Highly diastereoselective Csp₃-Csp₂ Negishi cross-coupling with 1,2-, 1,3- and 1,4-substituted cycloalkylzinc compounds.
Stereoselective functionalizations of organic molecules are of great importance to modern synthesis. A stereoselective preparation of pharmaceutically active molecules is often required to ensure the appropriate biological activity. Thereby, diastereoselective methods represent valuable tools for an efficient set-up of multiple stereocentres. In this article, highly diastereoselective Csp(3) Negishi cross-couplings of various cycloalkylzinc reagents with aryl halides are reported. In all cases, the thermodynamically most-stable stereoisomer was obtained. Remarkably, this diastereoselective coupling was successful not only for 1,2-substituted cyclic systems, but also for 1,3- and 1,4-substituted cyclohexylzinc reagents. The origin of this remote stereocontrol was investigated by NMR experiments and density functional theory calculations. A detailed mechanism based on these experimental and theoretical data is proposed.
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377 München, Germany.
Tobias
T
Thaler
Benjamin
B
Haag
Andrei
A
Gavryushin
Katrin
K
Schober
Evelyn
E
Hartmann
Ruth M
RM
Gschwind
Hendrik
H
Zipse
Peter
P
Mayer
Paul
P
Knochel
D002384:Catalysis; D003516:Cycloparaffins / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
D003516:Cycloparaffins; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D015032:Zinc