Stereoselective divergent synthesis of 1,2-aminoalcohol-containing heterocycles from a common chiral nonracemic building block

γ-N,N-Dibenzylamino-β-hydroxysulfoxide 1 proved to be an excellent chiral building block for the synthesis of a range of 1,2-amino alcohol-containing heterocycles. Thus, 1 was converted into 4,5-disubstuted oxazolidin-2-one 4 and aminoepoxides 2 and 3. Aminoepoxide 2 proved to be an excellent precursor to access oxazolidin-2-one 5 and azetidin-3-ol 6. Finally, 2 was used as a key intermediate that allowed the development of a divergent strategy to access cis-2-methyl-6-substituted piperidin-3-ol alkaloids. (+)-Deoxocassine 7 and a C-6 ethyl analogue 8 were prepared to illustrate this approach and to demonstrate that this strategy should be adaptable to the production of other members of this alkaloid family.

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(2R,1′S)-2-[1-(N-Benzyl-N-methylamino)ethyl]oxiraneC12H17NO[α]D25 = +12 (c 1, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,1′S)

(4S,5R)-3-Benzyl-4-methyl-5-((p-tolylthio)methyl)oxazolidin-2-oneC19H21NO2S[α]D25 = +20.6 (c 0.97, CHCl3)Source of chirality: the precursorAbsolute configuration: (4S,5R)

(4S,5S)-3-Benzyl-5-(hydroxymethyl)-4-methyloxazolidin-2-oneC12H15NO3[α]D25 = +30 (c 1.05, Me2CO)Source of chirality: the precursorAbsolute configuration: (4S,5S)

(2S,3S)-1-Benzyl-2-methylazetidin-3-olC11H15NO[α]D25 = +44.6 (c 0.83, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S)

(2S,3S,6R)-6-Dodecyl-2-methylpiperidin-3-ol ((+)-deoxocassine)C18H37NO[α]D25 = +11.6 (c 0.95, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S,6R)

(2S,3S,6R)-6-Ethyl-2-methylpiperidin-3-olC8H17NO[α]D25 = +8.8 (c 1.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S,6R)

(S)-3-(Dibenzylamino)butan-2-oneC18H21NO[α]D25 = −52.5 (c 2.95, CHCl3)Source of chirality: the precursorAbsolute configuration: 3S

(2S,3S)-3-(Dibenzylamino)butan-2-olC18H23NO[α]D25 = +71 (c 1.8, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S)

(SR,2R,3S)-N,N-Dibenzyl-2-(methoxymethoxy)-1-(p-tolylsulfinyl)butan-3-amineC27H32NSO3[α]D25 = +7.5 (c 1.05, CHCl3)Source of chirality: the precursorAbsolute configuration: (SR,2R,3S)

(SR,2R,3S)-N-Benzyl-2-(methoxymethoxy)-1-(p-tolylsulfinyl)butan-3-amineC20H27NSO3[α]D25 = +83 (c 0.96, CHCl3)Source of chirality: the precursorAbsolute configuration: (SR,2R,3S)

(2R,3S)-3-(Benzylamino)-1-(p-tolylthio)butan-2-olC18H23NOS[α]D25 = −6.3 (c 0.95, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)

((2R,3S)-1-Benzyl-3-methylaziridin-2-yl)methanolC11H15NO[α]D25 = +13 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)

(6S,7S)-7-(Dibenzylamino)-6-hydroxyoctan-3-oneC22H29NO2[α]D25 = +30.4 (c 0.92, CHCl3)Source of chirality: the precursorAbsolute configuration: (6S,7S)

(5S,6S)-6-(Dibenzylamino)-5-hydroxyheptan-2-oneC21H27NO2[α]D25 = +26 (c 1, CHCl3)Source of chirality: the precursorAbsolute configuration: (5S,6S)

(2S,3S)-2-(Dibenzylamino)hept-6-en-3-olC21H27NO[α]D25 = +52.5 (c 0.80, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S)

(2S,3S,9S,10S)-2,10-Bis-(dibenzylamino)-3,9-dihydroxyundecan-6-oneC39H48N2O3[α]D25 = −37.5 (c 0.39, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S,9S,10S)

(2S,3S)-N,N-Dibenzyl-3-(methoxymethoxy)hept-6-en-2-amineC23H31NO2[α]D25 = +19 (c 0.58, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,3S)

(5S,6S)-6-(Dibenzylamino)-5-(methoxymethoxy)heptan-2-oneC23H31NO3[α]D25 = +14 (c 0.96, CHCl3)Source of chirality: the precursorAbsolute configuration: (5S,6S)

(SS,3R)-3-(Dibenzylamino)-1-(p-tolylsulfinyl)butan-2-oneC25H27NSO2[α]D25 = −13.7 (c 1.02, Me2CO)Source of chirality: the precursorAbsolute configuration: (SS,3R)