Enantioselectivity hetero-Diels-Alder reactions

Catalytic enantioselective hetero-Diels-Alder reactions are covered by the editors of the book. Chapter 4 is devoted to the development of hetero-Diels-Alder reactions of carbonyl compounds and activated carbonyl compounds catalyzed by many different chiral Lewis acids and Chapter 5 deals with the corresponding development of catalytic enantioselective aza-Diels-Alder reactions. Compared with carbo-Diels-Alder reactions, which have been known for more than a decade, the field of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds and imines (aza-Diels-Alder reactions) are very recent. 

Jorgensen K. A. Development and application of catalytic highly enantioselective hetero-Diels-Alder reactions of aldehydes and ketones in Curr. Trends Org. Synth.,... 

The scope of this methodology was extended to the enantioselective hetero-Diels-Alder reaction between 1,3-cyclohexadiene and ethylglyoxylate,... 

Finally, the discovery of exceptionally efficient catalysts for solvent-free enantioselective hetero-Diels-Alder reactions was made possible by a combinatorial approach.121 The object was to find a chiral titanium catalyst for the reaction of aldehydes (51) with Danishefsky s diene (91), with formation of cycloadduct (92) in >99% enantipurity (Equation (11)). 

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

TADDOL-Promoted Enantioselective Hetero-Diels-Alder Reaction of Danishefsky s Diene 37... 

An enantioselective hetero-Diels-Alder reaction between activated enones and 1,3-dioxin was reported. The Evans catalyst (r-Bu-box, Cu(OTf)2) was applied to obtain the bicycles in 65-81% yield and 91-96% ee (Equation 38) <2000JOC4487>. 

TABLE 9.19. ENANTIOSELECTIVE HETERO-DIELS-ALDER REACTIONS USING DANISHEFSKY S DIENE ... 

Figure 9.39. Natural products via enantioselective hetero-Diels-Alder reactions.

TABLE 9.20 ENANTIOSELECTIVE HETERO DIELS-ALDER REACTIONS OF a,P-UNSATU-RATED ACYL PHOSPHONATES, 560... 

The chiral bis(oxazoline)/Cu(II) complex with OTf or SbFg as a counter anion effectively promotes the enantioselective hetero Diels-Alder reaction of enol ethers with acyl phosphonates to give chiral enol phosphonates as synthetically useful chiral building blocks [64] (Eq. 8A.40). 

M. Johannsen, K. Jorgensen, X.-F. Zheng, Q.-S. Hu, and L. Pu, A highly enantioselective hetero-Diels-Alder reaction catalyzed by chiral polybinaphthyl-aluminum complexes, J. Org. Chem., 64 (1999) 299-301. 

The group of Yamamoto reported the catalytic enantioselective hetero-Diels-Alder reactions of azo compound 209 and dienes 208 (Scheme 2.54).87 In a ligand screening the use of BINAP (87) gave higher conversion and enantioselectivity than both Segphos (211) and Difluorphos (212). Interestingly, the optimal silver... 

The enantioselective hetero Diels-Alder reaction of 1-oxa-1,3-butadienes using chiral non-racemic Lewis acids is a widely unexplored field. The first successful example was the intramolecular cycloaddition of the heterodiene 2-194,... 

Lately, also an enantioselective hetero Diels-Alder reaction of a butadiene and glyoxylate in water has been described. The yields and the observed selectivities were higher in water, but the effect was not very pronounced [573],... 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

For the enantioselective hetero Diels-Alder reaction, very similar bis(oxazoline) complexes proved to be highly efficient [28]. The conversion of several unsaturated keto-esters 59 with ethyl-vinyl ether 60 gave cycloaddition products 61 in 97-99% ee. 

The chiral Ni(II) complex shown in Sch. 58 catalyzes the enantioselective hetero-Diels-Alder reactions of thiabutadienes with 3-(2-propenoyl)-2-oxazolidinone to afford optically active dihydrothiopyrans [204]. Similar results are obtained with analogous Cu(II) complexes where catalyst loading can be reduced when molecular sieves are added. 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

Saito, T, Takekawa, K, Takahashi, T, The first catalytic, highly enantioselective hetero-Diels-Alder reaction of thiabutadienes, Chem. Commun., 1001-1002, 1999. 

The first catalytic, highly enantioselective hetero-Diels-Alder reactions of thiabutadienes with an acyloxazolidinone dienophile using homochiral copper and nickel triflate and perchlorate bis(oxazoline) and bis(imine)complex catalysts to generate dihydrothiopyrans have been reported by Saito et al. [380],... 

Simonsen, K. B., Svenstrup, N., Roberson, M., Jorgensen, K. A. Development of an unusually highly enantioselective hetero-Diels - Alder reaction of benzaldehyde with activated dienes catalyzed by hyper-coordinating chiral aluminum complexes. Chem.- Eur. J. 2000, 6, 123-128. 

Bianchini, C., Giambastiani, G. Discovery of exceptionally efficient catalysts for solvent-free enantioselective hetero-Diels-Alder reaction. Chemtracts 2002,15, 672-676. 

Roberson, M., Jepsen, A. S., Jorgensen, K. A. On the mechanism of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral aluminum complexes-a concerted, step-wise or Mukaiyama-aldol pathway. Tetrahedron 2001, 57, 907-913. Monnat, F., Vogel, P., Rayon, V. M., Sordo, J. A. Ab Initio and Experimental Studies on the Hetero-Diels-Alder and Cheletropic Additions of Sulfur Dioxide to (E)-I-Methoxybutadiene A Mechanism Involving Three Molecules of S02. J. Org. Chem. 2002, 67, 1882-1889. 

The enantioselective hetero-Diels-Alder reactions of a,p-unsaturated acylphosphonates with enol ethers catalyzed by Cu(II)bzT(oxazoline) complexes have been investigated in depth. It was found that Cu(II)bA(oxazoline) complexes activate a,p-unsaturated acylphosphonates to the extent that they undergo facile cycloaddition reactions at low temperature with electron-rich alkenes. For example, dimethyl ( )-l-oxo-2-butenylphosphonate reacts with ethyl vinyl ether in the presence of Cu[(S,5)-t-Bu-box] (OTf)2 complex (10 mol% catalyst) to generate the cycloadduct in 89% yield (Scheme 7.86) with exceptional stereoselectivity (endo/exo = 99/1, 99% ee). Cyclic enol ethers also undergo stereoselective reactions with dimethyl ( )-l-oxo-2-butenylphosphonate. It specifically reacts with 2,3-dihydrofuran in the presence of Cu[(5,5)-t-Bu-box] (OTf)2 to deliver the bicyclic enolphosphonate. Of particular merit is the fact that a large variety of p.y-unsaturated acylphosphonates may be tolerated with no loss in selectivity for the derived cycloadducts. ... 

Evans, D.A., and Johnson, J.S., Catalytic enantioselective hetero Diels-Alder reactions of a,P-unsat-urated acyl phosphonates with enol ethers, J. Am. Chem. Soc., 120, 4895, 1998. 

New catalyst systems that display two hydrogen bond donating arms from a rigid oxazoline backbone of type 158 were prepared and applied to activate aldehydes in hydrogen bond promoted enantioselective hetero Diels-Alder reactions (ee up to 90%) <05OL5473>. 

Scheme 9.29 Enantioselective hetero-Diels-Alder reaction using a chiral niobium complex, reported by Kobayashi. ...

---