Diastereoselective reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane with prochiral ketones using the Ti(OiPr)4/NaBH4 system

A simple and convenient one-pot method for the reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane by prochiral ketones using a Ti(OiPr)4/NaBH4 system to obtain the corresponding alkyl amine derivatives in 76–95% yields with good diastereoselectivity (dr = up to 23:1:1) is reported.

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(1R,2R,1′R,1′′R)-N,N′-Di(1-phenylethyl)-1,2-cyclohexanediamineC22H30N2[α]D25=-40.4 (c 1.1, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(4-nitrophenyl)ethyl]-1,2-cyclohexanediamineC22H28N4O4[α]D25=-21.0 (c 1, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(4-chlorophenyl)ethyl]-1,2-cyclohexanediamineC22H28Cl2N2[α]D25=-17.5 (c 1, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di(1,2,3,4-tetrahydro-1-naphthalenyl)-1,2-cyclohexanediamineC26H34N2[α]D25=-115.1 (c 1, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(2-thienyl)ethyl]-1,2-cyclohexanediamineC18H26N2S2[α]D25=-27.9 (c 1, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(2-naphthyl)ethyl]-1,2-cyclohexanediamineC30H34N2[α]D25=-9.1 (c 0.5, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(4-methylphenyl)ethyl]-1,2-cyclohexanediamineC24H34N2[α]D25=-29.2 (c 1.2, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)

(1R,2R,1′R,1′′R)-N,N′-Di[1-(4-methoxyphenyl)ethyl]-1,2-cyclohexanediamineC24H34N2O2[α]D25=+10.7 (c 0.6, CHCl3)Source of chirality: (R,R)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R,1’R,1’’R)