Esters allenic, cycloaddition

Reaction of the nitrone 4-184 with allenic esters 4-185 as described by Ishar and coworkers led to the benzo[b]indolizines 4-186, together with small quantities of 4-187 (<5%) (Scheme 4.40) [63]. The first transformation is a 1,3-dipolar cycloaddition this is followed by four further steps, including a [4+2] cycloaddition of an intermediate 1-aza-l,3-butadiene. 

Some cases are known in which Diels-Alder reactions of electron-deficient allenes and dienes compete with [2 + 2]-cycloadditions (see also Section 7.3.7) [12, 151, 335, 336]. Recently, a phosphane-catalyzed [4 + 2]-annulation starting from allenic ester 337 and N-tosylaldimines 338 was published [337]. However, the formation of the tetrahydropyridines 339 isolated in excellent yields is explained by a multi-step mechanism and only resembles a Diels-Alder reaction. 

Allenic esters such as 349 [12] or allenyl ketones such as 351 [42] are able to undergo intramolecular [4+2]-cycloadditions with participation of both the inactivated or the activated C=C bond of the allene, respectively. The latter starting material is consumed at room temperature, yielding only one product. However, similar... 

The Lewis acid-promoted [4+ 2]-cycloaddition reaction of the allenic ester 103 having a camphor-derived chiral auxiliary with cydopentadiene provided the adduct with excellent Jt-facial selection, leading to an enantioselective synthesis of (-)-/l-san-talene [92]. 

Both uncatalyzed and catalyzed [4+2]-cycloaddition reactions of furans with the allenic esters have been reported (Table 12.6) [93]. The allene adds from the less hindered C1-C2 Jt-face. The unfavorable steric interaction between the a-hydrogen atom of the furan and the methyl group at C4 of the allene is responsible for this selectivity. The more reactive 2-methylfuran adds to the allenic ester also in a regio-selective manner. The C2 carbon atom of 2-methylfuran was exclusively attached to the Cl carbon atom of the allenic ester, providing a mixture of endo- and exoadducts. 

Table 12.6 Uncatalyzed and catalyzed cycloaddition reactions of furans with allenic esters...

Allenic ketones undergo a thermal cycloaddition reaction with 1,3-dienes. The carbon-carbon double bond proximal to the carbonyl group reacts exclusively as in the case of allenic esters [105]. 

Intramolecular Cycloaddition of Activated Allenes 12.4.2.1 Allenic Esters... 

The methylenepyrazoline 69, formed from cycloaddition between an allenic ester and DAP, rearranges to 70 on slow distillation over glass wool (Scheme 25).115... 

In a [4+2] cycloaddition reaction that proceeds via a Michael addition, an azadiene has been shown to react with Fischer carbenes yielding the 1,4-dihydropyridine after removal of the metal (Scheme 82) <1997TL3981>. Reactions of 1-azadienes with allenic esters yield the 1,4-dihydropyridine in excellent yield (Scheme 83) <20010L2133>. 

Although obtained only in low yields upon troublesome chromatography of product mixtures that contained much polymeric material, the tricyclic benzofuran and benzothiophene lactones (61) were shown to be isolable products from attempted Diels-Alder reactions on the allene ester precursors shown in Equation (32) <85JCS(Pl)747>. Although it was noted in the case of the two thiophenes that the tricyclics appeared to be forming from a precursor (presumably a dihydro form) on the chromatographic column, it was not possible to convert the crude suspected cycloaddition adducts directly into the aromatics by dehydrogenation with DDQ. Complex mixtures were obtained instead. It is possible that the actual dienophiles in these Diels-Alder reactions are alkynes. In a related study, the bis-lactone (62) was also obtained (Equation (33)) <86H(24)88l>. 

Kiefer and Okamura 73> demonstrated stereoselectivity with respect to the olefinic component in an allene-olefin cycloaddition. 1,1-Dimethyl-allene with dimethyl fumarate at 160—180 °C gave two cycloadducts, both retaining the trans disposition of ester functions with better than 99% stereoselectivity dimethyl maleate gave the isomeric cis adducts with... 

The allenic ester 4 of (R)-l also undergoes a highly diastereoselective cycloaddition with cyclopentadiene to afford the e do-adduct 5 almost exclusively and in 99% de. The adduct provides a chiral intermediate to natural (- i-P-santalene (6).-... 

