Evaluation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol for catalytic asymmetric addition of organozinc reagents to aldehydes.
A facile and practical approach to preparation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was developed from cheap and easily available l-(+)-methionine. Synthetic highlights include the three-step, one-pot construction of the chiral azetidine ring and the development of an improved one-step procedure for the synthesis of the key intermediate l-2-amino-4-bromobutanoic acid. Enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was evaluated for catalytic asymmetric addition of organozinc reagents to aldehydes. The asymmetric ethylation, methylation, arylation, and alkynylation of aldehydes achieved enantioselectivity of up to 98.4%, 94.1%, 99.0%, and 84.6% ee, respectively, in the presence of a catalytic amount of chiral N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol. Our results demonstrated further that the four-membered heterocycle-based backbone was a good potential chiral unit for the catalytic asymmetric induction reaction, and the hindrance of the bulky ferrocenyl group, compared to a phenyl group, played an important role in the enantioselectivities. A possible transition for the catalytic asymmetric addition has been proposed on the basis of the crystal structure of the chiral ligand 3b including two HOAc molecules and previous studies.
Wang
Min-Can
MC
Department of Chemistry and Henan Key Laboratory of Chemical Biology and Organic Chemistry, Zhengzhou University, Zhengzhou, Henan 450052, PR China. wangmincan@zzu.edu.cn
Zhang
Qing-Jian
QJ
Zhao
Wen-Xian
WX
Wang
Xiao-Dan
XD
Ding
Xue
X
Jing
Tao-Tao
TT
Song
Mao-Ping
MP
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D001547:Benzaldehydes / Q000737:chemistry*; D002384:Catalysis; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D001547:Benzaldehydes; D005296:Ferrous Compounds; D008024:Ligands; C527333:N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol; D009942:Organometallic Compounds; C511262:dimethylzinc