Enantioselective reactions hetero-Diels-Alder reaction

Thorhauge, J, Johannsen, M, Jprgensen, K A, Highly enantioselective catalytic hetero-Diels-Alder reaction with inverse electron demand, Angew. Chem. Int. Ed., 37, 2404-2406, 1998. 

Table 5.3 Enantioselective catalytic hetero Diels-Alder reaction of 13...

Diastereoselectivity and enantioselectivity of hetero Diels-Alder reactions can be increased by applying high pressure. For instance, Tietze [67] showed that for hetero Diels-Alder reaction of the enamino ketone 182 and ethyl vinyl ether 183, a significant increase of diastereoselectivity can be obtained by applying the high pressme (Scheme 44). 

Recently, Jacobsen described a novel strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly active intermediate through a network of non-covalent interactions (as shown in transition state Q) [69]. Accordingly, a highly efficient and enantioselective aza-hetero-Diels-Alder reaction between N-aryl imines 152 and enamide 153 or ene-carbamate 154 has been achieved with the use of the combination of the bifunctional sulfinamido urea derivative 155 and ortho-nitrobenzensulfonic acid (156) (Scheme 38.46). The 2 1 ratio of 155 and 156 was essential to ensure the complete suppression of the racemic pathway catalyzed by 156 [69]. 

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 enantioselectivity obtained in the hetero-Diels-Alder reaction (Scheme 12) was low (18% ee). This is, in part, due to the important temperature effect. For example, 50% ee was obtained in reactions carried out in homogeneous phase at - 60 °C and 95% ee in reactions at - 78 °C. However, at 0 °C the enantioselectivity dropped to 28% ee, a value closer to that obtained with the immobilized catalyst at the same temperature. Recycling was investigated and the solid was used four times with the same activity maintained. The 6b-Cu(OTf)2 catalyst proved to be less effective for this reaction and less stable in terms of recycling, a situation in agreement with the results obtained with exchanged catalysts [53]. 

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

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

Optically active /3-ketoiminato cobalt(III) compounds based on chiral substituted ethylenedi-amine find use as efficient catalysts for the enatioselective hetero Diels Alder reaction of both aryl and alkyl aldehydes with l-methoxy-(3-(t-butyldimethylsilyl)oxy)-1,3-butadiene.1381 Cobalt(II) compounds of the same class of ligands promote enantioselective borohydride reduction of ketones, imines, and a,/3-unsaturated carboxylates.1382... 

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)). 

Jorgensen s group44a carried out the reaction using the anhydrous form of chiral bis(oxazoline) coordinated copper complex. Complex 106 containing 83 as the chiral ligand was found to be the most effective. As shown in Scheme 5-32, the asymmetric hetero Diels-Alder reaction of //.y-unsaturated a-keto esters with acyclic enol ethers results in products with excellent yield and enantioselectivity. 

A similar enantiomer-selective activation has been observed for aldol " and hetero-Diels-Alder reactions.Asymmetric activation of (R)-9 by (/f)-BINOL is also effective in giving higher enantioselectivity (97% ee) than those by the parent (R)-9 (91% ee) in the aldol reaction of silyl enol ethers (Scheme 8.12a). Asymmetric activation of R)-9 by (/f)-BINOL is the key to provide higher enantioselectivity (84% ee) than those obtained by (R)-9 (5% ee) in the hetero-Diels-Alder reaction with Danishefsky s diene (Scheme 8.12b). Activation with (/ )-6-Br-BINOL gives lower yield (25%) and enantioselectivity (43% ee) than the one using (/f)-BINOL (50%, 84% ee). One can see that not only steric but also electronic factors are important in a chiral activator. 

The asymmetric hetero-Diels-Alder reaction of aldehydes with Danishefsky s diene catalyzed by Ti catalysts generated from a library of 13 chiral ligands or activators has also been reported (Scheme 8.18). The catalyst library contains 104 members. The Ti catalysts bearing L, L , L, and J are found to have a remarkable effect on both enantioselectivity (76.7-95.7% ee) and yield (63-100%). On the other hand, ligands bearing sterically demanding substituents at the 3,3 -positions are found to be detrimental to the reaction. The optimized catalysts, both L /Ti/L and L /Ti/L , are the most efficient for the reaction of a variety of aldehydes, including aromatic, olefinic, and aliphatic derivatives. 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

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

The enantioselechve hetero-Diels-Alder reaction of carbonyl compounds with 1,3-dienes represents an elegant access to optically active six-membered oxo-heterocy-cles. Since the pioneering work of Rawal et al. in 2003 [40], the enantioselective HDA reaction catalyzed by diols (such as TADDOLs) has become a flourishing field of research [41]. 

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>. 

The development and application of catalytic enantioselective 1,3-dipolar cycloadditions is a relatively new area. Compared to the broad application of asymmetric catalysis in carbo- and hetero-Diels-Alder reactions (337,338), which has evolved since the mid-1980s, the use of enantioselective metal catalysts in asymmetric 1,3-dipolar cycloadditions remained almost unexplored until 1993 (5). In particular, the asymmetric metal-catalyzed reactions of nitrones with alkenes has received considerable attention during the past 5 years. 

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... 

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