Intramolecular Diels—Alder acrylates

The cross-conjugated trienes have potential in many different types of diversification strategies. For example, the triene clearly lends itself to inter- and intramolecular Diels-Alder reactions. Incorporation of the hydroxymethyl group on the tether allows attachment of functionality suitable for reactions subsequent to the Alder-ene reactions. As depicted in Scheme 8.5, propargyl tosylamides A, alkynyl silanes B, acrylate esters C, and propargyl ethers D can all be readily prepared from 39... 

It was suggested in the discussion of Section 2.07.5.1 that an intramolecular Diels-Alder reaction between a dihydropyridine and a-indolyl acrylate could be an efficient route to indole alkaloids. Although this has proven to be a successful reaction with A2-piperideines (Section 2.07.5.1), all attempts, most of which have not been reported in the literature, to apply this concept to dihydropyridines have been unsuccessful (81JOC3293). 

Diels-Alder reactions have been conducted on solid phase, with either the dieno-phile or the diene linked to the support [156]. The reaction conditions and the regio-and stereoselectivities observed are similar to those in solution [58,157,158]. Illustrative examples of Diels-Alder reactions leading to support-bound cyclohexenes are listed in Table 5.10. Further examples include the cycloaddition of polystyrene-bound 2-sulfonyl-l,3-butadiene and V-phenylmaIcimidc [51], the high-pressure cycloaddition of 1,3-butadienes to resin-bound 1 -nitroacrylates [95], and the intramolecular Diels-Alder reaction of styrenes with acrylates [159]. 

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

The non-selective thermal Diels-Alder reaction of hexa-2,4-dienol with methyl acrylate is made enantioselective by using the Lewis acid template (86) to assemble the reagents for cycloaddition.91 The Me2AlCl-catalysed intramolecular Diels-Alder... 

Good yields and purities were obtained for the two examples shown. Ugi reaction using solid-supported benzenesulfonamide, prepared by coupHng 4-carbox-ybenzenesulfonamide onto Rink resin, has also been described. The sulfonamide took the place of the amino component in the classical Ugi MCR. An extension of this Ugi reaction involving a support-bound amine, furfural, and an isonitrile and an acrylic acid was used by Schreiber [307] to generate support-bound dipeptides capable of performing intramolecular Diels-Alder reactions (see Section 4.5.9). 

Reaction of a 2,6-dimethylphenol (4) with lead tetraacetate in the presence of an excess of acrylic acid leads to ortho-qainol acrylates (5) which then can lead to tricyclic lactones (6) by intramolecular Diels-Alder cyclisation. ... 

A tandem Claisen/Diels-Alder sequence was recently used to construct the tricyclic structure found in a series of Garcinia natural products, represented by more-llin. On heating at 140 °C, acrylate ester 113 underwent an initial [3,3]-sigmatropic rearrangement to provide intermediate 114 (Scheme 20) (020L909). A subsequent intramolecular Diels-Alder cycloaddition then produced 115 in 92% yield. 

Some applications of Proton Sponge (1) for pericyclic reactions have been reported. Intramolecular Diels-Alder (IMDA) reaction of triene proceeded under thermal conditions to give bicyclic compound. In this reaction, the yield of the IMDA reaction for the Lewis acid labile substrate was significantly improved to 57% in the presence of a catalytic amount of Proton Sponge (1) (0.3 equiv.) [28] (Scheme 8.9). A similar effect was observed in the IMDA reaction of ester derivative. Whitney et al. conducted the IMDA reaction of acrylate... 

Two alternative intramolecular Diels-Alder reactions of the putative alkaloid precursor dehy-drosecondine (70) have been postulated as a branch point in the biosynthesis of aspidosperma and iboga alkaloids <62JA98>. Reaction by path a, in which the acrylate moiety acts as the dienophile generates the iboga skeleton, (69) while path b, with the vinylindole acting as a diene, gives the aspidosperma structure (71) (Scheme 147). 

Carbohydrate-derived Auxiliaries. - Reaction of the fructose-derived acrylate 200 with cyclopentadiene in the presence of Et2AlCl, followed by disconnection of the auxiliary by reduction, gave the cycloadduct 201 in high ee. Use of the same auxiliary in an intramolecular Diels-Alder reaction catalysed by Et2AlCl gave, after reductive disconnection with LiAlH4, the bicycle 2027 It has... 

