Copper-catalyzed asymmetric conjugate addition of Grignard reagents to 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-1-alkenes

A copper-catalyzed conjugate addition of Grignard reagents to 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-1-alkenes led to 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-2-branched alkanes. Various copper ligands were screened for this reaction. From certain substrates and allylmagnesium bromide, several Josiphos ligands gave low to moderate asymmetric inductions, along with good diastereoselectivity. The stereochemistry of the 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-2-branched alkanes from this reaction was assigned by comparison with the same products from another synthetic route using chiral pool synthesis and stereoselective lithiation methods.

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(R)-3-Methyl-2-phenylbut-3-en-1-olC11H14O[α]D = −55.3 (c 1, CHCl3)Source of chirality: (S)-phenyloxiraneAbsolute chemistry: (2R)

(R)-2-Phenylpent-4-en-1-olC11H14O[α]D = +6.0 (c 1, CHCl3)Source of chirality: (S)-phenyloxiraneAbsolute chemistry: (2R)

(R)-3-Methyl-2-phenylbut-3-enyl N,N-diisopropylcarbamateC18H27NO2[α]D = −36.0 (c 1, CHCl3)Source of chirality: (S)-phenyloxiraneAbsolute chemistry: (2R)

(R)-2-Phenylpent-4-enyl N,N-diisopropylcarbamateC18H27NO2[α]D = +2.7 (c 1, CHCl3)Source of chirality: (S)-phenyloxiraneAbsolute chemistry: (2R)

(1S,2R)-3-Methyl-2-phenyl-1-tosyl-but-3-enyl N,N-diisopropylcarbamateC25H33NO4S[α]D = −35.5 (c 1, CHCl3)Er on C1 = 87.3:12.7, er on C2 = 91.7:8.3Source of chirality: enantioselective deprotonation by (−)-sparteine/s-BuLi on (R)-2-phenylpent-4-enyl N,N-di-isopropylcarbamateAbsolute chemistry: (1S,2R)

(1S,2R)-2-Phenyl-1-tosyl-pent-4-enyl N,N-diisopropylcarbamateC25H33NO4S[α]D = +39.6 (c 1, CHCl3)Er on C1 = 88.8:11.2, er on C2 = 97.2:2.8Source of chirality: diastereoselective deprotonation by TMEDA/s-BuLi on (R)-2-phenylpent-4-enyl N,N-diisopropylcarbamateAbsolute chemistry: (1R,2R)