Allyl carbonates cyclization

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

Nitrocycloalkanones can be successfully C-allylated by Pd(0)-catalyzed reaction with various allyl carbonates and 1,3-dienemonoepoxides under neutral conditions, as shown in Eqs. 5.56 and 5.57, respectively.801 The product of Eq. 5.56 is converted into cyclic nitrone via the reduction of nitro group with H2-Pd/C followed by hydrolysis and cyclization.80b... 

Similarly, 73-allylpalladium complexes were also employed as promoters for the cyclization.39,39a,39b The palla-dium(0)-catalyzed reaction of alkyne 168 with allylic carbonate in THF at 60 °G gave the A-allyl product 170 instead of the desired product 169. However, without isolation of 170, the reaction mixture was heated at 80 °G with 5 equiv. of K2CO3, providing 169 in 77% yield (Equation (7)). The nitrogen atom intervenes in the process as a nucleophile in the A-allylation step and as a leaving group in the cyclization step. 

The first example involving a rhodium catalyst in an ene reaction was reported by Schmitz in 1976. An intramolecular cyclization of a diene occurred to give a pyrrole when exposed to rhodium trichloride in isobutanol (Eq. 2) [15]. Subsequently to this work, Grigg utilized Wilkinson s catalyst to effect a similar cycloisomerization reaction (Eq. 3) [16]. Opplozer and Eurstner showed that a n -allyl-rhodium species could be formed from an allyl carbonate or acetate and intercepted intramolecularly by an alkene to afford 1,4-dienes (Eq. 4). Hydridotetrakis(triphenylphosphine)rhodium(l) proved to be the most efficient catalyst for this particular transformation. A direct comparison was made between this catalyst and palladium bis(dibenzylidene) acetone, in which it was determined that rhodium might offer an additional stereochemical perspective. In the latter case, this type of reaction is typically referred to as a metallo-ene reaction [17]. 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

Iodocyclization of trichloroacetimidates forms trans-1,3-oxazolines with moderate to good stereoselectivity (equation 118).234 Cyclizations of systems with internal double bonds (equation 119) generate 5-exo products only if the double bond has a (Z)-configuration (entries 2 and 3) or an oxygen substituent is attached to the allylic carbon (entries 3 and 4). Wc-153 ,i57b,254c... 

Inter-ring metal migrations, dynamic NMR studies, 1, 412 Intracyclic germanium-carbon bond formation large rings, 3, 706 small rings, 3, 703 Intramolecular Alder-ene reactions with metals, 10, 576 with palladium, 10, 568 with rhodium, 10, 575 with ruthenium, 10, 572 with transition metal catalysts, 10, 568 Intramolecular allylations, in cyclizations, with indium compounds, 9, 679... 

Ruthenium complexes are also suitable catalysts for carbonylation reactions of a variety of substrates. Indeed, when a reaction leads to C-Ru or het-eroatom-Ru bond formation in the presence of carbon monoxide, CO insertion can take place at the coordinatively unsaturated ruthenium center, leading to linear ketones or lactones. Thus, ruthenium-catalyzed carbonylative cyclization was involved in the synthesis of cyclopentenones by reaction of allylic carbonates with alkenes in the presence of carbon monoxide [124] (Eq. 93). 

Thermolysis of the racemic Y-sulfonimidoyl ketones 193 and 194 gave the 2,3-dihydrofurans 195 and 196, respectively.100 When a sample of 193 was being dried for combustion analysis at 50-60 °C, it was noticed that the sample rapidly turned black. H NMR analysis of the black solid indicated the formation of a novel product. When this thermal process was repeated on a preparative scale at 80-85 °C for 48 h, the novel 2,3-dihydrofuran 195 could then be isolated, as a single diastereoisomer, in 49% yield after purification by column chromatography. In addition, the known sulfonamide 197 and 4-methylbenzenesulfonamide 199 were also isolated in yields of 10 and 35%, respectively. The structure of compound 195 was unequivocally determined by a single-crystal X-ray structural analysis that showed that the allylic carbon (C(4)) in 193 had undergone inversion of stereochemistry on cyclization to 195. When a solution of 193 was heated to reflux in toluene for 2 h, the same three products 195,196, and 199 were isolated in yields of 42,18, and 32%, respectively. 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

Ruthenium-catalyzed carbonylations of allylic compounds [62] were described in Chapter 11. Here, ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes, not alkynes, which offers a new route to cyclopentenones is revealed [63]. Treatment of allyl methyl carbonate with 2-norbornene in the presence of 2.5 mol% [RuCl2(CO)3]2 and 10 mol% Et3N in THE at 120°C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltri-cyclo[5.2.1.0 ]dec-4-en-3-one, in 80% yield with high stereoselectivity exo 100%) (Eq. 5.37). 

In an imaginative construction of the angular triquinane ( )-hirsutene (158), Oppolzer and Robyr reported the carbonylative closure of allylic carbonate 155 to yield bicyclooctanes 156 and 157 (Scheme 6-27) [57]. In this multistep transformation, a alJylpalladium intermediate arising from the allylic carbonate 155 undergoes intramolecular Heck insertion of the pendant alkyne. Carbonylation of the resulting vinylpalladium intermediate, another Heck cyclization, and a second carbonylation then provide a mixture of acids, which after esterification yield esters 156 and 157 in good yield. 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

The Pd-catalyzed C-3 alkylation of indoles via nucleophilic allylic substitution on allylic carbonates and acetates has been described [90]. Two clever indole ring syntheses involving oxidative cyclization are illustrated below [91]. 

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

Pfaltz has examined intramolecular reactions and found that hgand, leaving group, and solvent all play a role in the regioselectivity of the cyclization and the C/O alkylation ratios. The best results were obtained with allyl carbonates in dichloromethane and the phosphinooxazoHne Hgand 29 where ees up to 87% are possible. The stereochemistry of the alkene does not affect the ee of the re-... 

Participation of nucleophiles in the cyclization of enynes gives rise to functionalized products. Thus, substrates containing an allylic carbonate unit are transformed into derivatives of 4-cycloalkene-l,2-diols. Without an internally participatory group an enyne can incorporate an amine. 

Intramolecular cyclizations of both the [2-3] and [3-2] patterns have been carried out with allylic carbonates. Thus both 63-A and 63-B gave good yields and enan-tioselectivity under the influence of Pd-catalysis [116]. 

Allylic alcohols are oxidized readily by silver carbonate. Cyclization and further oxidation then occur to give the lactone 9. See M. Fetizon, M. Golfler and J.-M. Louis,... 

VinyItetrahydrofurans were successfully synthesized via a palladium(0)-catalyzed cycloaddition of electron-deficient alkenes with allylic carbonates, as illustrated below 1J0C7142>. Another Pd(Il)-catalyzed cyclization of allylsilanes led to the formation of 2-vinyltetrahydrofurans <01CEJ4097>. 

Asymmetric cyclization of the cyclic allyl carbonate 241 is a good synthetic method for 9-azabicyclo[4.2.1]non-2-ene system 242, which can be converted to... 

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