Reversal of Diastereoselection in the Conjugate Addition of Cuprates to Unsaturated Lactams.
We report that the stereochemical outcome of the conjugate addition of organocopper reagents to bicyclic α,β-unsaturated lactams derived from pyroglutaminol is determined by the nature of the aminal group. Bicyclic α,β-unsaturated lactams in which the aminal is derived from a ketone have been found to afford products of syn conjugate addition. By contrast, bicyclic α,β-unsaturated lactams in which the aminal is derived from an aldehyde afford products of anti conjugate addition. These remarkably different results obtained from very similar starting materials are unexpected.
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Stephen W
SW
Wright
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Chulho
C
Choi
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Seungwon
S
Chung
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Brian P
BP
Boscoe
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
Susan E
SE
Drozda
Worldwide Medicinal Chemistry, Pfizer Global Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
James J
JJ
Mousseau
Inflammation & Immunology Research, Pfizer Global Research and Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.
John D
JD
Trzupek
D000447:Aldehydes / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D007769:Lactams / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D007659:Ketones; D007769:Lactams; D011758:Pyrroles; C431590:pyroglutaminol; D003300:Copper