New chiral iodooxazoline catalysts for the I(III)-mediated α-tosyloxylation of ketones: refining the stereoinduction model

A new family of iodooxazoline catalysts, derived from widely available chiral ketones (menthone and camphor), was developed to promote the iodine(III)-mediated α-tosyloxylation of ketone derivatives. The reaction conditions to achieve the direct formation of the oxazoline moieties from the corresponding aminoalcohols and an aldehyde were explored and optimized. These catalysts were tested for the α-tosyloxylation of propiophenone and led to new information on the stereoinduction process. The results demonstrate that modulation of the steric hindrance around the iodane center is critical to obtain good activity. Additionally, from the selectivities observed, a preliminary predictive model is proposed.

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(5R,6R,9R)-2-(2-Iodo-3-methylphenyl)-6-isopropyl-9-methyl-1-oxa-3-azaspiro[4.5]dec-2-eneC19H26INO[α]D25=-18.5 (c 0.97, CHCl3)Source of chirality: Menthone ((2S,5R)-2-isopropyl-5-methylcyclohexanone)Absolute configuration: (5R,6R,9R)

(5R,6S,9R)-2-(2-Iodo-3-methylphenyl)-9-methyl-6-(2-phenylpropan-2-yl)-1-oxa-3-azaspiro[4.5]dec-2-eneC25H30INO[α]D25=-18.2 (c 0.97, CHCl3)Source of chirality: Pulegone ((R)-5-methyl-2-(1-methylethylidine)cyclohexanone)Absolute configuration: (5R,6S,9R)

(5S,6S,9R)-2-(2-Iodo-3-methylphenyl)-6-isopropyl-9-methyl-1-oxa-3-azaspiro[4.5]dec-2-eneC19H26INO[α]D25=-12.7 (c 0.32, CHCl3)Source of chirality : Menthone ((2S,5R)-2-isopropyl-5-methylcyclohexanone)Absolute configuration: (5S,6S,9R)

(1R,2S,4R)-2′-(2-Iodo-3-methylphenyl)-1,7,7-trimethyl-4′H-spiro[bicyclo[2.2.1]heptane-2,5′-oxazole]C19H24INO[α]D25=-11.8 (c 0.54, CHCl3)Source of chirality : Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one)Absolute configuration: (1R,2S,4R)

(1R,2R)-2′-(2-Iodo-3-methylphenyl)-1,7,7-trimethyl-4′H-spiro[bicyclo[2.2.1]heptane-2,5′-oxazole]C19H24INO[α]D25=-31.9 (c 1.15, CHCl3)Source of chirality : Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one)Absolute configuration: (1R,2R)

(3aS,4R,7S,7aR)-2-(2-Iodo-3-methylphenyl)-8,8-dimethyl-3a,4,5,6,7,7a-hexahydro-4,7-methanobenzo[d]oxazoleC18H22INO[α]D25=-14.6 (c 1.01, CHCl3)Source of chirality : Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one)Absolute configuration: (3aS,4R,7S,7aR)