A convenient synthesis of new diamine, amino alcohol and aminophosphines chiral auxiliaries based on limonene oxide

A strategy for the synthesis of new chiral auxiliaries based upon vicinal diamines, amino alcohols and aminophosphines, obtained from limonene oxide, has been developed. The methodology allows the preparation of (1R,2R,4S)-1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diamine starting from a commercially available mixture of cis/trans (4S)-(−)-limonene oxides, through a stereoconvergent synthetic sequence. The process starts from an inexpensive naturally occurring material, is amenable to scale-up and allows easy access to highly useful enantiopure building blocks and ligands, employed in asymmetric catalysis.

Figure optionsDownload as PowerPoint slide

(1R,2R,4S)-2-Azido-1-methyl-4-(prop-1-en-2-yl)cyclohexanolC10H17N3OEe = 98%[α]D20=-107.55 (c 1.1, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)

(1R,2R,5S)-2-Azido-2-methyl-5-(prop-1-en-2-yl)cyclohexanolC10H17N3OEe = 98%[α]D20=-75.5 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,5S)

(1S,4S,6R)-1-Methyl-4-(prop-1-en-2-yl)-7-aza-bicyclo-[4.1.0]heptanesC10H17NEe = 98%[α]D20=-40.1 (c 1.9, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1S,4S,6R)

(1R,4S,6S)-Methyl-4-(prop-1-en-2-yl)-7-aza-bicyclo-[4.1.0]heptanesC10H17NEe = 98%[α]D20=-88.3 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,4S,6S)

(1R,2R,5S)-2-Azido-2-methyl-5-(prop-1-en-2-yl)cyclohexanamineC10H18N4Ee = 98%[α]D20=-58.3 (c 1.8, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,5S)

(1R,2R,4S)-2-Azido-1-methyl-4-(prop-1-en-2-yl) cyclohexanamineC10H18N4Ee = 98%[α]D20=-96.8 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)

(1R,2R,4S)-1-Methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diamineC10H20N2Ee = 98%[α]D20=-28.5 (c 0.4, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)

(1R,2R,4S)-1-Methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diamine dioxalateC14H24N2O8Ee = 98%[α]D20=-76.2 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)

(1R,2R,4S)-2-Amino-1-methyl-4-(prop-1-en-2-yl)cyclohexanolC10H19NOEe = 98%[α])D20=-14.6 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)

(1R,2R,5S)-2-Amino-2-methyl-5-(prop-1-en-2-yl)cyclohexanolC10H19NOEe = 98%[α])D20=-17 (c 1.2, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,5S)

(1S,1′S,2R,2′R,4S,4′S)-2,2′-Azanediylbis(1-methyl-4-(prop-1-en-2-yl)cyclohexanolC20H35NO2Ee = 98%[α])D20=-46.8 (c 1.4, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2S,5S)

Diethyl 2-((1R,2R,5S)-2-hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclohexylamino) ethylphosphonateC16H32NO4PEe = 98%[α])D20=-28.0 (c 1.1, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,5S)

Diethyl 2-((1R,2R,5S)-2-amino-2-methyl-5-(prop-1-en-2-yl)cyclohexylamino) ethylphosphonateC16H33N2O3PEe = 98%[α])D20=-24.0 (c 0.7, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,5S)

Tetraethyl 1,2-((1R,2R,4S)-1-methyl-4-(prop-1-en-2-yl)cyclohexyldiamino)-N1,N2-diethyl-phosphonateC22H46N2O6P2Ee = 98%[α])D20=-20.5 (c 0.6, CHCl3)Source of chirality: (−)-(S)-limonene oxideAbsolute configuration: (1R,2R,4S)