If the asymmetric fragment exerting diastereomeric control were removable, and were itself optically pure, the result would be an enantioselective cyclization. Chiral acrylates have been used in the intermolecular Diels-Alder reaction, one of the more effective to date being phenylmenthyl (54). Roush has shown [56] that phenylmenthyl esters exert substantial diastereomeric control in the intramolecular Diels-Alder reaction also. 

Dauben has extended his studies on organic reactions at high pressure to include the Diels-Alder reaction of /7-benzoquinone with achiral and chiral dienoic esters enantiomeric excesses of up to 50% are achieved in the latter case. Unsaturated esters are produced by the EtAlQg-catalysed ene reaction of a-substituted acrylate esters and alkenes. The Lewis-acid-catalysed intramolecular Diels-Alder reaction of the trienecarboxylate ester (127) leads to (128)... 

The Diels-Alder reaction of ester-tethered trienes is also known as a powerful methodology to construct polycylic Y lactones [68]. Romo et al. [69] surveyed effective organic nucleophilic catalysts for tandem intermolecular Diels-Alder reaction/lactonization reaction of achiral a, 3-unsaturated acid chlorides with dienyl alcohol 100 (Scheme 45). In this case, when chiral Lewis base 102 was used as a nucleophilic catalyst, excellent enantioselectivity was realized. Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction of furfuryl alcohols with acrylic acids was also carried out by Akai and Kita [70]. 

Yateshas applied the intramolecular Diels-Alder reaction to the synthesis of the 2,<+a-ethano-2,3,4,Ua-tetrahydroxanthene system which is present in the naturally occurring compounds roorellin cind gambogic acid. The dienone 29 was generated by oxidation of the xanthene 2 , with lead tetraacetate in acrylic acid to give the desired system... 

The use of amides and imides as chiral auxiliaries in [4 + 2]-cycloadditions has been the subject of numerous investigations. Oppolzer reported the use of camphorsultam 112 in asymmetric Diels-Alder reactions [26, 67. 68], The camphor sultam is readily available in both enantiomeric forms from cam-phorsulfonyl chloride. Acrylate 113 was found to react with cyclopentadiene in the presence of EtAlCl2 to give 115 with high selectivity (endo/exo = 99.5 0.5, dr = 97.5 2.5, Equation 10) [67]. Oppolzer also reported that triene 116 participated in an intramolecular Diels-Alder cycloaddition reaction to afford endo product 117 in 71 % yield and 96.5 3.5 dr (Scheme 17.19) [69]. This bicyclic product was subsequently converted into the pyridine alkaloid (-)-pulo upone (118). 

Until recently, the reaction of a,p-unsatuiated esters with electron-rich alkenes has been reported to provide cyclobutane [2 + 2] cycloaddition products. Amice and Conia first proposed the intermediacy of [4 + 2] cycloadducts in the reaction of ketene acetals with methyl acrylate, and the first documented example of the 4ir participation of an a,3-unsaturated ester in a Diels-Alder reaction appears to be the report of Snider and coworkers in their description of the reversible, intramolecular [4 + 2] cycloaddition reaction of l-allylic-2,2-dimethyl ethylenetricarboxylates. Subsequent efforts have demonstrated that substitution of an a, -unsaturated ester with a C-3 electron-withdrawing substituent may permit their well-behaved 4ir participation in LUMOdiene-controlled Diels-Alder reactions (equation 3). ... 

Narasaka has demonstrated that TADDOL-Ti dichloride prepared from TADDOL and Cl2Ti(OPr )2 in the presence of MS 4A acts as an efficient catalyst in asymmetric catalytic Diels-Alder reactions with oxazolidinone derivatives of acrylates, a results in extremely high enantioselectivity (Sch. 45) [112]. Narasaka reported an intramolecular version of the Diels-Alder reaction, the product of which can be transformed into key intermediates for the syntheses of dihydrocompactin and dihydromevinolin (Sch. 46) [113]. Seebach and Chapuis/Jurczak [114] independently reported asymmetric Diels-Alder reactions promoted by chiral TADDOL- and 3,3 -diphenyl BINOL-derived titanium alkoxides. Other types of chiral diol ligands were also explored by Hermann [115] and Oh [116]. 

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