The utilization of stoichiometric molybdenum pi-complexes for the synthesis of substituted piperidines.

摘要

The goal of extending the utilization of stoichiometric molybdenum complexes in the synthesis of substituted heterocycles to include the synthesis of various polysubstituted piperidines has been addressed. A variety of 6-membered nitrogen heterocycles, including (2R*, 6S*)-6-acet oxy-2-alk yl-1-(tol u ene-4-sulf on yl)-1,6-di hy dro-2H-py ri din-3-one, (2R*,6S*)-2-alk yl-6-acet oxy-1,6-di hy dro-2H-py ri din-3-one-1-carb ox yl ic acid tert-butyl ester, and benzyl 1,6-dihydro-3(2H)-pyridinone-1-carboxylate have been synthesized from inexpensive starting materials, and their corresponding molybdenum eta3-allyl complexes have been synthesized.; The utility of each class of molybdenum eta3-allyl complex as a synthetic intermediate was investigated. It was found that di car bon yl [hy dri do tris(1-pyraz ol yl)bo ra to][(3R*,4R*,5S*)-benz yl eta-(3,4,5)-3-meth oxy-1,2,5,6- te tra hy dro py ri din-3-yl-1-carb ox yl ate] molyb den um was the most synthetically useful of these complexes. A complete multistep synthetic methodology was developed, utilizing this complex as the starting point. A variety of substituents was added to the 2- and 6-positions of this complex, rapidly forming a large library of analogous molybdenum complexes. These substituents included some highly functionalized examples such as esters, ketones, alkynes, etc. The molybdenum/auxiliary ligand moiety completely controlled the regio- and stereochemistry of this multistep sequence. The subsequent decomplexation allowed for the placement of additional functionality at C3--C5 of the resulting uncomplexed piperidines. Again, the molybdenum/auxiliary ligand moiety controlled the regio- and stereochemistry of this additional functionality.; The application of this methodology to the synthesis of en an tio mer ic al ly pure organic products was also achieved. Through the use of the commercially available chiral auxiliary R-(--)-pan to lac tone, the en an ti o mer ic al ly pure molyb den um com plex es di car bon yl [hy dri do tris (1-py ra zol yl)bo ra to] [(3S,4S,5R)-(R-pan to lac ton yl) eta-(3,4,5)-3-meth oxy-1,2,5,6-te tra hy dro py ri din-3-yl-1-carb ox yl ate] molyb den um and di car bon yl [hy dri do tris (1-py ra zol yl) bo ra to][(3R, 4R, 5S)-(R-pan to lac ton yl) eta-(3, 4, 5)-3-meth oxy-1,2,5,6-te tra hy dro py ri din-3-yl-1-car boxy late] molybden um were isolated through crystallization. An X-Ray crystal structure of di car bon yl [hy dri do tris(1-py- ra zol yl)bo ra to][(3S,4S,5R)-(R-pan to lac ton yl) eta-(3,4,5)-3-meth oxy-1,2,5,6- te tra hy dro py ri din-3-yl-1-car box yl ate] molybdenum confirmed the absolute stereo chemistry of these complexes.