Allenylic carbonates

Electron-rich alkenes like an enol ether react with N-allenylsulfonamides to assist a 1,3-shift of the sulfonyl group, eventually furnishing formal [4+2]-cycloaddition products, tetrahydropyridine derivatives. The sulfonyl group migrates from the nitrogen to the central allenyl carbon atom [25b, 195]... 

Tsuji and co-workers carbonylated a-carbonate-substituted allenes 113 with carbon monoxide and methanol, which provided 114 in excellent yields (Scheme 14.25) [54], They found that allenylic carbonates are more reactive than simple allylic carbonates and that the reaction proceeded rapidly even at ambient temperature under atmospheric pressure of carbon monoxide. Unfortunately, the poor E/Z selectivity diminishes the synthetic value of this very efficient carbonylation reaction. 

Yu and co-workers have expanded upon Ojima s work through development of an effective Rh-catalyzed protocol for the cyclization/hydrosilylation of allenyl carbonyl compounds to form silylated vinylcycloalkanols and heterocyclic alcohols.For example, reaction of tosylamide 44 (X = NTs, R = H, n= ) and triethylsilane catalyzed by Rh(acac)(GO)2 (1 mol%) under GO (10 atm) at 70 °G for 8h gave the silylated vinyl pyrrolidinol 45 (X = NTs, R = H, n= ) in 74% yield with exclusive formation of the m-diastereomer (Equation (29)). The rhodium-catalyzed reaction was also effective for the cyclization of alleneones and for the formation of carbocycles, oxygen heterocycles, and six-membered cyclic alcohols (Equation (29)). However, Rh-catalyzed cyclization/hydrosilylation of allenyl carbonyl compounds that possessed substitution on an allenyl carbon atom was not established (Equation (29)). The efficiency of the Rh-catalyzed reaction of allenyl carbonyl compounds depended strongly on GO pressure. Reactions run under 10 atm GO were more efficient than were... 

Krause has shown that gold(III) salts catalyze the intramolecular emJo-hydroamina-tion of N-protected a-aminoallenes [35]. For example, treatment of the diasteromeri-cally pure a-allenyl sulfonamide 44 with a catalytic amount of AUCI3 in dichlor-omethane at 0 °C for 1 h formed the pyrroline derivative 45 in 95% yield with 96% diastereomeric purity (Scheme 11.6). The protocol tolerated aryl and alkyl substitution of the distal allenyl carbon atom and was also effective for the hydroamination of N-unprotected a-allenylamines although these latter transformations required considerably longer reaction time. In a similar manner, Lee has reported the gold (Ill)-catalyzed ewdo-hydroamination of 4-allenyl-2-azetidinone 46 to form bicydic P-lactams 47 (Eq. (11.25)) [36]. 

Widenhoefer and coworkers have reported that the gold(I) phosphine complex [P(t-Bu)2(o-biphenyl)]AuCl is a highly active and selective precatalyst for the intramolecular exo-hydroamination of N-y- and 8-allenyl carbamates [37]. As an example, treatment of the N-6-allenyl carbamate 48 with a catalytic 1 1 mixture of [P(t-Bu)20-biphenyl]AuCl and AgOTf (5mol%) in dioxane at room temperature for 22 h led to isolation of piperidine 49 in 92% yield as a 7.0 1 mixture of cis trans diasteromers (Eq. (11.26)). Gold(I)-catalyzed hydroamination of N-y- and 8-allenyl carbamates tolerated substitution at both the internal and terminal allenyl carbon atoms and the transformation displayed modest selectivity for the transfer of chirality... 

Krause has reported the gold-catalyzed intramolecular endo-hydroalkoxylation of (3-hydroxyallenes to form dihydropyrans [103]. For example, treatment of a 70 30 diastereomeric mixture of (3-hydroxyallene 61 with a catalytic 1 1 mixture of AuCl and pyridine in dichloromethane led to isolation of dihydropyran 62 in 84% yield as a 70 30 mixture of diastereomers (Eq. (12.32)). This transformation was also catalyzed effectively by a 1 1 mixture of (PPh3)AuCl and AgBp4 in toluene. (3-Hydroxyallenes that possessed substitution at the internal allenyl carbon atom also underwent gold-catalyzed cycloisomerization with selective transfer of chirality from the allenyl... 

