Hetero Diels-Alder reaction cationic

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

Evans has reported that the cationic C2-symmetric chiral Lewis acid Cu(ll)bis(oxazoline) complex promotes the hetero-Diels-Alder reaction of 0 ,/3-unsaturated acyl phosphonates with enol ethers to give the cycloadducts with excellent ee (Scheme 52). As well as simple dihydropyrans, various fused bis-dihydropyrans are also reported <1998JA4895, 2000JA1635>. 

S. Oi, E. Terada, K. Ohuchi, T. Kato, Y. Tachibana, and Y. Inoue, Asymmetric hetero Diels-Alder reaction catalyzed by chiral cationic palladium(II) and platinum(II) complexes, J. Org. Chem., 64 (1999) 8660-8667. 

The advantagous use of Lewis acids in the hetero Diels-Alder reaction of carbonyl compounds has intensively been studied and employed by Danishefsky et al. [23,67-70], They also showed that rare earth cations are excellent and mild catalysts due to their high oxophilicity, even allowing the isolation of the highly sensitive primary cycloadducts. 

Good results were also obtained with lithium perchlorate in dichloromethane and diethyl ether. It has been shown that the lithium cation acts as a Lewis acid and the effects are not due to an internal pressure [80]. The acceleration is much more pronounced for hetero Diels-Alder reactions as compared to the allcarbon cycloadditions. With chiral aldehydes a high level of chelation control has been observed (see later) [81,82]. 

Blechert et al. have opened a very elegant alternative to the classical hetero Diels-Alder methodology by generating the cationic radical 3-31 - which might be conceived as 1-aza-1,3-butadiene - from the 2-vinyl indole 3-30 by means of a single electron transfer process. In the presence of the tetrahydropyridine derivative 3-32 the radicalic intermediate was transformed into the tetracyclic compound 3-33 which contains the complete skeleton of the alkaloid gonio-mitine [250, 251]. The authors have postulated a stepwise mechanism for this [4+2] process, therefore it should be understood as a formal hetero Diels-Alder reaction (Fig. 3-11). 

Diels-Alder type [4 -1- 2] cycloadditions of nonactivated coupling partners have been effected by various transition-metal catalyses [1]. Interestingly, the cationic ruthenium complex 68 catalyzed the intramolecular [4 -1- 2] cycloaddition between alkyne and enone moieties of 97 leading to 98 (Scheme 4.38) [83]. Such a formal hetero Diels-Alder reaction might proceed via a mthenacyclopentene 99 and an oxam-thenacycloheptadiene 100, which is an mthenium enolate species. 

Continuous effort by Righetti et al. was devoted to investigation of the effect of different metal salts on the rate of the Diels-Alder and hetero-Diels-Alder reaction in acetone solution (Sch. 3) [22]. LiClOq, NaC104, Ba(C104)2, and Mg(C104)2 were compared to evaluate the distinctive Lewis acidic nature of each species. When the effect of different cations is compared at the same concentration, Na is 2-3 times less effective than Li, which is 2-3 times less effective than Ba. The outstanding result, however, is that Mg is ca... 

L-Iduronyl synthons catalyzed by a vinyl cerium reagent have been shown to open a way to an efficient preparation of l,2,4-tri-0-acetyl-3-0-benzyl-Z,-iduronyl derivatives.1097 The synthetic utility of the cationic lanthanide complex [Cp 2Ce][BPh4] as an effective Lewis acid catalyst for the hetero-Diels-Alder reaction between Danishefsky s diene and substituted benzaldehydes has been demonstrated (Scheme 307). 

Though thioketones have been used as dienophiles in hetero Diels-Alder reactions (20), only one example has been reported for the use of a thienium cation as a dienophile (21). 

Hetero-Diels-Alder reaction. High enantioselectivity is observed for this process using chiral cationic Pd(II) complexes. ... 

These unusual results raise the question how LiC104 influences the course of these and further reactions. The similarity to the accelerating effect of water as solvent for carbo- and hetero Diels-Alder reactions suggests that an internal pressure might be operative, [5,13] but also an electrostatic catalysis by ion pairs [14] might be involved if polar transition states are passed. Finally, the lithium cation may serve as Lewis acid in an essentially non-acidic medium, a notion... 

Hetero Diels-Alder reactions A related cationic complex Pd(dppp)(PhCN)2 BF ), is able to promote the condensation of dienes with aldehydes to form dihydropyrans. 

Among the Lewis acids studied in asymmetric hetero Diels-Alder reactions of carbonyl compounds rare earth cations proved to be mild and efficient catalysts. This is demonstrated by the results observed in reactions of camphor sultam (63) derivatives with achiral 1-methoxy-l,3-butadiene. 

Aungst and Funk reported studies on the related a-siloxy- 3-substituted acroleins such as 84 almost contemporaneously (Scheme 18.17) [23]. Siloxyacrolein 84 was prepared by a retro-hetero-Diels-Alder reaction of dioxin derivative 83. Compared with 79, compound 84 bears an additional carbon substituent that would further stabilize siloxyallyl cation 85 and favored its formation, with the result that even acyclic dienes like butadiene underwent [4+3] cycloaddition effectively. 

Chiral cationic coppei(Il)-bis(oxazoline) complexes such as 162 are effective in promoting enantioselective hetero-Diels-Alder reactions with a broad variety of substrates [124]. Evans has reported that complex 162 catalyzes the inverse-electron-demand hetero-Diels-Alder reaction between enol ether 245 and enone 246 to give dihydropyran 247 in 97 % ee and 94 6 dr (Scheme 17.35) [125]. After diastereoselective reduction of the tetrasubsti-tuted olefin in 247, tetrahydropyran 248 was isolated in 95 % yield and dr= 98 2. This tetrahydropyran served as a common intermediate to access the 1,3-syn dimethyl motifs embedded in both the E- and the Hl-ring fragments 249 and 250, which served as key intermediates in an efficient synthesis of the marine shellfish toxin azaspiracid-1 (251). 

Stereoselective Diels-Alder reactions have been reported in several cases. Enantioselective Diels-Alder reactions of l-phenoxycarbonyl-l,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using a chiral cationic palla-dium-phophinooxazolidine catalyst afforded chiral isoquinuclidines with excellent enantioselectivity <2005TL5677>. Bismuth(lll) chloride-mediated diasteroselective intramolecular [4-f2] cycloaddition reactions of A-allyl derivatives of pyrazole aldehydes led to fused sulfur-containing pyrazole heterocycles <2003SC3063>. A highly diastereoselective intramolecular hetero-Diels-Alder approach toward tetracyclic pyrazoles from 5-(3-methyl-2-butenylthio)-3-methyl-l-phenyl-4-pyrazolecarboxaldehyde has been reported <1997SL1155>. 

Various types of electron-deficient sulfur diimides react as hetero-dienophiles. In general, these cycloadditions occur under conditions similar to those used for AT-sulfinyl compounds. However, fewer types of sulfur diimides have been utilized in this process relative to Af-sulfinyl compounds. Some examples of symmetrical sulfur diimide Diels-Alder reactions are listed in Table l-II. It should again be noted that the orientational selectivity in these cycloadditions is the same as that shown by N-sulfinyl systems (cf. Table l-I). Several examples of cycloadditions with unsymmetrical sulfur diimides are shown in Table l-III. In all cases, these reactions were totally regioselective, and as noted above, reactions occurred at the least electron-deficient nitrogen-sulfur bond. Frontier molecular orbital (FMO) theory has been used to rationalize the regio-selectivity of addition of the cationic sulfur diimide shown in entry... 

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