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Enantioselective C-H lactonization of unactivated methylenes directed by carboxylic acids
- Source :
- © Journal of the American Chemical Society, 2019, vol.142, núm. 3, p.1584-1593, Articles publicats (D-Q), DUGiDocs – Universitat de Girona, instname, Journal of the American Chemical Society, Journal of the American Chemical Society, 142(3), 1584. American Chemical Society
- Publication Year :
- 2020
- Publisher :
- American Chemical Society, 2020.
-
Abstract
- The formidable challenges of controlling site-selectivity, enantioselectivity, and product chemoselectivity make asymmetric C-H oxidation a generally unsolved problem for nonenzymatic systems. Discrimination between the two enantiotopic C-H bonds of an unactivated methylenic group is particularly demanding and so far unprecedented, given the similarity between their environments and the facile overoxidation of the initially formed hydroxylation product. Here we show that a Mn-catalyzed C-H oxidation directed by carboxylic acids can overcome these challenges to yield γ-lactones in high enantiomeric excess (up to 99%) using hydrogen peroxide as oxidant and a Brønsted acid additive under mild conditions and short reaction times. Coordination of the carboxylic acid group to the bulky Mn complex ensures the rigidity needed for high enantioselectivity and dictates the outstanding γ site-selectivity. When the substrate contains nonequivalent γ-methylenes, the site-selectivity for lactonization can be rationally predicted on the basis of simple C-H activation/deactivation effects exerted by proximal substituents. In addition, discrimination of diastereotopic C-H bonds can be modulated by catalyst design, with no erosion of enantiomeric excess. The potential of this reaction is illustrated in the concise synthesis of a tetrahydroxylated bicyclo[3.3.1]nonane enabled by two key, sequential γ-C-H lactonizations, with the latter that fixes the chirality of five stereogenic centers in one step with 96% ee Support by the Spanish Ministry of Science (PGC2018-101737-B-I00 to M.C. and J.d.C. grant to G.O., FJCI-2016-30243), and Gen-eralitat de Catalunya (ICREA Academia Award to M.C. and 2014SGR 862), and from EU (MSCA-ITN-2015 Action NoNoMeCat, 675020) is acknowledged
- Subjects :
- Oxidation-reduction reaction
010405 organic chemistry
Chemistry
C-H oxidation
enantioselectivity
catalyst design
organic synthesis
Enantioselective synthesis
General Chemistry
010402 general chemistry
01 natural sciences
Biochemistry
Redox
Combinatorial chemistry
Catalysis
0104 chemical sciences
Settore CHIM/06
Colloid and Surface Chemistry
Reacció d'oxidació-reducció
Product (mathematics)
Taverne
Chemoselectivity
Subjects
Details
- Language :
- English
- ISSN :
- 00027863
- Database :
- OpenAIRE
- Journal :
- © Journal of the American Chemical Society, 2019, vol.142, núm. 3, p.1584-1593, Articles publicats (D-Q), DUGiDocs – Universitat de Girona, instname, Journal of the American Chemical Society, Journal of the American Chemical Society, 142(3), 1584. American Chemical Society
- Accession number :
- edsair.doi.dedup.....4d16660957345766a831ed8d49e2512c