Cycloaddition activated dienes with aldehydes

Bednarski, M, Danishefsky, S, Interactivity of chiral catalysts and chiral auxiliaries in the cycloaddition of activated dienes with aldehydes a synthesis of L-glucose, J. Am. Chem. Soc., 108, 7060-7067, 1986. 

In 1984 Danishefsky and Bednarski demonstrated that lanthanide(III) complexes catalyze the cycloaddition of activated dienes with aldehydes. The stereoselectivity increases climatically when using these catalysts. When diene (8), for example, reacts with a variety of aldehydes with Eu(fc )3 as catalyst virtually complete cis (endo) selectivity is observed (Table 6). The aldehydes that function as dienophiles can be aliphatic (acetaldehyde and hexanal) or aromatic (benzaldehyde and furfural). 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

A chiral vanadium complex, bis(3-(heptafluorobutyryl)camphorato)oxovana-dium(IV), can catalyze the cycloaddition reaction of, mainly, benzaldehyde with dienes of the Danishefsky type with moderate to good enantioselectivity [21]. A thorough investigation was performed with benzaldehyde and different activated dienes, and reactions involving double stereo differentiation using a chiral aldehyde. 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

Different main-group-, transition- and lanthanide-metal complexes can catalyze the cycloaddition reaction of activated aldehydes with activated and non-activated dienes. The chiral metal complexes which can catalyze these reactions include complexes which enable substrates to coordinate in a mono- or bidentate fashion. 

Trace amounts of complexes 3 and 20 promote the synthesis of optically pure, multiply functionalized, versatile intermediates such as pyrones or lactones from activated, acid-labile siloxydienes with aldehydes. The reagents typically work under mild conditions and therefore promote the survival of valuable functionality in the dienophile, the diene, and cycloadduct [105-107]. As a consequence this procedure is applied in the total synthesis of various natural products, often requiring an intramolecular Diels-Alder approach [106]. Specific interactivity of the chiral precatalyst Eu(hfc)3 (hfc = 3-(heptafluorpropylhydroxymethylene)-D-camphorate with Danishefsky s diene bearing a chiral auxiliary resulted in cycloaddition products of high diastereofacial excess (95 % eq. (8)) [105]. 

Supported Lewis acids are an interesting class of catalysts because of their operational simplicity, filterability and reusability. The polymer-bound iron Lewis-acid 53 (Figure 3.8) has been found [52] to be active in the cycloadditions of a,/ -unsaturated aldehydes with several dienes. It has been prepared from (ri5-vinylcyclopentadienyl)dicarbonylmethyliron which was copolymerized with divinylbenzene and then treated with trimethylsilyltriflate followed by THF. Some results of the Diels-Alder reactions of acrolein and crotonaldehyde with isoprene (2) and 2,3-dimethylbutadiene (4) are summarized in Equation... 

The cycloadditions of carbonyl compounds with dienes lead to 5,6-dihydro-2//-pyrans. Electron-deficient aldehydes have to be employed in combination with butadienes bearing electron-donating groups. However, using non-activated dienes rate acceleration can be achieved by applying high temperatures, high pressure or Lewis acids. 

More recently, allenes, acetylenes and activated dienes have been added as olefin equivalents, leading to products of more eomplex skeletons. Though the first report on allenic compounds involved in a MBH reaction dates back to the DABCO-catalyzed and butyllithium-promoted aldol condensation of allenic ester with aldehydes reported by Tsuboi et there are very few reports of MBH reactions involving allenoates because they easily undergo cycloaddition reactions under different Lewis bases. For instance, five-membered pyrrolidine... 

Yamamoto et al. were probably the first to report that chiral aluminum(III) catalysts are effective in the cycloaddition reactions of aldehydes [11]. The use of chiral BINOL-AlMe complexes (R)-S was found to be highly effective in the cycloaddition reaction of a variety of aldehydes with activated Danishefsky-type dienes. The reaction of benzaldehyde la with Danishefsky s diene 2a and traws-l-methoxy-2-methyl-3-(trimethylsilyloxy)-l,3-pentadiene 2b affords cis dihydropyrones, cis-3, as the major product in high yield with up to 97% ee (Scheme 4.6). The choice of the bulky triarylsilyl moiety in catalyst (J )-8b is crucial for high yield and the en-antioselectivity of the reaction in contrast with this the catalysts derived from AlMe3 and (J )-3,3 -disubstituted binaphthol (substituent = H, Me, Ph) were effective in stoichiometric amounts only and were less satisfactory with regard to reactivity and enantioselectivity. 

Few investigations have included chiral lanthanide complexes as catalysts for cycloaddition reactions of activated aldehydes [42]. The reaction of tert-butyl glyoxylate with Danishefsky s diene gave the expected cycloaddition product in up to 88% yield and 66% ee when a chiral yttrium bis-trifluoromethanesulfonylamide complex was used as the catalyst. 

In the reaction of benzylideneaniline with cyclopentadiene, the imine functions as an azadiene to yield the rearranged Diels-Alder adduct 77 (equation SI)44,453. In a study of the effect of various Lewis acids (ZnCl2, TiCU, Et2AlCl and SnCU) on diastereoselective cycloadditions of Danishefsky s diene to the imines 79, obtained from the chiral aldehydes 78 (R = MeO or Cl), it was found that SnCLj was the most effective, giving the optically active products in high yields and excellent ee values (equation 52)46. 

A particularly elegant example is the application of Danishefsky s diene [107] to the total synthesis of carbohydrates and carbohydrate derivatives. While it was known that activated aldehydes undergo cycloaddition with electron-rich dienes, the process was not efficient with typical aldehydes under thermal conditions. A major breakthrough was realized [108] with the development of the Lewis acid-catalyzed diene-aldehyde cyclocondensation (LACDAC) reaction, which provided a new strategy for the synthesis of carbohydrates and other polyoxygenated natural products (Scheme 1.4) [109],... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

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