Ketones, allenyl

The 4-kcto group in the alkyne 262 as an enol form adds to the triple bond to give the furan 263[133], Even the conjugated keto alkyne 264 was converted into the furan 266 via isomerization to the allenyl ketone 265[134],... 

Disubstituted furans 62 are obtained from a gold-catalyzed cycloisomerization/dimerization pathway involving terminal allenyl ketones and a,(3-unsaturated ketones <00AG(E)2285>. 

Table 11 Palladium-catalyzed silastannative cyclization of allenyl ketones...

Entry R RCOZr/ R /propargyl halide 1,4- allenyl ketone dicarbonyl Yield (%) Yield (%) ... 

The formation of an allenyl ketone as the sole product can be achieved by using an excess (2 equiv.) of propargyl bromide (entries 3—6, Table 5.9). Use of an increased amount (3 equiv.) of the acylzirconocene chloride in the reaction with propargyl bromide and/or tosylate yields a significant amount of a 1,4-dicarbonyl compound derived from Michael-type addition of the acylzirconocene chloride to the initially formed allenyl ketone (entry 2, Table 5.9). The Michael-type addition of acylzirconocene chlorides to allenyl ketones under Cu(I)-catalyzed conditions has been confirmed by an independent experiment (Scheme 5.31). 

Scheme 5.31. Cu(l)-catalyzed Michael-type addition to an allenyl ketone.

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 latter mode of reaction has even been reported to proceed in presence of sil-ver(I) ions [127], which is not easy to understand in the context of Marshall s silver-catalyzed cycloisomerization of allenyl ketones (see Chapter 15). 

A unique photochemical rearrangement in which an o-alkynylphenol is isomer-ized to an allenyl ketone has also been reported [129]. 

Acylzirconocene chlorides 78, which are easily available through the hydrozirco-nation of alkenes or alkynes with Cp2Zr(H)Cl and subsequent CO insertion, can be used as acyl anion equivalents Cu(I)-catalyzed reactions with propargyl compounds 77 afford allenyl ketones 79 (Scheme 3.40) [86]. The use of an excess of 77 (2 equiv. to 78) is important for the selective preparation of 79, which prevents an undesirable side reaction of the allenic products 79 with 78. 

The Doering-Moore-Skattebol method including a cyclopropylidene-allene rearrangement is often used for the synthesis of allenes. However, the reaction conditions applied are often not compatible with acceptor substituents. One of the rare exceptions is the transformation 76 —> 77 (Scheme 7.11) [122]. The oximes 77 are not accessible by the classical route starting from allenyl ketone and hydroxylamine (see Section 7.3.2). 

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],... 

The AlCl3-mediated acylation of but-l-en-3-ynes such as 106 to give mixtures of allenyl ketones of type 107 and 1,2-addition products such as 108 have been published several times (Scheme 7.16) [144, 145]. In the case of other substitution patterns of the starting enynes, the stereochemistry of the resulting allenyl ketones was investigated [146]. 

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]. 

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]. 

The analogous transformation of 125, also realized by flash vacuum pyrolysis, gave rise to allenic oximes 126 [165], which are not directly accessible by the classical route starting from allenyl ketones and hydroxylamine (see Section 7.3.2) [122], Because compounds 125 are prepared from allenyl ketones and furan by [4 + 2]-cycloaddition followed by treatment with hydroxylamine, the retro-Diels-Alder reaction 125 —> 126 is in principle the removal of a protecting group (see also Scheme 7.46). 

X = CH(OH)R] to butadienals [166-168] and allenyl ketones [137, 169-171], respectively. Using particularly the Swern or Dess-Martin oxidation methods, very high yields can be achieved [166, 172,173],... 

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 nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

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]. 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

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-... 

Particularly good yields of the cydoadduct 329 are obtained if R1 = R2 = H is valid for the allenyl ketone 328 [165]. The Diels-Alder products 329 can undergo many chemical transformations, for example to the oximes 330, which yield the modified allenes 331 after a subsequent flash vacuum pyrolysis. The oximes 331 generated by retro-Diels-Alder reaction are not available from ketones 328 and hydroxylamine hydrochloride directly [122] (see also Scheme 7.19). 

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... 

If epoxidation is accepted as [2 + l]-cydoaddition, then the rare transformation of an allenyl ketone to an isolable allene oxide should be mentioned [170]. The Pau-son-Khand reaction, probably the best known of the [2 + 2 + l]-cycloadditions, can also be performed using an alkyne and an allene, the latter replacing a simple alkene. These reactions were summerized recently by Brummond also induding acceptor-substituted allenes [361]. 

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). 

Marshall et al. noted that under the catalysis of Ag+ or Rh+, 1,2-allenyl ketone or aldehyde 417 may undergo cycloisomerization to afford furans 418. The reaction proceeded via the interaction of Ag+ or Rh+ with the relatively electron-rich C=C bond in the allene moiety followed by nucleophilic attack of the carbonyl oxygen [187]. Through a labeling study, it was found that the reaction proceeds by the mechanism shown in Scheme 10.162 [188]. 

Due to the strong electron-withdrawing ability of the carbonyl group, a 1,2-allenyl ketone is a very good Michael acceptor. Hence it can undergo 1,4-addition with all kinds of nucleophiles. 

Similar 1,2-addition reactions were also observed in the reaction of 2,3-allenal with organolithiums, Grignard reagents or the reduction of 1,2-allenyl ketones with metal hydrides [190],... 

Recently, Hanzawa et al. reported that, catalyzed by Cu(II), the reaction of an acylzirconium with propargyl bromide affords 1,2-allenyl ketones 428, which may undergo a further conjugate addition with acylzirconocene to give 2-methylene 1,4-diketones 429 [191],... 

The reaction of 1,2-allenyl ketones with organocuprates afforded /3,y-unsaturated enones. The reaction with mixed cuprates RR CuLi delivered, depending on the properties of R and R, two products 430 and 431 [192]. 

Under the catalysis of MeONa, MeOH can react with 1,2-allenyl ketones to give /i-methoxy-/3,y-unsaturated enones 441, which undergo migration of the C=C bond to afford the more favorable /3-methoxy-a,/3-unsaturated enones [197-199]. 

It is interesting that the reaction of triphenylphosphine with a 1,2-allenyl ketone leads to the formation of a vinyl phosphonium salt 449, which upon protection of the carbonyl group would accept nucleophilic attack followed by elimination in the presence of Et3N to afford y-nudeophile substituted- ,/j-unsaturated enones 451 [197]. 

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