods for the synthesis of pipecolic acid and its derivatives have been reviewed, 47 and it is surprising that there have only been limited approaches to pipecolic acid derivatives via Prins reaction-type approaches. [48][49][50] Catalytic hydrogen using Pearlman's catalyst (Scheme 5a) simultaneously removed the chiral auxiliary and reduced the alkene to give enantiopure 6-substituted pipecolic acid derivatives (14) in excellent yields. The alkene moiety, however, had been designed into the products to be more useful than for simple reduction.…”

Synthesis of O‐ and N‐Heterocycles by Silyl‐Prins Cyclization of Allylsilanes

“…A different approach to azabicycles is the use of bis(electrophilic) aldehydes in aza‐Prins cyclizations. Puchot devised an elegant route for the synthesis of pipecolic acids, in which the key step was the stereoselective reaction between a chiral allylsilyl β‐amino alcohol and glyoxal. The dual condensation of the bis(nucleophilic) amino alcohol with glyoxal gives an intermediate hemiacetal iminium ion, which is readily captured by the allylsilane to afford a bicyclic compound with an exocyclic double bond (Scheme ).…”