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Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones.
J Org Chem. 2007 Dec 21; 72(26):9924-35.JO

Abstract

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.

Authors+Show Affiliations

Mauleón P
Departamento de Química OrgAnica, Facultad de Ciencias. Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Alonso I
No affiliation info available
Rivero MR
No affiliation info available
Carretero JC
No affiliation info available

MeSH

Boronic AcidsCatalysisModels, ChemicalMolecular StructureOrganometallic CompoundsPyridinesRhodiumStereoisomerismSulfones

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18047369

Citation

Mauleón, Pablo, et al. "Enantioselective Synthesis of Chiral Sulfones By Rh-catalyzed Asymmetric Addition of Boronic Acids to Alpha,beta-unsaturated 2-pyridyl Sulfones." The Journal of Organic Chemistry, vol. 72, no. 26, 2007, pp. 9924-35.
Mauleón P, Alonso I, Rivero MR, et al. Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones. J Org Chem. 2007;72(26):9924-35.
Mauleón, P., Alonso, I., Rivero, M. R., & Carretero, J. C. (2007). Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones. The Journal of Organic Chemistry, 72(26), 9924-35.
Mauleón P, et al. Enantioselective Synthesis of Chiral Sulfones By Rh-catalyzed Asymmetric Addition of Boronic Acids to Alpha,beta-unsaturated 2-pyridyl Sulfones. J Org Chem. 2007 Dec 21;72(26):9924-35. PubMed PMID: 18047369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones. AU - Mauleón,Pablo, AU - Alonso,Inés, AU - Rivero,Marta Rodríguez, AU - Carretero,Juan C, Y1 - 2007/11/30/ PY - 2007/12/1/pubmed PY - 2008/3/26/medline PY - 2007/12/1/entrez SP - 9924 EP - 35 JF - The Journal of organic chemistry JO - J Org Chem VL - 72 IS - 26 N2 - 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. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/18047369/Enantioselective_synthesis_of_chiral_sulfones_by_Rh_catalyzed_asymmetric_addition_of_boronic_acids_to_alphabeta_unsaturated_2_pyridyl_sulfones_ DB - PRIME DP - Unbound Medicine ER -