Highly diastereoselective allylation and reduction of chiral camphor-derived α-ketoamides

The diastereoselective allylation and reduction of camphor-derived α-ketoamides to give optically enriched α-hydroxyl amides with high to excellent stereoselectivities are described. Allylation was carried out using allyltributylstannane in the presence of a stoichiometric amount of a Lewis acid to afford the desired homoallylic alcohols in relatively high chemical yields (up to 98%) and stereoselectivities (up to 98% de). Diastereoselective reductions were performed with the relatively bulky hydride K-Selectride at −78 °C to give the corresponding α-hydroxy amides in excellent chemical yields (up to 98%) and stereoselectivities (up to 98% de). The absolute configuration of the new stereogenic center of the major diastereomer was established by X-ray crystallographic analysis. Finally, stereochemical induction and the Lewis acid dependent reversal of stereoselectivity is described.

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1-(10,10-Dimethyl-2-oxo-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]dec-4-yl)-2-phenyl-ethane-1,2-dioneC24H24N2O3[α]D27=-144.8 (c 1, CHCl3)

1-(10,10-Dimethyl-2-oxo-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]dec-4-yl)-propane-1,2-dioneC19H22N2O3[α]D27=-52.3 (c 1, CHCl3)

1-(10,10-Dimethyl-2-oxo-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]dec-4-yl)-butane-1,2-dioneC20H24N2O3[α]D27=-55.7 (c 1, CHCl3)

1-(10,10-Dimethyl-2-oxo-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]dec-4-yl)-2-thiophen-2-yl-ethane-1,2-dioneC22H22N2O3S[α]D27=-268.9 (c 1, CHCl3)

4-(2R)-(Hydroxy-2-phenyl-pent-4-enoyl)-10,10-dimethyl-3-(toluene-4-sulfonyl)-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC28H32N2O5S[α]D27=+142.0 (c 1, CHCl3)

4-(2S)-(Hydroxy-2-phenyl-pent-4-enoyl)-10,10-dimethyl-3-(toluene-4-sulfonyl)-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC28H32N2O5S[α]D27=-71.3 (c 1, CHCl3)

4-(2S)-(Hydroxy-2-phenyl-acetyl)-10,10-dimethyl-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC24H26N2O3[α]D22=-11.5 (c 1, CHCl3)

4-(2S)-(Hydroxy-propionyl)-10,10-dimethyl-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC19H24N2O3[α]D22=-67.1 (c 1, CHCl3)

4-(2S)-(Hydroxy-butyryl)-10,10-dimethyl-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC20H26N2O3[α]D22=-27.1 (c 1, CHCl3)

4-(2R)-(Hydroxy-2-thiophen-2-yl-acetyl)-10,10-dimethyl-3-phenyl-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-oneC22H24N2O3S[α]D22=-10.2 (c 1, CHCl3)