The photoaddition of allenic esters (31) to the enone (32) has been studied. The major products from these reactions are the dienes (33) and the cyclobutanes (34) and (35). It seems likely that the addition proceeds by the traditional biradical path to an intermediate such as (36). Dis-proportionation affords (33) while C-C bond formation yields the two cyclobutanes.The cycloaddition of isobutylene to the enone (37a) in a variety of solvents affords the adduct (38, 20-40X) and the alkylated... 

More recently, allenes, acetylenes and activated dienes have been added as olefin equivalents, leading to products of more eomplex skeletons. Though the first report on allenic compounds involved in a MBH reaction dates back to the DABCO-catalyzed and butyllithium-promoted aldol condensation of allenic ester with aldehydes reported by Tsuboi et there are very few reports of MBH reactions involving allenoates because they easily undergo cycloaddition reactions under different Lewis bases. For instance, five-membered pyrrolidine... 

The [3+2] cycloaddition reactions of fluoro- and 1,1-difluoroallenes with diazoalkanes also afford the cycloadducts resulting from addition across the non-substituted double bonds in high yields Likewise, allenic esters undergo cycloaddition reactions with diazoalkanes, mainly across the double bond containing the ester substituent. ... 

Allenic esters have also been shown to add to fiirans in a highly regio- and stereo-specific fashion [25]. Lewis acids such as Eu(fod)3 and Pr(fod)3 were found to catalyze these cycloadditions. Several mol% significandy enhanced the selectivities and yields of these reactions without adversely affecting fragile functionalities. Particularly reactive bis-ester allenes such as 1,3-dicarboethoxyallene underwent rapid smooth cycloaddition with furan and 2,5-dimethylfuran at... 

Singh et al. (2008) studied a microwave-assisted [4+2] cycloaddition reaction for the synthesis of unsymmetrically substituted 1,4-dihydropyridines. 1,4-Dihy-dropyridine analogs such as Nifedipine and Nimodipine are well known for their potent biological activities. Microwave-assisted [4+2] cycloaddition of 1,4-diaryl-1-aza-1,3-butadienes with allenic esters at 100°C for 5-17 min gave cycloadducts in excellent yields (83-96%), which after a tandem 1,3-H-shift furnished unsymmetrically substituted 1,4-dihydropyridines. 

Catalysis of [2 + 2] Cycloadditions. EtAICI2 catalyzes a wide variety of [2 + 2] cycloadditions. These include the addition of alkynes or allenes to alkenes to give cyclobutenes and alkyli-denecyclobutanes (eq 14), the addition of electron-deficient alkenes to allenyl sulfides (eq 15), the addition of propiolate esters to monosubstituted and 1,2-disubstituted alkenes to form cyclobutene carboxylates (eq 16), and the addition of allenic esters to alkenes to form cyclobutanes. ... 

A novel asymmetric [4-1-2] cycloaddition of, y-unsaturated a-keto-phosphonates (347) with allenic esters (348), afforded the corresponding phosphonate-substituted functionalised pyran (349a) or dihydropyran (349b) derivatives in good yields and enantioselectivities which were important structural subunits in many natural products, drugs and biologically active molecules (Scheme 118). ... 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Thus far, the [5 + 2 + 1]-reaction works efficiently with alkynyl esters, amides, aldehydes, and ketones or an alkynyl-substituted allene44 as the two-carbon component (Scheme 58). Just as in the case of the [5 + 21-cycloaddition of VCPs and allenynes, the [5 + 2 + l]-reaction is selective for the allene over the alkyne subunit (Equation (35)). 

As exemplified in Eq. 8.38, thermal [2 + 2] cycloadditions of 4-vinylidene-2-oxazoli-dinone 287 and alkynes such as phenylacetylene result in the formation of 3-phenyl-substituted methylenecyclobutene 288 [149]. The authors confirmed by NMR analysis that only the Z-configuration isomer was formed. It is worth noting that the [2 + 2] cycloaddition of allenes 287 is not restricted to alkynes even olefins such as acrylic esters or silyl enol ethers furnish the corresponding methylenecyclobutanes... 

Intramolecular [4 + 2]-cycloaddition reactions of allenic acids and esters proceeded in refluxing toluene to give bicyclic compounds with the exo-isomer predominating (Table 12.9) [120]. When a Lewis acid was used as a promoter, the [4 + 2]-cydoaddi-tion occurred at 0 °C and the endo-isomer was favored. 

Table 12.9 Cycloaddition reactions of allenic acids and esters.

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