Diels-Alder reaction nonracemic

Several attempts have been made to find chiral dienes yielding adducts with high diastereoselec-tivity in the noncatalyzed Diels-Alder reaction. Nonracemic chiral esters or amides of pentadienoic acid 2 are reacted under high pressure with benzoquinone (1) giving a d.r. [( R,6R,7R)/ (1S,6S,7S)] not greater than 75 2s1. 

This Diels-Alder reaction proceeds in an enantioselective fashion in the presence of chiral, nonracemic Lewis acid catalysts. 2-Pyridinecarbaldehyde and 3-pyridinecarbaldehyde undergo high-yielding addition with Danishefsky s diene in the presence of [(f )-BINOL]2-Ti(OPr )4 complex in 99% and 98% ee, respectively <2005T5822>. 

An interesting approach to cyclophelitol (1) is its synthesis via the nonracemic Diels-Alder reaction to form the scaffold of cyclophelitol as performed by Schlessinger s group, shown... 

Case Study (+)-Estrone 24. The Dane-style estrone synthesis provides a classic example of stereoselective access to an envisaged target molecule. The Diels-Alder reactions between 14 and 15a or 19a are chirogenic71 reaction steps or, put another way, the enantioselective access to the Diels-Alder adducts can already be set at this stage. This requires, for example, the participation of a nonracemic Lewis acid with the right sense of chirality. In the presence of a Ti-TADDOLate [42], cycloadduct 20a was thus obtained from the Dane diene 14 and the bidentate dienophile 19a and was further transformed via 23 into (+)-estrone 248) [33d]. 

Independently, Koizumi et al. also reported [160] the use of nonracemic 3-p-tolylsulfinylacrylates as dienophiles in highly diastereoselective Diels-Alder reactions. The functionalized bicyclo[2.2.1]heptane derivatives such as (186), obtained by asymmetric Diels-Alder cycloaddition of ethyl p-tolylsulfinylmethylenepropionate with cyclopentadiene, have been used as intermediates for the synthesis of bicyclic sesquiterpenes such as (+)-epi-P-santalene (187) [161,162] (Scheme 5.61). 

The first example of an intramolecular asymmetric Diels-Alder reaction of a diene bearing an optically active sullinyl group has recently been reported [195]. The reaction of the a-keto-a,P-unsaturated sulfoxide (258) in the presence of various monodentate Lewis acids (see Table 5.8) gave the nonracemic hetero-... 

Fig, 7. Collection of building blocks A (achiral) and D (chiral nonracemic), intermediates AD and AD , and main component of Diels/Alder reaction with steroid skeleton ABCD. 

Fig. 24. Enantioselective verification of the chirogenic Diels/Alder reaction of the Dane diene 1 and 2 in the presence of a chiral-nonracemic Ti-complex.

The normal demand hetero Diels-Alder cycloaddition between nitroso reagents 171 and dienes 172 leads to the formation of 3,6-dihydro-1,2-oxazines 173 via the concomitant stereoselective formations of a C—N and a C O bonds (Scheme 41.36). Several nitroso dienophiles like the a-chloronitroso, arylnitroso, or acylnitroso compounds are known to react efficiently in cycloadditions. Chiral nonracemic chloronitroso and acylnitroso compounds have been developed to achieve diastereoselective nitroso Diels-Alder reactions, and recently Yamamoto and co-workers reported on the first enantioselective-catalyzed cycloaddition with a pyridylnitroso dienophile. ° ... 

The D-fructose-derived, chiral, nonracemic l,3-oxazin-2-one derivative 260 exerted smooth stereocontrol, resulting in high levels of asymmetric induction and good chemical yields in various synthetic transformations. The chiral fragments 256 and 261 formed in the aldol or a-bromination reactions of the A -propionyl derivative 257 could easily be removed from the parent auxiliary by mild hydrolysis (Scheme 48). The Diels-Alder cyloadditions of the A -acryloyl and A -cinnamoyl derivatives of 260 were also characterized by excellent diasterofacial selectivity <1998T9765>. 

Nonracemic a,P-unsaturated p-tolylsulfoxide dienophiles bearing an electron-withdrawing group in the a-position have been employed successfully in Diels-Alder cycloadditions [28,29,94,133], although less frequently than their 3-substituted counterparts. Koizumi and coworkers have reported the use of optically active 2-p-tolylsulfinylacrylate (188) as a chiral dienophile which exhibits high reactivity and diastereoselectivity in cycloaddition reactions with anthracene and cyclopentadiene (Scheme 5.62), affording cycloadducts (189) and (190),... 

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