Allenyl acid

In analogy with the oxybromination reaction of allenyl alcohols, allenyl acids 12 afforded five- and six-membered lactones 13 on treatment with lithium bromide in the presence of palladium acetate (Scheme 17.8) [7, 8],... 

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. 

Scheme 17.12 Cyclization-dimerization of a-allenyl acids and ketones.

Scheme 17.13 Alternative mechanism for the cyclization—dimerization reaction of an a-allenyl acid and a ketone.

In situ epoxidation of allenyl alcohols [20], aldehydes [21], acids [22] and sulfonamides [23] followed by intramolecular ring opening of the intermediates was thoroughly investigated by Crandall and co-workers. They showed that products formed either from the allene oxide or the spirodioxide intermediate can be prepared selectively. Allenyl acids 56, for example, react first with DMDO on their more substituted double bond. When the concentration of the oxidant is low (DMDO is formed... 

When allenyl aldehydes are allowed to react with DMDO, the aldehyde moiety is not oxidized to the acid except for monosubstituted allenes [21]. In all other cases, the carbonyl oxygen participates as a nucleophile in the opening of the intermediate epoxide. From 2,2,5-trimethy]-3,4-hexadienal 67, for example, five different products can be synthesized selectively under different reaction conditions (Scheme 17.22). When p-toluenesulfonic acid (TsOH) is present or DMDO is formed in situ, then the initially formed allene (mono)oxide reacts with the aldehyde moiety to give 68 or 69. In the presence of excess DMDO and the absence of acid, three other products (70-72) can be formed via the spirodioxide intermediate. These reactions, however, seem to be less general compared with similar reactions of allenyl acids and allenyl alcohols. y-Allenylaldehydes 73 can be cyclized to five-membered hemiacetals 74 via the spirodioxide intermediate. 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

In a similar process, nickel compounds also catalyze the carbonylation of allenyl halides, under phase-transfer conditions (PTC), to give allenyl acids in poor to reasonably good yields (equation 94)368. 

The allenyl ketones (271) and (272) are obtained from the allenyl acid fluoride (273) by the action of dimethylcadmium using the more reactive dimethylcopper, the bisalkylated (274) is the product. ... 

A mixture of 100 ml of glacial acetic acid, 15 ml of 30% hydrogen peroxide and 5.0 g of allenyl methyl sulfoxide (see Chapter VII-1, Exp. 1) was heated for 30 min at 100°C. The colourless solution was cooled to 20°C and poured into 300 ml of ice-water. The sulfone was isolated by extracting the solution twelve times... 

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]. 

The equilibrium between propargyl- and allenyl-tin compounds is not spontaneous, but it occurs in the presence of Lewis acids or coordinating solvents, and an ion-pair mechanism has been proposed (159). Substitution by iodine, or addition to chloral, occurs with propargyl/al-lenyl rearrangement (160, 161), analogous to the allylic rearrangement already mentioned. 

TTie solvolysis of propargylic substrates (199) and formation of alkynylcarbonium ions (200) has been extensively investigated. Particularly good evidence for the formation of alkynylcarbonium ions comes from the nuclear magnetic resonance spectra of alkynyl alcohols in strong acid media (200, 201). The downfield shifts of 4ppm for the proton of HC=C— and 1 ppm for CH3C=C- relative to their neutral precursors is indicative of carbonium-ion formation and shows the importance of the allenyl resonance contribution. 

The synthesis of the CG525155 (a neutral endopeptidase inhibitor) required a Pd catalyzed Tsuji-Trost reaction as the key step following the strategy described by Johnson. Starting from the optically active allenyl amino acid methylester 91 (synthesized in several steps from 90), the seco-derivative 92 as the crucial precursor was generated in several steps in high yield. The Pd (0)... 

Intermolecular hydroalkoxylation of 1,1- and 1,3-di-substituted, tri-substituted and tetra-substituted allenes with a range of primary and secondary alcohols, methanol, phenol and propionic acid was catalysed by the system [AuCl(IPr)]/ AgOTf (1 1, 5 mol% each component) at room temperature in toluene, giving excellent conversions to the allylic ethers. Hydroalkoxylation of monosubstituted or trisubstituted allenes led to the selective addition of the alcohol to the less hindered allene terminus and the formation of allylic ethers. A plausible mechanism involves the reaction of the in situ formed cationic (IPr)Au" with the substituted allene to form the tt-allenyl complex 105, which after nucleophilic attack of the alcohol gives the o-alkenyl complex 106, which, in turn, is converted to the product by protonolysis and concomitant regeneration of the cationic active species (IPr)-Au" (Scheme 2.18) [86]. 

The products from the acid-catalyzed hydration of a-tertiary alcohols 30 (Meyer-Schuster and Rupe rearrangements) are formed via the mesomeric propargyl-allenyl cation (equation 9) and have been extensively investigated28. 

Similar to the cycloaddition of allyl cations30, allenyl cations have been found to undergo cycloadditions with alkenes to afford bicyclic compounds31. The allenyl cations were generated from propargyl chlorides by treatment with Lewis acids. This reaction sequence proceeds via the cyclization 34 -------> 3532, in spite of the fact that... 

Pyran-2-ones are formed in high yield through the Pd-catalysed annulation of allenyl stannanes by P-iodo vinylic acids. The reaction, which probably involves a Stille cyclisation sequence, exhibits good selectivity (Scheme 36) <00CC1987>. 

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. 

Burger2 has shown that alkynes undergo both Lewis acid-catalyzed and thermal carbonyl-yne reactions with 3,3,3-trifluoropyruvates to give allenes. Reaction of 1 (Equation (2)) occurs to give a 1 1 mixture of diastereomeric allenyl carbinols 2. Alternatively, reaction of hexyne 1 and methyl trifluoropyruvate with MgBr2-OEt2 at low temperature afforded 2 as an 8 1 mixture of diastereomers. The thermal reaction does not suffer from allylic alcohol byproducts arising from reaction of the substrate with the Lewis acid.3... 

The use of tartrates as chiral auxiliaries in asymmetric reactions of allenyl bor-onic acid was first reported by Haruta et al.69 in 1982. However, it was not for several years that Roush et al.,70 after extensive study, achieved excellent results in the asymmetric aldol reactions induced by a new class of tartrate ester based allyl boronates. 

Closely related to both allyl carbenoids and the allenyl carbenoids discussed above, propargyl carbenoids 101 are readily generated in situ and insert into zirconacycles to afford species 102 (Scheme 3.27), which are closely related to species 84 derived from allenyl carbenoids [65], Protonation affords a mixture of allene and alkyne products, but the Lewis acid assisted addition of aldehydes is regioselective and affords the homopropargylic alcohol products 103 in high yield. Bicydic zirconacyclopentenes react similarly, but there is little diastereocontrol from the ring junction to the newly formed stereocenters. The r 3-propargyl complexes derived from saturated zirconacycles are inert towards aldehyde addition. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

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