Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones.
A general and efficient method for the rhodium-catalyzed enantioselective catalytic conjugate addition of organoboronic acids to alpha,beta-unsaturated sulfones is described. The success of the process relies on the use of alpha,beta-unsaturated 2-pyridyl sulfones as key metal-coordinating substrates; typical sulfones such as vinyl phenyl sulfones are inert under the reaction conditions. Among a variety of chiral ligands, Chiraphos provided the best asymmetric induction. This rhodium [Rh(acac)(C2H4)2]/Chiraphos catalyst system has a broad scope, being applicable to the addition of both aryl and alkenyl boronic acids to cis and trans alpha,beta-unsaturated 2-pyridyl sulfones. In most cases, especially in the addition of aryl boronic acids, the reactions take place cleanly and with high enantioselectivity, affording chiral beta-substituted 2-pyridyl sulfones in good yields and enantioselectivities (70-92% ee). The sense and magnitude of this enantioselectivity have been studied by DFT theoretical calculations of the aryl-rhodium insertion step. These calculations strongly support the formation of a five-membered pyridyl-rhodium chelated species as the most stable complex after the insertion into the C=C bond. These highly enantioenriched chiral sulfones are very appealing building blocks in enantioselective synthesis. For instance, the straightforward elimination of the 2-pyridylsulfonyl group by either Julia-Kociensky olefination or alkylation/desulfonylation sequences provides a variety of functionalized chiral compounds, such as allylic substituted alkenes or beta-substituted ketones and esters.
Mauleón
Pablo
P
Departamento de Química OrgAnica, Facultad de Ciencias. Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Alonso
Inés
I
Rivero
Marta Rodríguez
MR
Carretero
Juan C
JC
D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry*
D001897:Boronic Acids; D009942:Organometallic Compounds; D011725:Pyridines; D013450:Sulfones; D012238:Rhodium