Chiral Diols

Apart from numerous examples using TADDOLs in metal-catalyzed asymmetric reactions, Rawal recently reported that TADDOLs could be used as Brønsted acid organocatalysts in highly stereoselective hetero-Diels–Alder reactions.¹ The reaction of an electron-rich diene with benzaldehyde using 10 mol % TADDOL (395242) provides the dihydropyrone as a single stereoisomer (Scheme 1).

Scheme 1.

The α-amination of carbonyl compounds has also been accomplished by using the 1-naphthyl TADDOL derivative as a Brønsted acid catalyst (Scheme 2).² The reaction of different enamines with nitrosobenzene gave exclusively the N-regioisomers in a highly enantioselective manner.

Scheme 2.

A highly enantioselective addition of cyclohexenone to different aldehydes (asymmetric Morita–Baylis–Hillman reaction) catalyzed by octahydro-BINOL-derived Brønsted acid (669172) was reported by Schaus (Scheme 3).³ Important for achieving high enantioselectivity were both the partial saturation and substitution at the 3,3’-positions of the BINOL derivative.

Scheme 3.

1. Huang Y, Unni AK, Thadani AN, Rawal VH. 2003. Single enantiomers from a chiral-alcohol catalyst. Nature. 424(6945):146-146. https://doi.org/10.1038/424146a

2. Guo H, Cheng L, Cun L, Gong L, Mi A, Jiang Y. l-Prolinamide-catalyzed direct nitroso aldol reactions of α-branched aldehydes: a distinct regioselectivity from that withl-proline. Chem. Commun..(4):429-431. https://doi.org/10.1039/b514194j

3. McDougal NT, Schaus SE. 2003. Asymmetric Morita-Baylis-Hillman Reactions Catalyzed by Chiral Brønsted Acids. J. Am. Chem. Soc.. 125(40):12094-12095. https://doi.org/10.1021/ja037705w