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Atropisomeric Transition State Analogs
Author(s) -
Ritzeler Olaf,
Parel Serge,
Therrien Bruno,
Bensel Nicolas,
Reymond JeanLouis,
Schenk Kurt
Publication year - 2000
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200004)2000:7<1365::aid-ejoc1365>3.0.co;2-x
Subject(s) - atropisomer , chemistry , transition state analog , dihedral angle , transition state , methylene , molecular geometry , ring (chemistry) , axial chirality , stereochemistry , molecule , crystallography , enantioselective synthesis , catalysis , hydrogen bond , organic chemistry , active site
Transition state mimicry is one of the most powerful concepts in enzyme inhibitor design and has led to the development of catalytic antibodies. Transition state analogs are compounds with a fixed shape that resemble the geometry and charge distribution of the transition state of a given reaction. Stabilization of a transition state like conformation is most often achieved by incorporating a ring system into the analog. We show herein that atropisomerism can be used as a new principle for enforcing a transition state like conformation. Atropisomerism relates to the existence of stereoisomers of structurally constrained molecules due to a frozen rotation about a single bond, as for example in binaphthol. The 1‐aminomethylnaphthalene derivative 1 exhibits atropisomerism due to a frozen rotation about the C(1)‐C(methylene) single bond, which holds the dihedral angle θ[C(2)‐C(1)‐C(methylene)‐N] close to 90°. Compound 1 mimics the transition state for hydride transfer between 1,4‐dihydroquinolines 4 and acetone.