Reaction rate differences between organotrifluoroborates and boronic acids in BINOL-catalyzed conjugate addition to enones

Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.

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Rh-Catalyzed Conjugate Addition of Aryl and Alkenyl Boronic Acids to α-Methylene-β-lactones: Stereoselective Synthesis of trans-3,4-Disubstituted β-Lactones

Organic Letters ◽

10.1021/acs.orglett.7b01994 ◽

2017 ◽

Vol 19 (17) ◽

pp. 4460-4463 ◽

Cited By ~ 6

Author(s):

Christian A. Malapit ◽

Irungu K. Luvaga ◽

Donald R. Caldwell ◽

Nicholas K. Schipper ◽

Amy R. Howell

Keyword(s):

Stereoselective Synthesis ◽

Conjugate Addition ◽

Boronic Acids

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PdII-Catalyzed Conjugate Addition of Boronic Acids to Ketoglutaconic Esters toward the Synthesis of Functionalized Pyridazin-3(2H)-ones with Neuroprotective Activity

European Journal of Organic Chemistry ◽

10.1002/ejoc.201200734 ◽

2012 ◽

Vol 2012 (27) ◽

pp. 5398-5405 ◽

Cited By ~ 2

Author(s):

Silvia Roscales ◽

Andrea Ortega ◽

Sagrario Martín-Aragón ◽

Paloma Bermejo-Bescós ◽

Aurelio G. Csákÿ

Keyword(s):

Conjugate Addition ◽

Boronic Acids ◽

Neuroprotective Activity

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C–H Bond Formation with Boronic Acids and Derivatives by Transition-Metal-Free Conjugate Addition Reactions

Synthesis ◽

10.1055/s-0035-1561444 ◽

2016 ◽

Vol 48 (14) ◽

pp. 2165-2177 ◽

Cited By ~ 5

Author(s):

Aurelio Csákÿ ◽

Francisco Sánchez-Sancho

Keyword(s):

Transition Metal ◽

Bond Formation ◽

Conjugate Addition ◽

Boronic Acids ◽

Addition Reactions ◽

Metal Free

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Strategy of total synthesis based on the use of Rh-catalyzed stereoselective 1,4-addition

Organic & Biomolecular Chemistry ◽

10.1039/c5ob01402f ◽

2015 ◽

Vol 13 (35) ◽

pp. 9168-9175 ◽

Cited By ~ 17

Author(s):

M. Jean ◽

B. Casanova ◽

S. Gnoatto ◽

P. van de Weghe

Keyword(s):

Total Synthesis ◽

Conjugate Addition ◽

Boronic Acids ◽

Rhodium Complexes ◽

Unsaturated Ketones

In 1998, Hayashi and Miyaura reported the first asymmetric conjugate addition of aryl- and alkenyl-boronic acids to α,β-unsaturated ketones using chiral rhodium complexes as catalysts.

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