Cyclohydrocarbonylation-Based Strategy toward Poly- Substituted Piperidines

Abstract

Convenient accesses to enantiomerically pure 2-, 2,3-, 2,6-, 2,3,6-substituted piperidines and 1,4-substituted indolizine are described. At first, indium-mediated aminoallylation and -crotylation of aldehydes with (R)-phenylglycinol or (1R,2S)-1-amino-2-indanol gave homoallylamines with high stereocontrol. Then, these products, submitted to a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation, afforded perhydrooxazolo[3,2-a]piridines whose oxazolidines are opened with nucleophiles. Finally, the removal of the chiral auxiliaries delivered the enantiomerically pure piperidines.

Multicomponent Mannich‐Like Reactions of Organometallic Species

“…They noticed that the use of an H 2 O/THF mixture was crucial to favor the formation of the desired Mannich products 33 (Scheme ). A similar methodology using chiral amines was subsequently used by Taddei and co‐workers for the preparation of densely substituted piperidines …”

“…A similar methodology using chiral amines was subsequently used by Taddei and coworkers for the preparation of densely substituted piperidines. [47] The preparation of homoallylamines through Mannich reactions with allylboron species was first reported by Kobayashi and co-workers in 2004. [48] They initially disclosed uncatalyzed MCRs between aldehydes 3b, allylboronates 35, and liquid ammonia.…”

A highly stereo-controlled protocol to prepare pipecolic acids based on Heck and cyclohydrocarbonylation reactions

“…11 Domino hydro-formylation-cyclisation of olefins involving a nitrogen nucleophile (cyclohydrocarbonylation, CHC) 12 is a powerful method to prepare multifunctional heterocycles such as indolizidine, 13 tetrahydroquinolines, 14 quinolizidines 15 and piperidines. 16,17 We sought to expand the scope of our CHC process for the synthesis of piperidine 17 with the aim of preparing enantiomerically pure di-and tri-substituted pipecolic acids (Scheme 1).…”

LaCl3·7H2O as an Efficient Catalyst for One-Pot Synthesis of Highly Functionalized Piperidines via Multi-component Organic Reactions

“…A variety of structural features surrounded the naturally occurring and synthetically prepared piperidines, among them many exhibit significant biological properties including anti-HIV, anticancer, antimycobacterial, antimicrobial, antimalarial, antiinflammatory, antiinsecticidal and they are potent inhibitors for many biological systems [10][11][12][13][14]. Much considerable efforts have been focused on the synthetic methods and some of the synthetic routes have been recommended for the synthesis of highly substituted piperidines essentially intramolecular Mannich reaction [15], cyclohydrocarboxylation [16], aziridine ring expansion [17], radical cyclization [18], domino reaction [19], Diels-Alder reaction [20], imino Diels-Alder reaction [21] and domino imino-aldol-azaMichael addition [22]. Recently one-pot synthesis of these scaffolds has been achieved by employing InCl 3 [23], bromodimethylsulfonium bromide [24], L-proline/TFA [25], tetrabutylammonium tribromide [26], molecular I 2 [27], CAN [28], ZrOCl 2 Á8H 2 O [29], picric acid [30], thiourea dioxide (TUD) [31], BF 3 -SiO 2 [32], VCl 3 [33] and Bi(NO 3 ) 3 Á5H 2 O [34] as efficient catalysts.…”