Enantio- and Diastereoselective Two-Pot Synthesis of Isoquinuclidines from Glutaraldehyde and N‑Aryl Imines with DFT Calculations

A pot-economic method for the enantio- and diastereoselective synthesis of a [2.2.2] azabicyclic isoquinuclidine system is developed. This protocol involves the proline-catalyzed direct Mannich reaction-cyclization/IBX-mediated site-selective oxidation/NaBH4-reduction sequence between glutaraldehyde...

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Published in:Journal of organic chemistry 2019-10, Vol.84 (19), p.12408-12419
Main Authors: Ramaraju, Panduga, Pawar, Amol Prakash, Iype, Eldhose, Mir, Nisar A, Choudhary, Sachin, Sharma, Devinder Kumar, Kant, Rajni, Kumar, Indresh
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cited_by cdi_FETCH-LOGICAL-a248t-7eedeaca750b83d0b91f984251186b4afacf5f6bfcd5046909c4263a054258d83
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container_end_page 12419
container_issue 19
container_start_page 12408
container_title Journal of organic chemistry
container_volume 84
creator Ramaraju, Panduga
Pawar, Amol Prakash
Iype, Eldhose
Mir, Nisar A
Choudhary, Sachin
Sharma, Devinder Kumar
Kant, Rajni
Kumar, Indresh
description A pot-economic method for the enantio- and diastereoselective synthesis of a [2.2.2] azabicyclic isoquinuclidine system is developed. This protocol involves the proline-catalyzed direct Mannich reaction-cyclization/IBX-mediated site-selective oxidation/NaBH4-reduction sequence between glutaraldehyde and imines to generate in situ chiral 1,2-DHPs, followed by the diastereoselective Diels–Alder reaction with N-aryl maleimides furnishing isoquinuclidines in overall five steps. A variety of isoquinuclidines having five-contiguous chiral centers, including an all-carbon quaternary, were prepared with high yields (up to 78%) and excellent stereoselectivity (>50:1 dr, and up to >99:1 er). DFT calculations support the observed high stereoselective reaction outcome.
doi_str_mv 10.1021/acs.joc.9b01865
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title Enantio- and Diastereoselective Two-Pot Synthesis of Isoquinuclidines from Glutaraldehyde and N‑Aryl Imines with DFT Calculations
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