| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347735 | Tetrahedron: Asymmetry | 2008 | 7 Pages |
A catalyst composed of (R,R)-MeDuphos and CuBr·SMe2 catalyzes the addition of RMgBr (R = Et, C5H11, Ph) to simple enamides (E)-Me2NCOCHCHR1 (R1 = Me, C5H11) in acceptable yields (50–78%), but with poor to modest enantioselectivities (0–74% ee). By changing the enamide acceptor to the (E)-(Aux)NCOCHCHMe [Aux = from commercial pseudoephedrine, (R,R)-NMeCHMeCHPhOH] a stereochemically enhanced regime could be attained. Structurally diverse RMgBr (R = C5H11, vinyl, allyl, Ph) underwent 1,4-additions in 57–89% de and 88–93% yield. In one case, the resulting enolate could be trapped with allyl bromide.
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(R)-N,N-Dimethyl-3-methyl-pentanamideC8H17NOEe = 64%[α]D = −5.6 (c 1.5, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)
(S)-N,N-Dimethyl-3-ethyl-octanamideC12H25NOEe = 68%[α]D = +1.1 (c 1.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)
(S)-N,N-Dimethyl-3-methyl-octanamideC12H25NOEe = 74%[α]D = +1.0 (c 0.9, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (S)
(3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-3-methylpentanamideC16H25NO2De = 84%, rest (3S)-epimer[α]D = −101 (c 1.26, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrineAbsolute configuration: (3R,1′R,2′R)
(3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-3-methyloctanamideC19H31NO2De = 76%, rest (3S)-epimer[α]D = −88 (c 1.13, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrineAbsolute configuration: (3R,1′R,2′R)
(3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-3-phenylbutanamideC20H25NO2De = 89%, rest (3S)-epimer[α]D = −77 (c 1.25, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrineAbsolute configuration: (3R,1′R,2′R)
(3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-3-methylhex-5-enamideC17H25NO2De = 76%, rest (3S)-epimer[α]D = −94 (c 0.84, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrineAbsolute configuration: (3R,1′R,2′R)
(3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-3-methylpent-4-enamideC16H23NO2De = 57%, rest (3S)-epimer[α]D = −93 (c 1.05, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrineAbsolute configuration: (3R,1′R,2′R)
(2R,3R,1′R,2′R)-N-Methyl-N-(2′-phenyl-2′-hydroxy-1′-methyethyl)-2-allyl-3-methylpentanamideC20H29NO2De = 92%, rest (2R,3S)-enantiomer[α]D = −73 (c 1.05, CHCl3)Source of chirality: diastereoselective addition using (R,R)-(−)-pseudoephidrine, followed by alkylationAbsolute configuration: (2R,3R,1′R,2′R)
