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Tunable Bifunctional Phosphine–Squaramide Promoted Morita–Baylis–Hillman Reaction of N ‐Alkyl Isatins with Acrylates
Author(s) -
Dong Ze,
Yan Chao,
Gao Yongzhi,
Dong Chune,
Qiu Guofu,
Zhou HaiBing
Publication year - 2015
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201500110
Subject(s) - squaramide , chemistry , bifunctional , isatin , acrylate , baylis–hillman reaction , phosphine , alkyl , electrophile , enantioselective synthesis , yield (engineering) , organic chemistry , organocatalysis , medicinal chemistry , catalysis , polymer , materials science , monomer , metallurgy
A series of highly tunable bifunctional phosphine‐squaramide H‐bond donor organocatalysts 6 has been synthesized from inexpensive and commercially available β ‐amino alcohols in moderate yields. Catalyst 6 f can efficiently promote the asymmetric Morita–Baylis–Hillman (MBH) reaction of N ‐alkyl isatins with acrylate esters providing the chiral 3‐substituted 3‐hydroxy‐2‐oxindoles in good yields and enantioselectivities (up to 93 % yield and 95 % ee ), in which the challenging substrate tert ‐butyl acrylate 9 d , provided the best ee value to date. Moreover, this methodology was applied successfully in the synthesis of chiral cyclic spiropyrrolizidineoxindole and γ ‐butyrolactone derivatives without enantioselectivity deterioration. The possible mechanism of this MBH reaction was also investigated by 31 P NMR, ESI‐MS and KIE studies. The KIE experiments show that the electrophilic addition of N ‐methyl isatin to the complex of acrylate ester and phophine‐squaramide is the rate‐determing step of the asymmetric MBH reaction.