Allenyl ketone intermediate

Pd-catalyzed isomerization of ynones to furans has been an active area of research over the last decade. Huang et al. described a Pd-catalyzed rearrangement of a,P-acetylenic ketones to furans in moderate yield [102], For example, Pd(dba)2 promoted the isomerization of alkyne 124 to a putative allenyl ketone intermediate 125, which subsequently cyclized to the corresponding furan 126. 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

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-... 

Tius and co-workers investigated a number of cationic cyclopentannelations of allenyl ethers [113] and found that 1-lithio-l-alkoxyallenes 180 react with a,/3-unsatu-rated carbonyl compounds 181 leading to highly functionalized cyclopentenones 182 (Scheme 8.44). The primary products are a-allenyl ketones 183, which form pentadienyl cations 184 by protonation. The latter undergo a thermally allowed 4jt-conrotatory ring closure to intermediates 185, which with elimination of R1 finally lead to the expected products 182 (Scheme 8.45). 

The intermediate 452 resulting from the direct reaction of PPh3 with an allenyl ketone can also serve as an all-carbon 1,3-dipole to undergo [8 + 2]-annelation with tropone to yield fused bicyclic tetrahydrofuran derivatives 455 [203]. 

The reactivity of allenyl ketones is also manifested in the Hg(II)-catalyzed ipso substitution that converts 54 to spirodione 55 (Eq. 13.17) [19]. The reaction presumably involves activation of the allene by Hg(II), followed by intramolecular electrophilic attack on the aromatic ring. Hydrolytic cleavage of the metal from the intermediate product of the reaction, followed by rearrangement leads to the observed spirocyclic dione. 

The reaction of an allene with an aryl- or vinylpalladium(II) species is a widely used way of forming a Jt-allyl complex. Subsequent nucleophilic attack on this intermediate gives the product and palladium(O) (Scheme 17.1). Oxidative addition of palladium ) to an aryl or vinyl halide closes the catalytic cycle that does not involve an overall oxidation. a-Allenyl acids 27, however, react with palladium(II) instead of with palladium(O) to afford cr-vinylpalladium(II) intermediates 28 (Scheme 17.12). These cr-complexes than react with either an allenyl ketone [11] or with another alle-nyl acid [12] to form 4-(3 -furanyl)butenolides 30 or -dibutenolides 32, respectively. 

In constrast with intermolecular nitrone cycloadditions to alkynes and allenes, very little work has been done on the corresponding intramolecular cycloadditions. The bicyclic isoxazolidines (65a-b) were reported as products from reaction of an alkynone with methylhydroxylamine in ethanol.26b Presumably the initial strained bridgehead C—C double bond of the AMsoxazoline added ethanol under the reaction conditions. Cyclization of an allenyl ketone with methylhydroxylamine in ethanol solution also led to isoxazolidines (65a-b) as the major products and isoxazolidine (66) as a minor product.266 Thus, preferential cyclization to the internal C—-C double bond of the allene occurred followed by addition of ethanol to the exocyclic C—C double bond of the methyleneisoxazolidine intermediate. 

The acylpalladium complex as the intermediate of the carbonylation can be trapped by active methylene compounds to give allenyl ketones without forming methyl esters. 

Allenic products ate formed in the anion-initiated rearrangement of cyanohydrin propargylic ethers (148 Table 10).- The intermediate cyanohydrins (149) are converted to allenyl ketones (150) upon work-up. 

Reduction of Cp2TiCl2 with Mg in the presence of propargyl acetates gives allenyl Ti intermediates which react with nucleophilic reagents such as aldehydes, ketones, acetonitrile, and allyl bromide to give carbon-carbon bondforming products in moderate yields.1149... 

