Asymmetric reactions Diels-Alder cycloaddition

The polymer-supported Zr catalyst (12) is useful for asymmetric aza-Diels-Alder cycloaddition of benzaldehyde imine to Danishefsky diene [9]. The 6-substituted BINOL-Zr(IV) catalyst is useful for the enantioselective anft -preferred aldol reaction of benzaldehyde with ketene silyl thioacetal (15) (Scheme 5.5) [ 10]. The calculated charge densities on the oxygen atoms of the BINOL derivatives revealed that there is a good correlation between the charge density and the reactivity of 6-substituted BINOL [ 10]. 

Guingant has shown that asymmetric hetero Diels-Alder cycloadditions could be carried out under high pressure [63]. He used an as5unmetric route to the 5,6-dihydro-4H-l,3-thiazine skeleton via an asymmetric hetero Diels-Alder reaction (Scheme 42). Without catalyst, product 174 is formed preferentially, while the addition of Lewis acid catalyst reverts to enantioselective formation of product 173. When cycloaddition is performed at atmospheric pressure (dichlo-romethane, 110 °C, 20h, 75%), ratio of products is almost identical to high-pressure reaction (20 80), and with the addition of MgCl2 catalyst (at 0°C, 3h) the ratio 173 174 of 100 0 shows the same enantioselectivity as high-pressure conditions. 

Asymmetric induction in the intermolecular Diels-Alder cycloaddition reactions can be achieved with chirally modified dienes and dienophiles as well as with chiral Lewis-acid catalysts [54-56]. 

Bis(oxazoline)-type complexes, which have been found useful for asymmetric aldol reactions, Diels-Alder, and hetero Diels-Alder reactions can also be used for inducing 1,3-dipolar reactions. Chiral nickel complex 180, which can be prepared by reacting equimolar amounts of Ni(C10)4 6H20 and the corresponding (J ,J )-4,6-dibenzofurandiyl-2,2 -bis(4-phenyloxazoline) (DBFOX/Ph) in dichloromethane, can be used for highly endo-selective and enantioselective asymmetric nitrone cycloaddition. The presence of 4 A molecular sieves is essential to attain high selectivities.88 In the absence of molecular sieves, both the diastereoselectivity and enantioselectivity will be lower. Representative results are shown in Scheme 5-55. 

The asymmetric Diels-Alder cycloadditions of enantiopure (5)-5-(/ -tolylsulfinyl)-1,4-benzoquinones with Dane s diene under thermal and Lewis acid conditions produce tetracyclic quinones after spontaneous elimination of the sulfinyl group.The Diels-Alder reaction of barrelene with o-benzoquinone produces tetracyclo[6.2.2.2 .0 ]tetradeca-9,ll,13-triene-4,5-dione. Under kinetic control, the Diels-Alder cycloaddition of 2,3-dicyano-p-benzoquinone (98) with cyclopentadiene in MeOH produces the single cycloadduct (99) (Scheme 38). ... 

An interesting expansion to the scope of dienes that could be adopted as partners within the Diels-Alder cycloaddition was reported by Deng (Scheme 57) [193]. Reaction of 3-hydroxypyrones 145 with a broad range of a,p-unsaturated ketones in the presence of the primary cinchona alkaloid 144 (5 mol%) provided the Diels-Alder adducts with exceptional levels of asymmetric induction (up to 99% ee). Within this report it was also shown that the related alkaloid 146 provided access to the enantiomeric adducts with similar levels of asymmetric induction. 

Then the potential for asymmetric induction of some of these chiral ionic liquids was investigated. The aza Diels-Alder cycloaddition between the enantiomericaUy pure (/ )-imine 31 and the Danishefsky s diene 32 was chosen as model asymmetric reaction (Scheme 8). The reaction was performed at room temperature for 5 h using 0.5 equiv. of ionic liquid and 1.5 equiv. of diene. In the absence of chiral ILs, the same coupling required a Lewis acid catalyst (0.1 equiv. of ZnC ) and afforded the main product 33 in 60% yield and low diastereoselectivity (32% de). 

Yamamoto reported an aluminum complex-catalyzed asymmetric hetero Diels-Alder reaction (Scheme 9.19) [36]. Chiral ketone d-3-bromocamphor discriminates (R)-organoaluminum complex 34 from (S)-complex 34 by diastereoselective complexation, whereas the remaining (S)-isomer 34 catalyzes the enantioselective cycloaddition of an activated diene to benzaldehyde. 

The intermolecular Diels-Alder reaction between the dibromoenone (111) and dienes (112) provides access to bicyclo[5.4.0]undecane systems (113) that are common core structures of many natural products (Scheme 32).118 The alio-threonine-derived O-(/ -biphenyl carbonyl oxy)-/i-phenyloxazaborolidi none catalyses the enan-tioselective Diels-Alder reaction of acyclic enones with dienes.119 The reversal of facial selectivity in the Diels-Alder cycloaddition of a semicyclic diene with a bro-moenone was induced by the presence of the bromo substituent in the dienophile.120 Mixed Lewis acid catalyst (AlBr3/AIMe3) catalyses the Diels-Alder reaction of hindered silyloxydienes with substituted enones to produce highly substituted cyclohexenes.121 Chiral /V-enoyl sultams have been used as chiral auxiliaries in the asymmetric Diels-Alder reactions with cyclopentadiene.122... 

The use of Lewis acids in order to catalyze hetero Diels-Alder reactions of thia-1,3-butadienes is not widespread, but recent investigations stemming from Saito et al. reveal a remarkable acceleration of these transformations in the presence of A1C13 or EtAlCl2 [428]. In a first study concerning asymmetric hetero Diels-Alder reactions of thia-1,3-butadienes, Saito et al. found Lewis acids to have a beneficial effect on the induced diastereoselectivities. Thus, the thioketone 5-17, generated in situ by thermal cycloreversion from its dimer, underwent a completely endo-selective cycloaddition upon treatment with (-)-dimenthyl... 

N-Acylimines which may react as l-oxa-3-aza-l,3-butadienes represent a class of heterodienes which exhibit a close relationship to l-thia-3-aza-l,3-butadienes [13]. A very impressive application of such an l-oxa-3-aza-l,3-butadiene has been worked out by Swindell et al.[445]. The asymmetric hetero Diels-Alder reaction described therein opens a very elegant approach to the A-ring side chain of taxol. This synthesis takes advantage of the bulky chiral auxiliary attached to the dienophile 6-5 which upon cycloaddition with the l-oxa-3-aza-1,3-butadiene 6-4 yielded the 1,3-oxazine derivative 6-6. Subsequent hydrolysis, hydrogenolysis and transesterification gave the methyl ester of the taxol A-ring side chain 6-7 in good endo and excellent zr-facial selectivity (Fig. 6-2). 

Evans DA, Chapman KT, Bisaha J (1984) New asymmetric Diels-Alder cycloaddition reactions. Chiral a,fS-unsaturated carboximides as practical chiral acrylate and crotonate dienophile synthons. J Am Chem Soc 106 4261-4263... 

Diels-Alder Cycloaddition Reactions. Catalysts 1 and 2 facilitate asymmetric Diels-Alder cycloaddition reactions between propenyl oxazolidinones (and thio-oxazolidinones) and dienes such as cyclopentadiene (eq 2). Both 1 and 2 display sim-... 

Hetero-Diels-Alder Cycloaddition Reactions. Copper-bis-(oxazoline) complex (2) facilitates a variety of asymmetric hetero-Diels-Alder reactions between a diverse range of substrates. A... 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

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