Danishefsky-Brassard diene

A80915G is a member of the napyradiomycin family of antibiotics. Its concise total synthesis was published by M. Nakata and co-workers using sequential StiHe cross-coupling of aryl halides with allyltins and the Diels-Alder reaction of a chloroquinone with the Danishefsky-Brassard diene ... 

The same group expanded the scope of the aza-Diels-Alder reaction of electron-rich dienes to Brassard s diene 97 (Scheme 37) [60]. In contrast to Danishefsky s diene, it is more reactive, but less stable. Akiyama et al. found chiral BINOL phosphate (R)-3m (3 mol%, R = 9-anthryl) with 9-anthryl substituents to promote the [4 + 2] cycloaddition of A-arylated aldimines 94 and Brassard s diene 97. Subsequent treatment with benzoic acid led to the formation of piperidinones 98. Interestingly, the use of its pyridinium salt (3 mol%) resulted in a higher yield (87% instead of 72%) along with a comparable enantioselectivity (94% ee instead of 92% ee). This method furnished cycloadducts 98 derived from aromatic, heteroaromatic, a,P-unsaturated, and aliphatic precursors 94 in satisfactory yields (63-91%) and excellent enantioselectivities (92-99% ee). NMR studies revealed that Brassard s diene 97 is labile in the presence of phosphoric acid 3m (88% decomposition after 1 h), but comparatively stable in the presence of its pyridinium salt (25% decomposition after 1 h). This observation can be explained by the fact that the pyridinium salt is a weak Brpnsted acid compared to BINOL phosphate 3m. 

Among the more reactive and synthetically useful dienes are doubly and triply activated alkoxy- and amino-substituted dienes, such as ( )-l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene),( )-l-(dimethylamino)-3-(fert-butyldimethylsilyloxy)-1,3-butadiene (Rawal s diene)-, and 1,3-dimethoxy-l-(trimethylsilyloxy)-1,3-butadiene (Brassard s diene). As illustrated below, the cyclo-addition products arising from these dienes can either be hydrolyzed or treated with fluoride ion to remove the silyl group, which is followed by (3-elimination to provide conjugated cyclohexenones. 

Danishefsky s dienes and Brassard s dienes, with imines provides an efficient route... 

Chiral phosphoric add is also effective for aza-Diels-Alder reactions. Danishefsky s diene underwent aza-Diels-Alder reaction with aldimines by means of 21e in the presence of acetic add to give the cycloadduds with high enantios-eledivities (Equation 10.43) [89]. Brassard s diene also partidpated in the aza-Diels-Alder readion under the influence of 21j to give 5-ladams with excellent enantioselectivities [90]. 

The hetero-Diels-Alder reactions of acyl phosphonates with c-rich dienes, such as Danishefsky s diene and Brassard s diene, produced glycosyl-type phosphonates in moderate to good yields. The indium(III)-catalysed hetero-Diels—Alder reaction of a Brassard-type diene with aliphatic aldehydes produced /l-methoxy-y-methyl-a, -unsaturated (5-lactones in good yields (86%) and with high diastereo- and enantio- 0 selectivities. ... 

Similarly, pyran rings are a common early-stage synthetic intermediate in a variety of syntheses. In Kutay and Gademann s synthesis of anguinomycin C, they prepare the heterocyclic portion of the target by combination an electron-rich diene with an unsaturated aldehyde in the presence of Jacobsen s chromium (III) catalyst. Ghosh used the same asymmetric catalyst to promote the reaction of an aldehyde and an electron-rich diene in his synthesis of brevisamide. Rawal synthesized a pyranone for use in his synthesis of pederin by combination of a chiral dienophile with Danishefsky s diene. In his synthesis of phorboxazole B, Burke treated Brassard diene 119 with chiral aldehyde 118 and a europium catalyst to yield pyranone 120. ... 

The enantioselective hetero-Diels-Alder reaction of siloxydienes, such as Danishefsky s and Brassard s dienes, with imines provides an efficient route for the preparation of functionalized nitrogen-containing heterocycles in optically active forms. Akiyama and coworkers reported the first catalytic enantioselective hetero-Diels-Alder reaction of Danishefsky s diene (21) with aromatic imines 20 using chiral phosphoric acid catalyst la (Scheme 11.7a) [14]. The desired dihydropyridi-nones 22 were obtained in good yields with high enantioselectivities. Notably, the addition of an equimolar amount of acetic acid was effective in improving the enantioselectivity. Akiyama and coworkers also reported an enantioselective... 

Notes See Brassard s. Danishefsky s and Rawal s Diene and for similar reactions different substitution patterns. 

Asymmetric hetero-Diels-Alder reactions of Danishefsky s and Brassard s dienes with aldehydes 07SL2147. 

R] For a review of asymmetric hetero Diels-Alder reactions of Danishefsky s and Brassard s dienes with aldehydes, see Lin, L. Liu, X. Feng, X. Synlett 2007, 2147-2157. 

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