In 1997, Hashmi et al. observed the Pd-catalyzed homodimerization of 1,2-allenyl ketones affording2-substituted4-(4 -oxo-2 -alken-2 -yl)furans (Scheme 31) [23]. The reaction may proceed via intramolecular oxypalladation involving the carbonyl oxygen, leading to the formation of furanylpalladium intermediate 69, followed by intermolecular carbopalladation with a second molecule of 1,2-allenyl ketone. Protonation of the C-Pd bond in 70 afforded the product 66 and regenerated Pd(II) (Scheme 32). 

The same researchers also reported a very facile cycloisomerization reaction of allenyl ketones 15 into furans 16 in the presence of gold(III) catalyst (Scheme 8.7) [46, 103-112]. Furthermore, the authors extended this reaction to the cydoisomeriza-tion-addition cascade process of allenyl ketones 15 with enones 17 to produce 2,5-disubstituted furans 18 (Scheme 8.8) [111]. Formation of the latter products was rationalized via two proposed pathways. According to path A, fiiran intermediate 16 undergoes an auration with Au(III)-catalyst to produce the furyl-gold species, which, upon subsequent 1,4-addition to the Michael acceptor 17, generates intermediate 19... 

The second communication of that year [24] is now cited more than 225 times, which also represents a remarkable number. This communication also comprised new reactivity patterns (Scheme 2). Based on the results from the first communication discussed above, a furan ring is formed from an allenyl ketone. Then the furanyne intermediate underwent a previously unknown transformation to an annelated phenol. Since they are easily accessible, furanynes can also be used directly. 

DFT study of interception of the allenyl enolate intermediate of Meyer-Schuster rearrangement using aldehydes and imines has shown that the active form of the vanadium catalyst bears two triphenyl siloxy ligands and that vanadium enolate is directly involved in the C-C bond formation." DFT calculations have elucidated the mechanisms and diastereoselectivities of phosphine-catalysed [4-1-2] annulations between allenoates and ketones or aldimines (Scheme 44). 

Arylative or silylative cyclizations of allenyl aldehydes or ketones have been reported (Equations (101) and (102)).459,459a The intermolecular process, that is, three-component coupling reaction of aldehydes, allenes, and arylboronic acids, is catalyzed by palladium as well (Equation (103)).46O 46Oa These reactions are proposed to proceed through nucleophilic attack of the allylpalladium intermediates to the carbonyl groups. 

Moreover, propargyl oxiranes 202 were found to react with samarium diiodide and ketones to form a,a -dihydroxyallenes 203 with moderate to high anti-diastereo-selectivities (Scheme 2.62). Aurrecoechea and co-workers [99] reported this reductive coupling to proceed smoothly in the absence of a palladium catalyst, i.e. a direct electron transfer from the samarium(II) to the substrate has to take place in order to generate an allenyl/propargyl samarium intermediate of type 184/185, which is then regioselectively trapped by the electrophile. 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

The first examples of a Michael-Stork enamine addition to allenyl esters and ketones R1CH=C=C(R2)COX (X = alkyl, alkoxyl) has been reported. Mechanistic investigation revealed that 2 equiv. of enamine are required for optimum yields. In the case of an allenyl methyl ketone, cyclopentyl enamine addition afforded 8-oxobicyclo[3.2.1]octane, providing evidence for the in situ formation of an enamine intermediate following the initial Michael-Stork reaction.187... 

The dehydrogenation of bis(a-bromobenzyl) sulfide (41) with Fe2(CO)9 in the presence of furan affords (43). The iron-stabilized sulfur ylide (42) has been proposed as intermediate. Reaction of C -di-phenylnitrone (44) with l,2-bis(methylene)-3,3.4,4,5,5-hexamethylcyclopentane (45) in benzene at 80 C gives a [4 -I- 3] cycloadduct (46 18%), along with some other products. Landor et al. have shown that the dehydrobromination of allenyl bromide (47) in the presence of furan affords bicyclic ketone (49) in 9% yield. Apparently, a strain alkyne intermediate reacts with r-butyl alcohol to afford an enol ether (48), which is then converted to (49) (Scheme 11). 

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