Chiral Unsymmetrically Substituted Bipyridine N,N′‐Dioxides as Catalysts for the Allylation of Aldehydes

Abstract

A series of unsymmetrically substituted diastereoisomeric (Ra,R) and (Sa,R) bipyridine N,N′‐dioxides was synthesized by using oxidative coupling of the corresponding metallated tetrahydroisoquinoline N‐oxides in the presence of iodine. The N,N′‐dioxides contained substituted aryl groups with electron‐donating or electron‐accepting groups in the near vicinity of the N,N′‐dioxide moiety. Their catalytic activity was tested in a series of reactions of allyltrichlorosilane with various substituted benzaldehydes, thiophenecarbaldehyde, and cinnamaldehyde. The reactions proceeded with high enantioselectivities (up to 98 % ee) with catalyst loadings as low as 0.5 mol‐%. Furthermore, allylation reactions of (E)‐3‐iodomethacrylaldehyde were also carried out to give chiral (E)‐1‐iodo‐2‐methylpenta‐1,4‐dien‐3‐ol, a convenient building block for the synthesis of natural products. The allylations proceeded with high enantioselectivities (up to ca. 99 % ee) with a catalyst loading of 2.5 mol‐%.

Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review

“…Gradual increase of catalyst loading showed, that both the yield and enantioselectivity increased up to 74%, 80% ee for 5 mol% of (aR,R)-34a and 90%, 88% ee for 5 mol% of (aS,R)-34a. The allylations of benzaldehyde, p-methoxybenzaldehyde and p-trifluoromethylbenzaldehyde using 34, described in this report, were performed using 0.5 mol% of the catalyst [54]. Comparing them with the same reactions applying 1mol% of the catalyst [36] allows the conclusion that reducing the loading does not affect enantioselectivity.…”

“…The allylation of 4-methoxybenzaldehyde was also performed using (-)-36b and, despite that methoxy group is electron-donating (similar to methyl group), in this case, the obtained product was racemic. Kotora et al synthesized a number of derivatives 34 (see Figure 7), with variously modified aromatic substituents at the 3' position [54]. All these dioxide derivatives have been tested, as Lewis base catalysts, in allylation of aromatic aldehydes (0.5 mol%) in THF and CH2Cl2.…”

“…The predictable utility of the expected product as a chiral building block in the synthesis of natural products [54,55] was the reason for the application of 34a-g in allylation of E-3iodomethacrylaldehyde ( Table 7). For this reaction, the influence of modification of the phenyl group in catalyst turned out to be significant.…”

“…Table 7. Allylation of E-3-iodomethacrylaldehyde catalyzed by 34a-g [54]. Kotora et al synthesized a number of derivatives 34 (see Figure 7), with variously modified aromatic substituents at the 3' position [54].…”

“…Allylation of E-3-iodomethacrylaldehyde catalyzed by 34a-g [54]. Kotora et al synthesized a number of derivatives 34 (see Figure 7), with variously modified aromatic substituents at the 3' position [54]. All these dioxide derivatives have been tested, as Lewis base catalysts, in allylation of aromatic aldehydes (0.5 mol%) in THF and CH 2 Cl 2 .…”