In 2006, Widenhoefer reported an effective gold(I)-catalyzed protocol for the exo-hydroalkoxylation of y- and 6-hydroxy allenes to form 2-vinyl tetrahydrofurans and 2-vinyl tetrahydropyrans, respectively [104]. For example, treatment of 1-phenyl-5,6-heptadienol with a catalytic 1 1 mixture of [P(f-Bu)20-biphenyl]AuCl and AgOTs in toluene at room temperature led to isolation of 2-phenyl-6-vinyltetrahydropyran in 96% yield as a 7.2 1 mixture of diastereomers (Eq. (12.33)). This gold(I)-catalyzed hydroalkoxylation protocol tolerated substitution at the terminal allenyl carbon atoms and along the alkyl chain that tethered the hydroxy group to the allenyl moiety and was also effective for the S-exo hydroalkoxylation of y-hydroxy allenes. Alcaide and Almendros have shown that gold(III) also catalyzes the S-exo hydroalkoxylation of y-allenyl alcohols in modest yields (Eq. (12.34)) [105]. 

Shin has reported the gold(III)-catalyzed 5-endo cyclization of tert-butyl allenoates to form 2,4-disubstituted butenolides [116]. As an example, treatment of terf-butyl 2-benzyl-5-phenyl-2,3-pentadienoate with a catalytic amount of AUCI3 in dichloro-methane at room temperature for 1.5 h led to isolation of the butenolide 78 in 96% yield (Eq. (12.42)). The protocol tolerated a range of substitution at the allenyl carbon atoms. 

After nucleophilic attack on the central allenyl carbon, the resulting n-allyl intermediate is trapped by an intramolecular nucleophilic reaction, giving the initial 3-alkylidene-2,3-dihydrofuran product, and regenerating the palla-dium(O) catalyst. A mildly acidic work-up allows aromatisation, giving the final product. 

A solution of 0.10 mol of freshly distilled diethylaminopropyne in 80 ml of dry (distilled from phosphorus pentoxide) acetonitrile was cooled to 5°C and dry carbon dioxide was introduced into the vigorously agitated solution at a rate of about 0.3 1/min. The temperature rose above 20°C within a few minutes, but was kept at about 30°C by occasionally immersing the flask in a bath of ice-water. The introduction of CO2 was continued until the temperature had dropped to 25°C and the typical odour of the yneamine had disappeared completely. The yellow solution was concentrated in a water-pump vacuum. The residue, a sirupy liquid, had the theoretically required weight and consisted of reasonably pure (about 955 ) allenyl-diamide. If desired the product car be distilled (short-path distillation) in a high vacuum. It solidified upon standing at -25 C. 

The reaction of the o-iodophenol 275 with an alkylallene affords the bcnzo-furan derivative 276[184], Similarly, the reactions of the 6-hydroxyallenes 277 and 279 with iodobenzene afford the tetrahydrofurans 278 and 280. Under a CO atmosphere, CO insertion takes place before the insertion of the allenyl bond, and a benzoyl group, rather than a phenyl group, attacks the allene carbon to give 280. Reaction of iodobenzene with 4,5-hexadienoic acid (281) affords the furanone derivative 282[185]. 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

Terminal alkynes react with propargylic carbonates at room temperature to afford the alka-l, 2-dien-4-yne 14 (allenylalkyne) in good yield with catalysis by Pd(0) and Cul[5], The reaction can be explained by the transmetallation of the (7-allenylpailadium methoxide 4 with copper acetylides to form the allenyKalk-ynyl)palladium 13, which undergoes reductive elimination to form the allenyl alkyne 14. In addition to propargylic carbonates, propargylic chlorides and acetates (in the presence of ZnCb) also react with terminal alkynes to afford allenylalkynes[6], Allenylalkynes are prepared by the reaction of the alkynyl-oxiranes 15 with zinc acetylides[7]. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

The allenyl moiety (2,3-aikadienyl system) in the carbonylation products is a reactive system and further reactions such as intramolecular Diels-Alder and ene reactions are possible by introducing another double bond at suitable positions of the starting 2-alkynyl carbonates. For example, the propargylic carbonate 33 which has l,8(or 1.9)-diene-3-yne system undergoes tandem carbonylation and intramolecular Diels-Alder reaction to afford the polycyclic compound 34 under mild conditions (60 C, 1 atm). The use of dppp as ligand is important. One of the double bonds of the allenyl ester behaves as part of the dieneflSj. 

