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Chemoselectivity as a Delineator of Cuprate Structure in Catalytic 1,4‐Addition of Diorganozinc Reagents to Michael Acceptors
Author(s) -
Welker Matthias,
Woodward Simon,
Veiros Luis F.,
Calhorda Maria José
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903310
Subject(s) - chemistry , dabco , chemoselectivity , trifluoromethanesulfonate , medicinal chemistry , reactivity (psychology) , catalysis , octane , acetal , stereochemistry , organic chemistry , medicine , alternative medicine , pathology
Reaction of the cyclic thioacetal (RS) 2 CHCHO [R=1/2×(CH 2 ) 3 ] with HCCCOMe, followed by treatment with TsCl/DABCO (Ts=tosyl, DABCO=1,4‐diazabicyclo[2.2.2]octane) affords the mono‐protected 1,4‐benzoquinone dithioacetal. The reactivity of this SR‐protected 1,4‐benzoquinone has been compared with the behavior of the analogous OR‐protected acetal in copper‐catalyzed additions of ZnMe 2 by using chiral phosphoramidite ligands. The activation energy for 1,4‐methylation of the latter OR‐acetals with ZnMe 2 (>95 % ee ) has been determined for two CuX 2 pre‐catalysts (X=OAc, 12.2 kcal mol −1 ; X=OTf, 6.7 kcal mol −1 ; Tf=triflate). The dithioacetal SR aromatizes in the presence of Cu I /ZnMe 2 giving 1,4‐HOC 6 H 4 S(CH 2 ) 3 SMe through CS bond formation. The disparate behavior of these two very closely related substrates is in accordance with the formation of closely related cuprate intermediates that were optimized by DFT calculations, supporting the synthetic and kinetic studies and thus defining the mechanisms of both pathways.