Carboxylation of allenes

This stoichiometric chemistry has been revisited in the last few years [60,79-82] and, for instance, applied to the s)mthesis of a-methylene-y-hydroxy carboxylic acids and their derivatives (c/s-p.y-disubstituted a-methylene-y-lactones) by means of nickel-mediated sequential addition of carbon dioxide and aldehydes into terminal or internal allenes [80, 81], or exploited for the preparation of P-hydroxycarboxylic acid derivatives by 02-oxidation of the Ni-n -allyl species (5.8) 

Unsaturated carboxylic acid magnesium salts have been obtained catalytically by reductive electrocarboxylation of a number of allenes with a L Ni(II)-complex [L = bpy, dppe, PMDTA (A,A,A W A -pentamethyldiethylene triamine)], as the catalyst, in the presence of a sacrificial magnesium anode [46, 83] (see also Sect. 5.3).However, regioselectivity was moderate. In additimi to a,p-unsaturated acids, the process afforded vinyl acetic acid derivatives, involving carboxylation of a terminal carbon of allene moiety, and di-carboxyUc acids. Catalytic double 

To date, little information is available in the literature on catalytic co-oligomerization of allenes with CO2. Allene and CO2 can react in the presence of palladium catalysts to yield linear esters (A and B, Stmcture 5.3) as the main carboxylated products, together with lower amounts of 4,6-dimethyl-2-pyrone (C, Structure 5.3) and a mixture of allene linear oligomers and polymers [87]. 

Structure 5.3 Cooligomerization aiiene-CO2 linear and cyclic esters 

In aromatic solvents, allene and CO2 reacted in the presence of Rh(dppe)(Ti -BPI14) to yield pyrone C (Structure 5.3) besides 1.2.1.2-polyallene and a small amount of oligomers [88]. On the basis of the lack of reactivity of 1-propyne with CO2, under conditions similar to those used for allene, the possibility that pyrone formation could imply a preliminary isomerization of allene to the alkyne can also be excluded in this case. It is worth noting that the pyrone formation requires an 

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The third reaction was related to the hydrocarboxylation of allenes with C02, catalyzed by a tridendate silyl pincer-type palladium complex [108]. In this reaction, a a-allyl palladium species (via hydropallation of allene) was formed, and its trigonal bipyramidal geometry allowed the facile coordination of C02 (presumably in a side-on fashion) and a following nucleophilic addition to realize the carboxylation of allene (Figure 4.16). This reaction proved to be very attractive not only as a C02 fixation reaction, but also as a general method for the synthesis of Py-unsaturated carboxylic acids. 

Allen JR, SA Ensign (1996) Carboxylation of epoxides to 3-keto acids in cell extracts of Xanthobacter strain Py2. J Bacterial 178 1469-1472. 

The second large class of allenes with carbonyl groups as substituents is derivatives of carboxylic acids. Overall, the same principles as with the aldehydes and ketones apply, but not as many examples are known, which might originate in part from the lower acidity of the a-hydrogen atoms of the carbonyl group compared with aldehydes and ketones. 

A number of references cover similar syntheses of allenes with carboxylic acids [131, 139-142] and amides [143] instead of carboxylic esters as electron-withdrawing... 

In the case of carboxylic acids [33], ketones [47] or sulfones [49], it was possible to prove a further prototropic rearrangement of allenes 19 with R2 = H yielding the alkynes 20. In other examples, the prototropic isomerization of the triple bond leads to conjugated dienes directly thus the allene of type 19 could only be postulated as an intermediate [50]. Braverman et al. showed that the allenes generated by prototropic isomerization of dipropargylic sulfones or sulfoxides, for example 24, are unstable. They are transferred rapidly via diradical intermediates to polycycles such as 27 [51-53],... 

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-... 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

A series of allenic carboxylic acids has been converted to funtionalized P-lactones 47 by oxidation-cyclization promoted by pre-prepared solutions of dimethyldioxirane <02T7027>. This transformation is rationalized by the involvement of unisolated spirodioxide intermediates, which give lactones with appropriately situated cx-hydroxyketone moieties. 

The silver-catalyzed cycloisomerization of allenic carboxylic acids to butenolides was also reported by Marshall and co-workers.329 Starting from the enantiomerically enriched propargyl mesylate 390, palladium-catalyzed hydroxycarbonylation led to the chiral allenecarboxylates 391 which afforded the butenolides 392 upon treatment with silver nitrate (Scheme 114). Unfortunately, partial racemization could not be avoided in this two-step sequence. In a related study, Ma and Shi330 have shown that the combination of Pd(PPh3)4 and Ag2C03 promotes the cyclization of allenecarboxylates to the corresponding butenolides, accompanied by the introduction of aryl or alkenyl groups at C3. 

Silver-catalyzed cyclization reactions of allenic carbonyl compounds were applied for the total synthesis of various natural products, including rubifolide,331 kallolide A and B,332,332a and deoxypukalide.333 In their total synthesis of the enantiomer of rubifolide 396, Marshall and Sehon331 took advantage of the silver-catalyzed cycloisomerization of the allenic ketone 393 to the furan 394, as well as of the analogous reaction of the allenic carboxylate 395 to the target molecule 396 (Scheme 115). 

Photoisomerization of ethyl 2-cyano-l,2-dihydroquinoline-l-carboxylate gave allene derivatives, but introduction of a methyl group at C4 of the quinoline changed the reaction course the product was then ethyl e t/o-l-cyano-6b-methyl-l,la,2,6b-tetrahydrocyclopropa[(>]indole-2-carboxylate (en /o-3a). ... 

Anionic oxy-Cope rearrangement of allene alcohol 40 under standard conditions (KH, 18-crown-6, I2, THF, 2 h at 20 °C, in 40% yield) gave rise to the carboxylic acid 41 (equation Treatment of 40 with a catalytic amount of NaOEt (THF, 20 °C, 12 h)... 

Additions to Cyclopentenones and Related Systems. (2 + 2)-Cycloadditions are reported following the irradiation of mixtures of alkyl and aryl 2-thioxo-3/f-benzoxazole-3-carboxylates with alkenes. Cycloaddition also occurs to the CS double bond. The photochemical additions of arylalkenes to 3-phenylcyclo-pentenone and 3-phenyl cyclohexenone have been studied. The regio- and stereochemistry observed in the additions has been rationalized in terms of the stability of the intermediate biradicals. Photocycloaddition of allene to the cyclopentenone derivative (6) in methylene chloride solution at — 78°C affords... 

The experimental conditions for the carboxylation of allenyllithium are governed by the consideration that introduction of the COOLi group renders the allenic protons more acidic (resonance stabilization). If the normal order addition is used (introduction of C02 into the solution of allenyllithium), the allenic carboxylate primarily formed may easily be deprotonated by the strongly basic allenyllithium. The new species (either LiCH=C=CHCOOLi or H2C=C=C(Li)COOLi) may react also with C02. To avoid this situation the solution of allenyllithium is gradually added to a strongly cooled solution of carbon dioxide in THF. As usual, liberation of the acid occurs by adding mineral acid. In view of the possibility of an acid-catalyzed cyclization to a lactone too strongly acidic conditions should be avoided ... 

Among interesting olefin syntheses with ester phosphonates are those with the allenic aldehydes (141) and with the steroidal epoxy-aldehyde (142). The yield of allenic carboxylic esters has been increased to... 

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