Piperidines stereoselective synthesis

A review was published covering recent progress in the stereoselective synthesis of piperidines <00S1781>. Routes described in detail include those derived from the chiral-pool, chiral auxiliaries, and catalytic asymmetric methodology. 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

The resulting derivatives (269) can be considered as strategically important intermediates in the synthesis of glycosidase inhibitors and carbocyclic nucleosides (150). A new approach to the stereoselective synthesis of the piperidine ring with the use of [4+ 2] [3+ 2]-cycloaddition from specially prepared substrates is also very interesting (431)b, c. In the context of this problem, the conditions for the formation of systems containing quaternary vicinal stereocenters were found. 

DFT Based Analysis for The Regio- and Stereoselective Synthesis of Tetrasubstituted Isoxazolidines From Cinnamoyl Piperidine Derivatives... 

Stereoselective synthesis of trans 4-chloro-2-substituted piperidines can be achieved by the reaction of epoxides and N-protected homoallyllic amines using BiCl3 as the Lewis acid catalyst (Fig. 3). This method furnishes very good generality with respect to various epoxides with a regioselectivity that favors the trans-... 

Further acid-catalyzed reactions include the use of />-toluene sulfonic acid-DMF in a cyclization of the protected amino acid 17 (DMF = dimethylformamide Scheme 15) <20040L4941>. This was the key step in the stereoselective synthesis of 5-hydroxypipecolic acid. A similar acid-catalyzed ring closure of a hemiacetal yielded the fused piperidine 18 <2004JOC1872> (Equation 32). The indolizidine alkaloid can be accessed by a Barton-Ester method utilizing a polyphosphoric acid (PPA) cyclization (Scheme 16) <1994T19157>. 

The synthesis of 2,4,6-trisubstituted piperidines has been reported via the generation of a fused cyclic intermediate in a three-component reaction using typical palladium-based chemistry (Scheme 112) <20060L3813, 20060L3809>. Stereocontrol was observed and the same intermediate was used in the stereoselective synthesis of the indolizidine alkaloid (—)-dendroprimine. 

Pandey, G., Devi Reddy, G., and Chakrabarti, D. (1996) Stereoselectivity in the photoinduced electron transfer (PET) promoted intramolecular cyclisations of l-alkenyl-2-silyl-piperidines and -pyrrolidines rapid construction of 1-azabicyclo [m.n.o] alkanes and stereoselective synthesis of ( )-isoretronecanol and ( )-epilupinine. Journal of the Chemical Society, Perkin Transactions 1, 219-224. 

Laschat, S. Dicker, T. Stereoselective Synthesis of Piperidines, Synthesis 2000, 1781-1813. 

A stereoselective synthesis of 2,3,5,6-tetra- and 2,3,4,5,6-penta-substituted piperidines was achieved from oxidative cleavage of 2-azabicyclo[2.2.2]octane Diels-Alder adducts 176 derived from dihydropyridine 177. Appropriate functional group interconversions of the amidine and ester functionalities in 176 ultimately gave densely functionalized piperidines such as 178 <05OL5773> (Scheme 51). 

Stereoselective synthesis of piperidines , Laschat, S. and Dickner, T, Synthesis, 2000, 1781. 

A short, convenient, stereoselective synthesis of pepper-derived alkaloids has been carried out by condensing piperonal with the ylide from methyl (E)-4-(diethylphosphono)-2-butenoate to give methyl (E,E)-5-(1,3-benzodioxol-5-yl)-2,4-pentadienoate, which on methoxide-catalysed aminolysis (piperidine, pyrrolidine, etc.) gave the required alkaloid. 

This reaction offers a stereoselective synthesis of a-linked glucosyl asparagine derivatives from both anomers of pent-4-enyl D-glycopyranoside. The pent-4-enyl 2,3,4,6-tetra-0-benyl-a-/p-D-glucopyranoside starting material for this reaction can be prepared easily in two steps from a-/p-glycopyranose [84]. For selective A-deacetylation of the product best results are obtained with piperidine which affords the a-linked asparagine derivate in 89% yield, the yield of the acetamido side product was reduced to 3.5%. The reaction time is also shortened to 5.75 h (when diethylamine was employed, the reaction was complete after 39 h with worse yields). Note that no reaction occurs when diisopropylamine is employed. 

Zech, G., Kunz, H. (2004). Synthesis of a polymeric-bound galactosylamine and its apph-cation as an immobilized chiral auxiliary in stereoselective synthesis of piperidine and amino acid derivatives. Chemistry - A European Journal, 10, 4136-4149. 

There is continued interest in chiral syntheses of pyrrolidines, piperidines, and related bicyclic systems. A review has appeared, in Russian, on the stereoselective synthesis of proline and pipecolic acid derivatives from sugars. The antifungal pyrrolidine (+)-preussin (74) has been made from the glucose-derived epoxide (73) as indicated in Scheme 16,58 whilst... 

Z)-Alk-2-enenitriles are also available from the hydrocyanation of acetylenes, which occurs with cis stereospecificity when catalysed by a nickel(O) complex, and from the stereoselective cyanation of vinyl halides, catalysed by tetracyano-cobaltate(i). The latter procedure is equally applicable to the stereoselective synthesis of the corresponding ( )-isomers. Also, the ( )- and (Z)-isomers (17) and (18) react with piperidine with retention of configuration to provide (19) and (20) respectively (Scheme 30). In contrast, the corresponding reaction with sodium methoxide gives rise to the (Z)-isomer only. 

Laschat S, Dickner T. Stereoselective synthesis of piperidines. Synthesis 2000 (75) 1781-1813. 

Wasserman, H.H., Rodriques, K., and Kucharczyk, R. (1989) The imine-epoxide rearrangement in the formation of trans-2,6-disubstituted piperidines. A stereoselective synthesis of ( )-teneraic... 

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