Jan, 2017
Origin of High Regio-, Diastereo-, and Enantioselectivities in 1,6-Addition of Azlactones to Dienyl N-Acylpyrroles: A Computational Study
JOURNAL OF ORGANIC CHEMISTRY
- ,
- ,
- ,
- ,
- Volume
- 82
- Number
- 1
- First page
- 541
- Last page
- 548
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1021/acs.joc.6b02572
- Publisher
- AMER CHEMICAL SOC
Chiral P-spiro triaminoiminophosphorane (1) was developed to promote the highly regio-, diastereo-, and enantioselective 1,6- and 1,8-additions of azlactones (2 center dot H) to dienyl and trienyl N-acylpyrroles (3 and 4). DFT calculations enabled us to gain deep insight into the whole reaction mechanism as well as the origin of the high regio- and stereoselectivities. The present reaction consists of three steps: (1) formation of the phosphonium-enolate ion-pair complex by deprotonation of 2 center dot H with 1, (2) C-C bond formation of 2 with 3 and 4, and (3) protonation of the resulting enolate anion. The C-C bond formation is irreversible, and the rate- and stereodetermining step. The C-gamma-protonation preferentially proceeds rather than the thermodynamically and kinetically disfavored O- and C-alpha-protonation, respectively. The high regio- and enantioselectivities are mainly attributed to the steric and electronic features of 1 center dot H and 3/4. The hydrogen bonds (NH-O and CH-O) and the attractive CH-pi interaction between 1 center dot H and 2 and 3 play a key role in achieving high stereocontrol. The high regioselectivity is mainly controlled by the structural distortion of 1 center dot H and the disruption of the p-conjugated system of 3 (1,4-system) and 4 (1,4- and 1,6-systems).
- Link information
- ID information
-
- DOI : 10.1021/acs.joc.6b02572
- ISSN : 0022-3263
- Web of Science ID : WOS:000391781900051