From allenic substrates

From allenic substrates, with organocopper reagents... 

Vinylepoxides from Other Substrates 9.1.5.1 From Allenes... 

Mikami and Yoshida extended the scope of this method considerably by using propargyl phosphates and chiral proton sources [94], The propargylic phosphates thereby have been found to be advantageous owing to their high reactivity towards palladium and the extremely low nudeophilicity of the phosphate group [95]. In some cases, it was even possible to obtain allenes from primary substrates, e.g. ester 194 (Scheme 2.60) [96]. A notable application of this transformation is the synthesis of the allenic isocarbacydin derivative 197 from its precursor 196 [97]. 

Flypothetical interactions of a five-subsite enzyme with a maltotetraose substrate shown initially with a terminally radiolabeled (filled circles) nonreducing end. The vertical arrow indicates the glycosyl bond cleavage region the roman numerals indicate the subsites, and the 4 indicates the chain length. Only three binding interactions lead to hydrolysis IV,4 V,4 and Vl,4, and their different associated rate constants emphasize that the rates of hydrolysis need not be identical. From Allen and Thoma with permission of the Biochemical Society (London). 

In contrast to the efficient reactions illustrated above, the use of 1,2-disubstituted aikenes as the 2n -components in the [5-1-2] cycloaddition has resulted, thus far, in low cycloadduct yields and complex mixtures, putatively arising from an intermediate metal-lacycle through competitive yS-hydride elimination. This limits access to the carbocyclic cores of some large and medicinally interesting natural product families (for example, those in Scheme 13.3). Introduction of an allene substrate, however, circumvents this limitation by installing the needed carbon-carbon bond while simultaneously leaving a handle for further functionalization (Scheme 13.10). For example, reduction of the exo-... 

Esters. Reductive carbonylation in the presence of an alcohol or phenol leads to an ester. Substrates include organoiodonium salts and allylic alcohols. p,y-Unsaturated thioesters can be generated by the method or from allenes. Note that y-lactones are formed when allylic alcohols are carbonylated without additives. ... 

Although the endothermicity of the 1- 2 interconversion may be overcome both photochemi-cally and thermally (see below), it is only by photoisomerization that cyclopropenes have been prepared from allenes in isolable amounts. As shown in the table below, the allene-cyclopropene rearrangement has been employed predominantly for the preparation of highly substituted and bicyclic cyclopropenes, respectively. It appears that the ring strain of the starting cycloal-lenes is a prerequisite for the success of the interconversion. Furthermore, in order to suppress [2 + 2] cyclodimerization of the substrates a bulky substituent in the cyclic or acyclic precursor is necessary. Low reaction temperatures serve the same purpose. 

During the last few years, more efficient reagents for transforming alkynes into allenes have been developed and even an enzyme catalysed reaction has been investigated The main mechanistic development has been the solution to the problem of whether rearrangements of an alkyne into an allene (and vice versa) involve an intermediate carbanion, or if the reaction can occur via a concerted mechanism in which a proton is donated from the solvent synchronously with the abstraction of a proton from the substrate by a base. 

The first gold-catalyzed addition reactions of carbon nucleophiles to allenes were only first disclosed in 2006, and the number of examples is still small. Toste and co-workers showed that allenic silyl enol ethers undergo a 5-endo- ng cyclization to hexahydroindenone derivatives in the presence of a cationic gold catalyst (Scheme 4-10). In these transformations, water or methanol is used as an external proton source for protodeauration of an intermediate vinylgold species. In an analogous manner, cyclopentenes were obtained in good yields from allenic P-ketoesters. In the presence of a palladium catalyst and an allylic halide, these substrates afford functionalized 2,3-dihydroflirans. 

In an effort to extend tins reactivity to alkenes from allenes, the Toste group [300] performed the cyclohydroamination reaction with their preferred gold catalyst systems using diene-substituted suhbnylamides. Such substrates are prone to proton-mediated reactivity profiles, as discussed earlier, and generation of an acidic species has been postulated for catalytic turnover in Au(I)-catalyzed reactions [300],... 

As in the case of the base-catalyzed reaction, the thermodynamically most stable alkene is the one predominantly formed. However, the acid-catalyzed reaction is much less synthetically useful because carbocations give rise to many side products. If the substrate has several possible locations for a double bond, mixtures of all possible isomers are usually obtained. Isomerization of 1-decene, for example, gives a mixture that contains not only 1-decene and cis- and franj-2-decene but also the cis and trans isomers of 3-, 4-, and 5-decene as well as branched alkenes resulting from rearrangement of carbocations. It is true that the most stable alkenes predominate, but many of them have stabilities that are close together. Acid-catalyzed migration of triple bonds (with allene intermediates) can be accomplished if very strong acids (e.g., HF—PF5) are used. If the mechanism is the same as that for double bonds, vinyl cations are intermediates. 

Allen (106) also studied cobalt hydroformylation with a polymer-bound catalyst. The polymer was formed from diphenyl-p-styrylphosphine cross-linked with divinylbenzene. 2-Hexene was the substrate, and reaction conditions were 175°C and 1500-3000 psi of 1/1 H2/CO. The product aldehyde was 55% linear, and the effluent product solution contained 20-50 ppm cobalt. 

Hydride-promoted reactions are also well known, such as the acrylic and vinylacrylic syntheses (examples 7-10, Table VII). Some less-known compounds, which form in the presence of halide ions added to tetracar-bonylnickel, have been described by Foa and Cassar (example 11, Table VII). Reaction of allene to form methacrylates, and of propargyl chloride to give itaconic acid (via butadienoic acid), have been reported (examples 13 and 14, Table VII). 1,5-Hexadiene has been shown to be a very good substrate to obtain cyclic ketones in the presence of hydrogen chloride and tetracarbonylnickel (example 15, Table VII). The latter has also been used to form esters from olefins (example 16, Table VII). In the presence of an organic acid branched esters form regioselectivity (193). 

An allene moiety can serve as a nucleophile vis-a-vis a 7r-allylpalladium species generated from an allylic acetate moiety in substrates such as 495 (Scheme 124). The cyclization involving these two moieties generates another 7r-allyl intermediate, and the stage is set for the subsequent carbonylative cascade process as demonstrated by the transformation of 495 to 496.402... 

Rhodium complexes catalyze hydrosilylation-cyclization of 1,6-allenynes in the presence of (MeO SiH.77 To avoid complex product distributions, the use of substrates possessing fully substituted alkyne and allene termini is imperative. As shown in the cyclization of 1,6-allenyne 62a, the regiochemistry of silane incorporation differs from that observed in the rhodium-catalyzed hydrosilylation-cyclization of 1,6-enynes (see Section 10.10.2.3.2). For allenyne substrates, allene silylation occurs in preference to alkyne silylation (Scheme 40). 

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... 

As mentioned in the Introduction, this chapter focuses on reactions that deliver allenes as the product. The principles discussed in Sections 1.2.1-1.2.9, of course, also allow the synthesis of allenes as reactive intermediates, which due to other functional groups that are present, undergo further reactions in situ. The most important examples here are base-catalyzed isomerizations to furans [347, 348] ring transfer reactions of propargylic ethers or amines [216, 349-371] and enyneallene cycliza-tion reactions starting from propargylic sulfones [372-375] and related substrates [376, 377]. Details are discussed, for example, in Chapters 16 and 20. 

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