Allenyl Silyl enol ethers, 86 Allyl alcohol trimethylsilyl ether, 84 Allyl carbonates, 114-15 9 Allyl-ay 2 octalone, 34-5 2-Allyl-2 methylcyclohexanone, 106 (Allyldimethylsilyl)methyl chloride, 58, 59 (AUyldimethylsilyl)methylmagnesium chloride, 59... 

Very recently, Cook and Danishefsky [24] reported an interesting regioselectivity of intramolecular Diels-Alder reactions reversed by the change in the dienophihc moieties from vinyl to allenyl group (Scheme 19). For R = 2-propenyl group, C is bonded to the methyl substituted carbon Cj of the cyclohexadienone ring. For R = 2,3-butadienyl, C is bonded to Cy... 

The vinyl cation analog of an allylic carbonium ion is an allenyl cation 242, where the empty p orbital on the unsaturated carbon overlaps with the perpendicular n bond of the allenyl system. Allenyl cation 242 is of course a resonance form of the well known alkynylcarbonium ion,... 

Allenyl cations 1 are a stabilized form of vinyl cations1-3 in which the /1-carbon atom of the vinylic structure is part of the substituent which effects the stabilization of the ion via its electron-donating ability. This leads to a resonance hybrid having formally the alkynyl cation structure 2. Allenyl cations should be distinguished from the allenyl substituted carbenium ions 3 formulated as the mesomeric structures of the vinyl cations 4 (dienyl cations) stabilized by an w-vinyl group (equation 1). 

In general, allenyl cations 38 attack at the sp2-carbon atom of 1,3-dienes and form vinyl cations 39 and 40 (R = H, alkyl) or (R = aryl). Although a concerted cycloaddition mechanism is possible, a stepwise mechanism is preferred34. If a nucleophilic attack at the sp-carbon atom of the allenyl cation takes place, then cation 41 and the resulting cations 42 and 43 are formed. Some examples of bicyclic products obtained from cyclic 1,3-dienes and propargyl chlorides are given in equation 1534. 

The combination of a silyl-migration from carbon to oxygen and a prototropic isomerization leads to allenyl silyl ethers [246]. 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

The Pd-catalyzed reaction of propargyl electrophiles with carbon monoxide is a convenient route to allenyl carboxylic acid derivatives. In 1986, Tsuji et al. reported the Pd-catalyzed decarboxylation-carbonylation of propargyl carbonates under a CO at-... 

The palladium-catalyzed carbonylation of 4-amino-2-alkynyl carbonates 40 or 5-hydroxy-2-alkynyl carbonates 41 afforded a-vinylidene-/i-lactams 42 [60] or a-vinyl-idene-y-lactones 43 [61] in good yields (Scheme 3.25). The initially formed (allenyl-carbonyl)palladium(II) intermediates were trapped by the intramolecular amino- or hydroxy-nucleophiles to give 42 or 43. 

An analogous mechanism was proposed for the conversion of the triflate 416 to the vinyl-, allyl- and allenyl-A2-cephems 448 in yields of 47-71% by the respective tributyltin compounds in the presence of cuprous chloride (Scheme 6.91) [176]. Accordingly, the cyclic allene 417 should be liberated from 416 in the first step. Then, the organocopper species would transfer a hydrocarbon group to the central allene carbon atom of 417, leading to an allyl anion derivative, which is protonated during the workup. These reactions of 416 and 443 indicate that the cyclic allenes 417 and 444 behave toward nucleophiles as 1,2-cyclohexadiene (6) (Schemes 6.11— 13) and its non-polar derivatives such as 215 (Scheme 6.51), 221 (Scheme 6.52), 311 (Scheme 6.67) and 333 (Schemes 6.71 and 6.73), that is, they interact with nucleophiles at the central carbon atom of the allene system exclusively. 

Finally, the synthesis of allenyl ketones is also possible by carbonylation if carbonates 103 are treated with C-H acidic compounds 104 such as /3-diketones or derivatives of malonic ester to yield products of type 105 [143],... 

Another method to prepare allenyl ketones uses flash vacuum pyrolysis of the heterocycles 121 (Scheme 7.19) [163], This elimination of carbon monoxide is at least formally a cheletropic reaction. Highly reactive allenes such as esters and nitriles of type 124 or unsubstituted butadienal can be generated if retro-Diels-Alder reaction of 123 or similar precursors, respectively, is performed by flash vacuum pyrolysis [164]. 

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

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