Acrylates intramolecular cycloadditions

Titanium ylides are generated from imine esters with titanium isopropoxide chlorides and amines or by transmetalation of the N-lithiated ylides (90,91). The regioselectivity of their reactions with methyl acrylate is opposite to that normally observed (90). A transition state is proposed in Scheme 11.13 to explain this alternative regioselectivity. Intramolecular cycloadditions of the titanium ylides offer a synthetic application of this regioselectivity. 

The intramolecular insertion of carbenoids into NH bonds is a potential route to aziridines. Scheme 81 shows an example of such a process <86JOC1120>. The starting material was prepared by the intramolecular cycloaddition of an azide with an acrylate followed by ring-opening of the resultant triazoline. 

Until recently, the reaction of a,/3-unsaturated esters with electron-rich olefins has been reported to afford 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,108 and the first documented example of the 4v participation of an a,/3-unsatu-rated ester in a Diels-Alder reaction appears to be the report of Snider and co-workers of the reversible, intramolecular cycloaddition of 1-allylic-2,2-dimethyl ethylenetricarboxylates.142 Subsequent efforts have recognized that substitution of the a,/3-unsaturated ester with a C-3 electron withdrawing substituent permits the 4w participation of such oxabutadiene systems in inverse electron demand Diels-Alder reactions with electron-rich olefins. In the instances studied, the rate of the [4 + 2] cycloaddition showed little dependence on solvent polarity [ aeetomtnie/ cycio-hexane — 3, Eq. (15) j acctomtnic toiuene 10, Eq. (20)], and reactions generally... 

Isotope effects for the Lewis acid-catalysed Diels-Alder reactions of isoprene with methyl vinyl ketone, ethyl acrylate, and acrolein support a highly asynchronous 4-1-2-cycloaddition. The intramolecular cycloaddition of )3-arylsulfonyl vinyl ketones with 1,1-disubstituted dienes produce either 4 - - 2- or 2 -I- 2-cycloadducts depending... 

Irradiation of the bisazirine (502) in the presence of methyl acrylate affords the phenanthro-imidazole (503) in a complex intramolecular cycloaddition reaction.The dibenzimidazole (505) is produced by the action of oxygen on the Schiff s base (504). ... 

The stracture of 13 is particularly suitable for an intramolecular cycloaddition since it eontains a 1,3-dipole (the nitronate fragment) and a dipolarophile (the acrylate fragment) linked by a two-methylene tether. The second step of the tandem reaetion is then clear. Once nitronate 13 is formed, an intramolecular [3+2] cycloaddition takes place to yield tricyclic nitroso acetal 9 (Scheme 22.9). 

Pyranopyrroloimidazoles have been prepared stereospecifically by an intramolecular 1,3-dipolar cycloaddition reaction. Either enantiomer of the imidazoline derivative 176 (the -enantiomer is shown) may react with the bromoacetyl-containing acrylate dipolarophile 177, in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to give the diastereomerically pure tricyclic product 178 in moderate yield (Equation 15). This reaction involves quaternization of the imidazole N, reaction of the quaternary salt with base to give the 1,3-dipole, which can then react, intramolecularly and stereospecifically, with the tethered dipolarophile <1997TL1647>. 

In this approach, the SENA skeleton is assembled from nitroalkene (42) and nucleophile 56.With the exception of two examples (entries 1 and 2 in Table 3.2), the reaction does not stop at SENA 51, which either undergoes intramolecular cyclization through [3 + 2]-cycloaddition to give fused heterocycles (as a rule after elimination of trimethylsilanol) (198-200) or is involved in [3+ 2]-cycloaddition with specially added methyl vinyl ketone or methyl acrylate to form (after elimination of silanol) substituted isoxazolines in rather high yields (201). 

Ogawa et al. (12) used an intramolecular azide-alkene cycloaddition strategy to synthesize the oxygen-bridged aza[15]annulene 52 and the aza[15]annulene dicar-boxylate 55 (Scheme 9.12). 1,3-Dipolar cycloaddition of vinyl azide to the acrylate moiety followed by extrusion of nitrogen gave the aziridine 51. Rearrangement of 51 afforded the aza[15]annulene 52. The same approach was used to synthesize the aza[15]annulene 55. 

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]. 

Most of the approaches outlined in Figure 15.10 have been successfully realized on insoluble supports, either with the alkene or alkyne linked to the support, or with support-bound 1,3-dipoles (Table 15.16). Nitrile oxides are highly reactive 1,3-dipoles and react smoothly with both electron-poor and electron-rich alkenes, including enol ethers [200]. The addition of resin-bound nitrile oxides to alkenes (Entries 5 and 6, Table 15.16) has also been accomplished enantioselectively under catalysis by diisopropyl tartrate and EtMgBr [201], The diastereoselectivity of the addition of nitrile oxides and nitrones to resin-bound chiral acrylates has been investigated [202], Intramolecular 1,3-dipolar cycloadditions of nitrile oxides and nitrones to alkenes have been used to prepare polycyclic isoxazolidines on solid phase (Entries 7 and 9, Table 15.16). 

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... 

In an approach to a dihydrooritidine analogue, the intermolecular [2 + 2]-photo-cycloaddition of 2, 3 -0-isopropylideneuridine to chiral and achiral acrylates was found to be unsatisfactory both with respect to regio- and diastereoselectivity. The intramolecular approach was more successful, and uridine 143 produced selectively the single diastereomerically pure product 144. Due to concurrent photodimerization and polymerization reactions, however, the yield was only moderate (Scheme 6.50) [136]. 

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