Imidazolidinones nitrone -cycloadditions

MacMillan s imidazolidinone salts, used successfully in the organocatalysed Diels-Alder reaction (see Section 8.1) also function as effective catalysts in the asymmetric nitrone cycloaddition with simple monodentate dipolarophiles. Thus acrolein (8.63) and crotonaldehyde (8.99) both react with acyclic C-aryl, N-benzyl nitrones and C-aryl N-alkyl nitrones such as (8.198) with high ees ranging from 90 to 99% in the presence of the perchlorate salt of imidazolidinone (8.91). 

In a similar manner to the [4+2] cycloaddition, Benagha has shown that a polyethylene glycol supported imidazolidinone leads to similar levels of enantioselec-tivity in the [3+2] cycloaddition of nitrones with a,P-unsaturated aldehydes when compared to a non-supported catalyst, however, significantly lower chemical yields were obtained, which deteriorated upon catalyst recycling [65]. 

The MacMillan group has also shown that cycloaddition reactions (see also Chapter 8) can be performed highly diastereo- and enantioselectively. The [3+2]-cycloaddition of nitrones and a,/i-un saturated carbonyl compounds in the presence of 20 mol% of a phenylalanine-derived imidazolidinone acid salt led to products with 99% ee [32]. An example of an enantioselective rearrangement reaction (see also Section 13.6) with 99% ee has been reported by the Fu group [33], who used 2 mol% of a planar chiral DMAP derivative as catalyst. 

The first enantioselective organocatalytic 1,3-dipolar cycloaddition of acyclic nitrones with acrolein and crotonal-dehyde has been reported <2000JA9874>. In particular, the reversible formation of iminium ions from a,/3-unsatu-rated aldehydes and the enantiopure imidazolidinone 535 provided ( A-4-formylisoxazolidines in high yields and ees (Equation 86). A polymer-supported version of catalyst 535 was also prepared <2004EJ0567>. The catalytic performance of various chiral pyrrolidinium salts in the cycloaddition of 1-cycloalkene-l-carboxaldehydes was also evaluated <2003EJO2782>. 

A review of recent developments in 1,3-dipolar cycloaddition of nitrones with sila-, thia-, phospha-, and halo-substituted alkenes has been reported. A DFT study of solvent effects on the intermolecular 3-l-2-cycloaddition reaction of norbornadiene with 3,4-dihydroisoquinoline A(-oxide at 398.15 K indicated that the reaction proceeds via a synchronous concerted mechanism. Chiral imidazolidinone salts, in the absence of water, promote the 1,3-dipolar cycloaddition reaction of alanine-derived ketonitrones... 

Sequential 3 -l- 2-cycloaddition/rearrangement reaction of imidazolone nitrones with allenoates has been reported to give methylene imidazolidinones (Scheme 39). ... 

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. 

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