Piperidine 6-amino-1-alkene

The authors extended this protocol toward the diastereo-selective synthesis of pyrrolidine and piperidine ring systems starting from unactivated amino alkenes," and nonracemic sultam derivative 95 in good yield as well as high enantioselectivity ee 94%) using the chiral Py-Box hgand (Scheme 40.20)." ... 

Ojima and coworkers have developed a similar approach to the synthesis of piperidine and related ring systems, which they describe as cyclohydrocarbonylation. In this approach, carbamate-protected allylglydnes (for example, 32) are subjected to rho-dium(I)-catalyzed hydroformylation in an alcohol solvent (Scheme 5.13) [17]. 6-Alkoxy-pipecolates 33 are isolated in good yield and were shown to be amenable to further stereoselective transformations. This methodology has recently been expanded to include fully intramolecular variants that can form two rings in a single reaction. Thus, alkenes 34 are subjected to the cyclohydrocarbonylation conditions to provide azabicy-clo[4.4.0]aUcane amino acids 35 which can serve as conformationaUy restricted dipeptide surrogates and /9-turn mimetics [18]. 

The products from alkene hydroamination are inherently lightly functionalized. To address this possible deficiency. Professor Marks also reported (J. Am. Chem. Soc. 125 15878, 2003) the cyclization of amino dienes such as 5. The cyclizations proceed with high selectivity for, the cis-2,6-dialkyl piperidines, and with a little lower selectivity for the trans 2,5-dialkyl pyrrolidine. The product alkenes are -95% E, the balance being a little Z alkene and the terminal alkene. 

N-Nitrosopiperidine (carcinogen) with oxygen adds photolytically to alkenes to give A(-(2-nitro-alkyl)piperidines. Indirect methods of preparing amino alcohols from alkenes include the well-known trans opening of epoxides with nitrogen nucleophiles and a recent, complementary, cis opening of... 

Another example of this category is the first dynamic kinetic resolution of a racemic a-amino aldehyde [93]. It has been shown that the N-tosyl-protected aldehyde 149 reacts with a near equimolar amount of chiral phosphonate 27e to afford vinylogous amino acid esters (R, )-150 with excellent diastereoselectivity and chemical yield. Similarly, the N-tosyl-protected piperidine 151 was converted into the trisubstituted alkene 152 with good diastereoselectivity and in high chemical yield by reaction with chiral phosphonate 28. In several cases, it has been shown that the selectivity obtained under dynamic conditions exceeds that obtained by a traditional kinetic resolution. The HWE products obtained appear to be attractive precursors for non-proteinogenic amino acids [83] as well as various alkaloids. 

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