Approach to a better understanding and modeling of (S)-dihydrofuran-2-yl, (S)-tetrahydrofuran-2-yl-, and furan-2-yl-β-dialkylaminoethanol ligands for enantioselective alkylation

This paper outlines our efforts to study the influence of an oxygen atom adjacent to the stereogenic center of β-aminoalcohol derivatives used as ligands for catalysts in the asymmetric alkylation of aldehydes. Thirty-four enantiomerically pure (S)-dihydrofuran-2-yl, (S)-tetrahydrofuran-2-yl-, and furan-2-yl-β-dialkylamino alcohols have been prepared from 1,4:3,6-dianhydromannitol, 1,4:3,6-dianhydrosorbitol, and aminoacids, and then have been evaluated as ligands for the enantioselective addition of diethylzinc to benzaldehyde. Attention has been focused on the structural features governing the extent of chiral induction, the reaction rate, and the chemical yield of 1-phenyl-1-propanol which has been promoted by this wide collection of β-dialkylamino alcohols.

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(S)-2-[(S)-2,5-Dihydrofuran-2-yl]-2-(dimethylamino)-ethanolC8H15NO2Ee = 100%[α]D21=-114.8 (c 1.70, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (S,S)

(R)-2-[(S)-2,5-Dihydrofuran-2-yl]-2-(dimethylamino)-ethanolC8H15NO2Ee = 100%[α]D21=-92.7 (c 1.56, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(S)-2-(Dibutylamino)-2-[(S)-2,5-dihydrofuran-2-yl]ethanolC14H27NO2Ee = 100%[α]D24=-135.5 (c 1.04, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (S,S)

(R)-2-(Dibutylamino)-2-[(S)-2,5-dihydrofuran-2-yl]ethanolC14H27NO2Ee = 100%[α]D24=-35.5 (c 1.04, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(S)-2-Amino-2-[(S)-tetrahydrofuran-2-yl]ethanolC14H29NO2Ee = 100%[α]D20=-51.4 (c 2.54, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (S,S)

(R)-2-(Dibutylamino)-2-[(S)-tetrahydrofuran-2-yl]ethanolC14H29NO2Ee = 100%[α]D19=+17.4 (c 1.93, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(S)-1-[(S)-2,5-Dihydrofuran-2-yl]-2-(dimethylamino)ethanolC8H15NO2Ee = 100%[α]D20=-146.9 (c 1.46, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (S,S)

(R)-1-[(S)-2,5-Dihydrofuran-2-yl]-2-(dimethylamino)ethanolC8H15NO2Ee = 100%[α]D23=-83.0 (c 1.05, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(S)-2-(Dibutylamino)-1-[(S)-2,5-dihydrofuran-2-yl]ethanolC14H27NO2Ee = 100%[α]D24=-148.8 (c 1.68, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (S,S)

(R)-2-(Dibutylamino)-1-[(S)-2,5-dihydrofuran-2-yl]ethanolC14H27NO2Ee = 100%[α]D22=-16.1 (c 1.72, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(S)-2-(Dibutylamino)-1-[(S)-tetrahydrofuran-2-yl]ethanolC14H29NO2Ee = 100%[α]D24=-55.4 (c 1.36, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (S,S)

(R)-2-(Dibutylamino)-1-[(S)-tetrahydrofuran-2-yl]ethanolC14H29NO2Ee = 100%[α]D23=+68.0 (c 1.21, CHCl3)Source of chirality: d-sorbitolAbsolute configuration: (R,S)

(R)-2-(Dipropylamino)-1-(furan-2-yl)ethanolC12H21NO2Ee = 100%[α]D21=+95.3 (c 1.29, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-2-(Dibutylamino)-1-(furan-2-yl)ethanolC14H25NO2Ee = 100%[α]D24=+82.1 (c 1.07, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-2-(Di-iso-butylamino)-1-(furan-2-yl)ethanolC14H25NO2Ee = 100%[α]D22=+128.6 (c 1.2, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-2-(Dipentylamino)-1-(furan-2-yl)ethanolC16H29NO2Ee = 100%[α]D23=+78.4 (c 1.15, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-2-(Dihexylamino)-1-(furan-2-yl)ethanolC18H33NO2Ee = 100%[α]D21=+71.0 (c 1.06, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-1-(Furan-2-yl)-2-(pyrrolidin-1-yl)ethanolC10H15NO2Ee = 100%[α]D19=+35.8 (c 0.6, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(R)-2-(Dimethylamino)-1-(furan-2-yl)ethanolC8H10NO2Ee = 100%[α]D21=+44.4 (c 1.05, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(S)-2-(Dibutylamino)-2-(furan-2-yl)ethanolC14H25NO2Ee = 100%[α]D25=-84.0 (c 1.02, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (S)

(R)-2-(Dibutylamino)-2-phenylethanolC16H27NOEe ⩾99%[α]D24=-64.4 (c 1.30, CHCl3)Source of chirality: (R)-(−)-2-phenylglycinol Ee = 99%Absolute configuration: (R)

(S)-2-(Dibutylamino)-1-phenylethanolC16H27NOEe = 98%[α]D22=+103.9 (c 1.05, CHCl3)Source of chirality: (S)-(−)-2-phenyloxirane Ee = 98%Absolute configuration: (S)

(1R,2S)-2-(Dibutylamino)-1-(furan-2-yl)propan-1-olC15H27NO2Ee >99%[α]D21=+15.0 (c 0.4, CHCl3)Source of chirality: l-alanine Ee = 99%Absolute configuration: (1R,2S)

(1S,2S)-2-(Dibutylamino)-1-(furan-2-yl)propan-1-olC15H27NO2Ee ⩾99%[α]D22=+31.9 (c 1.22, CHCl3)Source of chirality: l-alanine Ee = 99%Absolute configuration: (1S,2S)

(1S,2S)-2-(Dibutylamino)-1-(furan-2-yl)-3-methylbutan-1-olC17H31NO2Ee ⩾98%[α]D21=-25.1 (c 1.6, CHCl3)Source of chirality: l-valine Ee ⩾99%Absolute configuration: (1S,2S)

(1R,2S)-2-(Dibutylamino)-1-(furan-2-yl)-3-methylbutan-1-olC17H31NO2Ee ⩾99%[α]D21=+47.3 (c 1.0, CHCl3)Source of chirality: l-valine Ee = 99%Absolute configuration: (1R,2S)

(1S,2S)-2-(Dibutylamino)-1-(furan-2-yl)-3,3-dimethylbutan-1-olC18H33NO2Ee ⩾99%[α]D23=-1.2 (c 2.9, CHCl3)Source of chirality: l-tert-leucine Ee = 99%Absolute configuration: (1S,2S)

(1R,2S)-2-(Dibutylamino)-1-(furan-2-yl)-3,3-dimethylbutan-1-olC18H33NO2Ee ⩾99%[α]D24=+40.6 (c 2.9, CHCl3)Source of chirality: l-tert-leucine Ee = 99%Absolute configuration: (1R,2S)

(1S,2R)-2-(Dibutylamino)-1-(furan-2-yl)-2-phenylethanolC20H29NO2Ee ⩾99%[α]D24=-13.0 (c 1.0, CHCl3)Source of chirality: (R)-(−)-2-phenylglycinol Ee = 99%Absolute configuration: (1S,2R)

(1R,2R)-2-(Dibutylamino)-1-(furan-2-yl)-2-phenylethanolC20H29NO2Ee ⩾99%[α]D24=+3.3 (c 1.4, CHCl3)Source of chirality: (R)-(−)-2-phenylglycinol Ee = 99%Absolute configuration: (1R,2R)