Enantioselective Allylation of Aldehydes Catalyzed by Diastereoisomeric Bis(tetrahydroisoquinoline) N,N′‐Dioxides

Abstract

Enantioselective allylation of aromatic and α,β‐unsaturated aldehydes with allyltrichlorosilane catalyzed by two diastereoisomeric (R,Rax,R)‐ and (R,Sax,R)‐bis‐1,1′‐[5,6,7,8‐tetrahydro‐3‐(tetrahydrofuran‐2‐yl)isoquinoline] N,N′‐dioxideswas studied. The course of the reaction was profoundly influenced by the chosen solvent. The (R,Sax,R) catalyst efficiently promoted the reaction in THF with enantioselectivity up to 96 %. On the other hand, the allylation of aromatic aldehydes in the presence of the (R,Rax,R) catalyst proceeded only in MeCN (up to 67 % ee), and the level of asymmetric induction was strongly influenced by the presence of electron‐donating and ‐accepting groups in the aldehyde. The allylation of α,β‐unsaturated aldehydes proceeded only in dichloromethane (enantioselectivity up to 68 %).

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

“…Interestingly, allylation experiments have shown that the N , N′ ‐dioxide catalysts 4 and 5 , developed in this laboratory [it should be appreciated that their design was inspired by the elegant synthesis and use of QUINOX (a mono N ‐oxide containing an element of axial chirality) by Kočovský and Malkov] give the best results in terms of asymmetric induction and yields in THF and other nonpolar solvents. The R ‐catalysts in this instance give rise to homoallylic R ‐alcohols, and the S ‐catalysts give rise to homoallylic S ‐alcohols.…”

Development of Quantum Chemical Method to Calculate Half Maximal Inhibitory Concentration (IC50)

“…The use of ( R,S ) ‐1 provided the ( S )‐ 4 with excellent enantioselectivity in THF of 97% and 96% ee at −78 °C and −40 °C, respectively (entries 5 and 6). Not surprisingly,18a,c,d,h the reactions carried out in dichloromethane furnished the homoallyl alcohols with opposite configurations: ( R,R )‐ 1 gave ( S )‐ 4 and ( R,S ) ‐1 gave ( R )‐ 4 with significantly lower asymmetric inductions in the range of 18–53% ee (entries 3, 4, 7, and 8).…”

Tetrahydroisoquinoline‐Based N‐Oxides as Chiral Organocatalysts for the Asymmetric Allylation of Aldehydes

“…It has been shown that the appropriate choice of solvent is crucial for asymmetric induction, rate, and yield of the allylation reaction 21. Therefore, catalyst 8 was tested in the most common solvents used for this type of asymmetric reaction (Table 2).…”