Catalytic Asymmetric 1,3-Dipolar Cycloaddition Reactions

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... 

Iwasa, S., Ishima, Y., Widagdo, H. S., Aoki, K., Nishiyama, H. (2004). Synthesis of novel chiral bis(2-oxazolinyl)xanthene (xabox) ligands and their evaluation in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones with 3-crotonoyl-2-oxazolidinone. Tetrahedron Letters, 45, 2121-2124. 

Although the first metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction involved azomethine ylides, there has not been any significant activity in this area since then. The reactions that were described implied one of more equivalents of the chiral catalyst, and further development into a catalytic version has not been reported. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

Mish, M.R., Gnerra, E.M., and Carreira, E.M., Asymmetric dipolar cycloadditions of Me3SiCHN2. Synthesis of a novel class of amino acids azaprolines, J. Am. Chem. Soc. 119 (35), 8379, 1997. Kim, Y., Singer, R.A., and Carreira, E.M., Total synthesis of macrolactin A with versatile catalytic, enantioselective dienolate aldol addition reactions, Angewandte Chemie-Intemational Edition 37 (9), 1261, 1998. 

MacMillan has described a class of readily available, chiral imidazolidi-nones that act as catalysts in a variety of catalytic asymmetric transformations [89]. The chiral imidazolidinone catalyst 103 was noted to be efficient for the activation of simple a, 5-unsaturated aldehydes towards dipolar cycloaddition reactions via the corresponding iminium intermediate 104 (Scheme 18.20) [90]. With crotonaldehyde (102), the [l,3]-dipolar cycloaddition reaction with nitrone 97 furnished the corresponding endo cycloadduct 105 with high stereoselectivity (endolexo=9A (>, 94% ee). The observed stereoselectivity was consistent with preferential formation of the ( )-isomer 104. 

It has recently been found that Et2Zn promotes the 1,3-dipolar cycloaddition of nitrile oxides to allyl alcohol in the presence of catalytic amounts of diisopropyl tartrate (DIPT). By this method, 2-isoxazlines are obtained in good yields and up to 96% ee (Eq. 8.73).124a A positive nonlinear effect (amplification of ee of the product) has been observed in this reaction. There is an excellent review on positive and negative nonlinear effects in asymmetric induction.124b... 

The development and application of catalytic enantioselective 1,3-dipolar cycloadditions is a relatively new area. Compared to the broad application of asymmetric catalysis in carbo- and hetero-Diels-Alder reactions (337,338), which has evolved since the mid-1980s, the use of enantioselective metal catalysts in asymmetric 1,3-dipolar cycloadditions remained almost unexplored until 1993 (5). In particular, the asymmetric metal-catalyzed reactions of nitrones with alkenes has received considerable attention during the past 5 years. 

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