Allylation reaction using allenes

Hydroboration of allenes. With few exceptions, the 9-BBN hydroboration of allenes affords B-allylic-9-BBN derivatives. In contrast, the reactions of allenes with disiamylborane or dicyclohexylborane afiord predominantly vinylic boranes. With unsymmetrical allenes, 9-BBN binds to the less substituted carbon atom. Allene itself affords a 1,3-dibora derivative. The B-allylic-9-BBN derivatives are useful reagents for the allylic boration of carbonyl compounds. ... 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

The reaction is very sensitive to metal ion catalysis, particularly by Cu " and Ag", and oxygen inhibits the reaction. Po and Allen studied the uncatalysed reaction in oxygen-free solutions containing 10 M EDTA to ensure that the concentrations of free metal ions were insignificant. Under these conditions the reaction is first order with respect to peroxodisulphate and the rate is essentially independent of oxalate concentration (there is a slight increase in the first-order rate coefficient with increase of oxalate concentration). Allyl acetate inhibits the reaction and reduces the rate to that observed in the absence of oxalate. In the range pH 0.5-10.3 a rate maximum occurs at pH 4.5. The first-order rate coefficient for the reaction using 0.08 M disodium oxalate is expressed by... 

The palladium-catalyzed stannylation of allenes is an efficient approach for the preparation of y-substituted allylic stannanes. williams has recently described the bis-stannylation of 1-methoxymethyleneoxyallene yielding ( )-105, as well as the use of this functionalized stannane in allylation reactions. Pre-organization of the aldehyde by a-chelation provides for the synclinal transition state 108 leading to ant/,yyn-adduct 107 (Scheme 5.2.24). The mild conditions of the reaction retain the alkenylstannane of the product for further elaboration via cross-coupling reactions. 

Cyclopropanadon The Sm-MCjSiCl combination promotes Simmons-Smith reactions on allylic alcohols, including allenic alcohols. Thus, 2-methylenecyclopropyl carbinols are readily obtained. The diastereoselectivity could be affected by using different promoters. 

Cross-coupling carboamination reactions between allenes and 2-haloaniline derivatives or halogenated allylic amines have also been employed for the generation of substituted indolines, and use of an appropriate chiral catalyst for these transformations leads to formation of enantioenriched products [52]. For example, Larock has described the synthesis of indoline 56 via the Pd-catalyzed reaction of aryl iodide 54... 

Cross coupling of a,p-unsaturated alkenes with allenes could also be promoted. The reaction was catalyzed by the complex [CpRu(CH3CN)3]PFg with CeCl3 as a cocatalyst. A ruthenacyclopentane is proposed as an intermediate and this o-allyl complex allowing nucleophilic additions, an alkylative lactonization was carried out by using allenes with tethered carboxylic acid [113] [Eq. (51)]. 

Allenoates are coupled with allylic bromides using a palladium(II) chloride/iron(III) chloride catalyst system (Scheme 4-349). The interaction of iron(III) chloride with the ethoxycarbonyl allene generates a 2-(5/f)-furanonyl iron species, which undergoes transmetalation with palladium(II) chloride and subsequent cross-coupling reaction with allyl bromide affording P-allyl polysubstituted butenolides. ... 

Fujita and co-workers reported the photochemical reaction of allenes in acetic acid. Irradiation (254 nm) of 14a-e affords the respective enol acetates 15. In the reaction of 14b, a triplet mechanism is proposed on the basis of quenching experiments. In methanol solution, on the other hand, the photochemical reaction of tetraphenylaUene 16, using Corex or Pyrex filters, was reported by Klett and Johnson to yield the allylic methyl ether 17 as the major photoproduct along with 18 and 19 (in ratios of 10 1 1). Similar reactions of triphenylallene 20 and 1,3-diphenylallene 21 also afford aUyl ethers 22,23 (5 1), and 24, respectively. In these reactions, a mechanism involving a strongly polarized planar singlet excited state is proposed on the basis of triplet sensitization experiments. 

Roush has crafted a class of allyl/vinyl diboron reagents that participate in sequential aldehyde addition 1,5-anti-diols reactions and enable the expeditious synthesis of 1,5-diols. The hydroboration reaction of allene 34 furnishes 35, treatment of which with aldehydes results in the formation of 36 (Scheme 5.6) [64]. These allylboronate adducts subsequently undergo addition to a second set of aldehydes, generating 1,5-anti-diols 37 with high diastereoselectivity (S 20 1) and optical purity (S 89% ee). Use of the bulkier boronate 38 gives 1,5-syn-diols 39 with equally high stereoselectivity (dr >14 1, ee>91%) [65]. 

The intermediate 190 of the intramolecular aminopalladation of an allenic bond with jV-tosylcarbamate undergoes insertion of allylic chloride. Subsequent elimination of PdCl2 occurs to afford the 1,4-diene system 191. The regeneration of Pd(II) species makes the reaction catalytic without using a reoxidant[190]. 

Aryl or alkenyl halides attack the central carbon of the allene system in the 2,3-butadien-l-ol 120 to form the 7r-allyl intermediate 121, which undergoes elimination reaction to afford the o,/3-unsaturated ketone 122 or aldehyde. The reaction proceeds smoothly in DMSO using dppe as a ligandflOl]. 

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

An intramolecular Pd-catalyzed ring closure of an allylic halide, acetate or carbonate containing an allene moiety as 6/1-256, followed by a Suzuki reaction, was used by Zhang and coworkers for the synthesis of five-membered carbo- and heterocycles 6/1-257 and 6/1-258 (Scheme 6/1.67) [125]. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

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