Lewis acids catalytic asymmetric 1,3-dipolar cycloadditions

Recent work has focused on developing catalytically controlled asymmetric 1,3-dipolar cycloadditions of cyclic nitrones such as 2,3,4,5-tetrahydropyridine IV-oxide 174. The Lewis acid iron complex 181 catalyzes the cycloaddition of 2,3,4,5-tetrahydropyridine jV-oxide 174 with methacrolein to give (3A,5A)-isoxazolidine 182 in good yield and high enantiomeric selectivity (Scheme 48) <2002JA4968>. The same catalyst 181 however gave (3R,4A,5R)-isoxazolidine 183 with much lower selectivity when crotonaldehyde was used. 

Taking advantage of the Lewis acidic character of the cationic ruthenium complex 107, catalytic asymmetric 1,3-dipolar cycloadditions of nitrones have been developed [113]. In the presence of 5 mol % of 107, the cycloaddition of 108 with crotonaldehyde afforded an isoxazolidine 109 in 80% yield with 66% ee (Eq. 47). 

The greater part of this chapter is concerned with the Diels-Alder and hetero-Diels-Alder reaction. The asymmetric version of both of these reactions can be catalysed with metal-based Lewis acids and also organocatalysts. The catalytic asymmetric 1,3-dipolar cycloaddition of nitrones and azomethine ylides is also discussed. Again, most success in this area has been achieved using metal-based Lewis acids and the use of organocatalysts is begiiming to be explored. This chapter concludes with a brief account of recent research into the asymmetric [2+2]-cycloaddition, catalysed by enantiomerically pure Lewis acids and amine bases, and also the Pauson-Khand [2- -2- -l] cycloaddition mediated by titanium, rhodium and iridium complexes. 

Very recently, Maruoka reported an alternative catalytic asymmetric [3 + 2] cycloaddition reaction between various nitrones and acrolein catalyzed by the x-oxo-type chiral bis-Ti(IV) oxide, giving rise to the corresponding isoxazolidine derivatives in good yields and high enantioselectivities [177]. This type of titanium Lewis acid has also been used in enantioselective 1,3-dipolar cycloaddition of diazoacetates to various substituted acroleins, affording 2-pyrazolines with a chiral quarternary carbon center (Scheme 14.78) [178]. The products obtained with these methodologies have been applied to the synthesis of natural product and biologically important molecules. 

Several successful chiral catalysts have been reported so far for catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones with oxazolidinone derivatives (Figure 16.3) [27a,b,c] Recently, Kiindig et al. [27] had reported that the single coordination site Fe and Ru transition-metal Lewis acids can efficiently promote enantioselective 1,3-dipolar cycloadditions of nitrones with a,p-unsaturated aldehydes and represent a rapid access to substrates of high synthetic potential. The Fe catalyst (81) was found to be an excellent catalyst for 1,3-dipolar cycloaddition reactions between methacrolein and nitrone (83) (Scheme 16.24, Table 16.5). Isox-azolidine (84a) was formed as a single region- and diastereoisomer in excellent... 

The versatile utility of transition-metal Lewis acids in catalytic organic synthesis has been thereby demonstrated in this decade to show high synthetic performance in a variety of reactions with high stereoselection and enantioselection, for example, for asymmetric Diels-Alder reactions, 1,3-dipolar cycloadditions, and other carbon-carbon or hetero atom bond-formation reactions. We hope that this review will stimulate further developments of this category Lewis acid catalyst and its application in a truly efficient chemical process in the future. 

---