Construction of a bicyclic beta-benzyloxy and beta-hydroxy amide library through a multicomponent cyclization reaction.
In this manuscript, we describe the synthesis of a bicyclic beta-benzyloxy and beta-hydroxy amide library from cyanohydrin ethers. The benzyloxy amides were prepared through a one-pot sequence of hydrozirconation, acylation, and intramolecular Friedel-Crafts alkylation. Selected benzyl ethers were converted to alcohols by hydrogenolysis in a continuous flow reactor. Chemistry space BCUT metrics and 2D fingerprint similarity calculations showed that these compounds contribute chemical diversity value to existing chemical libraries.
Zhang
Li
L
University of Pittsburgh Center for Chemical Methodologies and Library Development and Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Xiao
Qing
Q
Ma
Chao
C
Xie
Xiang-Qun
XQ
Floreancig
Paul E
PE
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
D000577:Amides; D001643:Bridged Bicyclo Compounds; D004987:Ethers; D009570:Nitriles; D054852:Small Molecule Libraries; C430593:cyanohydrin