Chiral terpene auxiliaries III: spiroborate esters from (1R,2S,3R,5R)-3-amino-apopinan-2-ol as highly effective catalysts for asymmetric reduction of ketones with borane

New spiroborate esters, derived from terpene amino alcohols, (S)-prolinol, and 2-aminoethanol, were employed as catalysts in the borane reduction of acetophenone and other aryl alkyl and halogenated ketones. The corresponding alcohols were obtained in high yields and with enantioselectivities up to 98% ee. The influence of the amino alcohol and the diol moieties of spiroborate on the reaction selectivity was examined. The catalyst load, the nature of the solvent, the borane source, and the reaction conditions were also investigated.

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(1R,2S,3R,5R)-2-(1′,3′,2′-Dioxaborolan-2′-yloxy)-apopinan-3-amineC11H20BNO3Ee = 99%[α]D20 = −23.8 (c 0.5, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,5R)

(1R,2S,3R,5R)-2-(1′,3′,2′-Dioxaborolan-(4′-2,5′-3-(1R,2R,3S,5R)-pinan)-2′-yloxy)-apopinan-3-amineC19H32BNO3Ee = 99%[α]D20 = −20.6 (c 0.6, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,5R)

(1R,2S,3R,5R)-2-(1′,3′,2′-Dioxaborolan-(4′-3,5′-4-(1S,3S,4R,6R)-caran)-2′-yloxy)-apopinan-3-amineC19H32BNO3Ee = 99%[α]D20 = −17.5 (c 0.6, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,5R)

(1R,2S,3R,5R)-2-(1′,3′,2′-Dioxaborolan-(4′-3,5′-4-tetrahydrofuran)-2′-yloxy)-apopinan-3-amineC13H22BNO4Ee = 99%[α]D20 = −28.5 (c 0.6, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,5R)

(1R,2S,3R,5R)-2-(1′,3′,2′-Dioxaborolan-(4′-1,5′-2-cyclopentan)-2′-yloxy)-apopinan-3-amineC14H24BNO3Ee = 99%[α]D20 = −17.0 (c 0.5, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,5R)

(1S,3S,4R,6R)-3-(1′,3′,2′-Dioxaborolan-2′-yloxy)-caran-4-amineC12H22BNO3Ee = 99%[α]D20 = −2.2 (c 0.5, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S,4R,6R)

(1S,2S,3S,4S,5R)-3-(1′,3′,2′-Dioxaborolan-2′-yloxy)-2-methoxy-pinan-4-amineC13H24BNO4Ee = 99%[α]D20 = +33.3 (c 0.6, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,3S,4S,5R)

(S)-2-[(1,3,2-Dioxaborolan-(4-2′,5-3′-(1′S,2′S,3′R,5′S)-pinan)-2-yloxy)-methyl]pyrrolidineC15H26BNO3Ee = 99%[α]D20 = +22.95 (c 0.6, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(1′S,2′S,3′R,5′S)

(S)-2-[(1,3,2-Dioxaborolan-(4-2′,5-3′-(1′R,2′R,3′S,5′R)-pinan)-2-yloxy)-methyl]pyrrolidineC15H26BNO3Ee = 99%[α]D20 = +22.0 (c 0.5, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(1′R,2′R,3′S,5′R)

2-(1,3,2-Dioxaborolan-(4-2′,5-3′-(1′R,2′R,3′S,5′R)-pinan)-2-yloxy)-ethanamineC12H22BNO3Ee = 99%[α]D20 = −26.4 (c 0.5, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (1′R,2′R,3′S,5′R)