Allenes, 1,3-disubstituted

Into the previously reported transition-metal catalyzed intermolecular hydroalk-oxylations of alkenes, gold catalysts showed to be the most active catalysts, with divergent reactivity with respect to PtCl2, leading to the formation of aUylethers [156]. Opposite to monosubstituted allenes, disubstituted aUenes yield no aliphatic acetals. Deuteration studies support the hypothesis of a zwitterionic Pt carbene as... 

If two equivalents of the reagents are used, disubstitution to ECeC-CH(E)R occurs in most cases, but interestingly the reaction of LiCeCCH(Li)R with an excess of COj gives mainly the allenic dicarboxylic acids. These are probably the result of a rapid isomerization of the primary dilithium salt of the acetylenic diacid during the work-up or during the reaction of the dilithio compound with COj ... 

The nonplanarity of allenes has an interesting stereochemical consequence 1 3 Disubstituted allenes are chiral they are not superimposable on their mirror images Even an allene as simple as 2 3 pentadiene (CH3CH=C=CHCH3) has been obtained as sep arate enantiomers... 

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. 

Unsaturated substituents of dioxolanes 36-38 and dioxanes 39-41 are prone to prototropic isomerization under the reaction conditions. According to IR spectroscopy, the isomer ratio in the reaction mixture depends on the temperature and duration of the experiment. However, in all cases, isomers with terminal acetylenic (36, 39) or allenic (37, 40) groups prevail. An attempt to displace the equilibrium toward the formation of disubstituted acetylene 41 by carrying out the reaction at a higher temperature (140°C) was unsuccessful From the reaction mixture, the diacetal of acetoacetaldehyde 42, formed via addition of propane-1,3-diol to unsaturated substituents of 1,3-dioxanes 39-41, was isolated (74ZOR953). 

This method provides a convenient synthesis of alkenes with the double bond in a relatively unstable position. Thus reduction of the p-toluenesulfonylhydrazones of a,(3-unsaturated aryl ketones and conjugated dienones gives rise to nonconjugated olefins. Unsaturated ketones with endocyclic double bonds produce olefins with double bonds in the exocyclic position. The reduction of p-toluenesulfonylhydrazones of conjugated alkynones furnishes a simple synthesis of 1,3-disubstituted allenes. ... 

Under the same reaction conditions, -keto esters which have been alkylated on the a-carbon atom (thus leading to 3,4-disubstituted 5-pyrazolones upon treatment with hydrazine) give allenic esters in good (50-70%) yield (158). The mechanism (Scheme 36) again appears to involve thallation of the enamine tautomer of the 5 -pyrazolone, but deprotonation now takes place... 

In 2009, Ritter and coworkers reported a selective Fe-catalyzed hydroboration of 1,3-dienes to produce linear ( )-y-disubstituted allylboranes under mild conditions when a combination of Ll-FeCl2 and magnesium metal as a catalyst was used. Tbe branched ( )-allylboranes were obtained by using L2-FeCl2 instead of Ll-FeCl2 (Scheme 26) [88]. For the synthesis of 2-borylallylsilanes, this method was superior to the previously reported silaboration of allenes [89]. 

Interestingly, in the case of enantiomerically pure internal allenes, a diastereose-lective IH is observed (e.g.. Scheme 4-17), as shown by the catalytic hydrogenation of the Z/E mixture to give the trans-2,5-disubstituted pyrrolidine as a single compound. 

A sequential 1,2-dechlorination/S - S bond fission of the 3,4-disubstituted 2-butenoate 49 is performed by cat. PbBr2/Al in DMF, giving the 2-exo-methylenepenam 51 through the allene intermediate 50 (Scheme 30) [70]. 

Allenynes 160 were also cyclized chemo- and regioselectively to methylen-eyclopentane derivatives 161 and 162 using Rh(acac)(CO)2 as the catalyst and silanes or alkoxysilanes as the reductant (Eq. 32) [96]. The major product resulted from initial insertion of the internal Jt-bond of the allene into the Rh-Si bond. Only 1,1-disubstituted allenes were used for this reaction others may show less selectivity for the internal Jt-bond of the allene. 

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

Allenes add nitrile oxides either to one or two double bonds. For mono- and 1,1-disubstituted allenes, relative activity of the two bonds depends on the nature of substituents. The reaction (Scheme 1.18) of N-propadienylanilines 54 with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide proceeds site- and regioselectively to give 5-substituted 4-methylene-4,5-dihydroisoxazoles 55, which add a second molecule of nitrile oxide to afford 4,5/-spirobi-(4,5-dihydroisoxazoles) 56. Dihy-droisoxazoles 55 isomerize to 4-(2-aminobenzyl)isoxazoles 57 via a Claisen-type rearrangement (224). 

Trost et alJ2 also explored the compatibility of di-, tri-, and tetrasubstituted allenes with their intermolecular Alder-ene protocol. Multiple substituents present the opportunity for a mixture of products to arise from differing regio- and chemoselectivity. 1,1-Disubstituted allenes were coupled to methyl vinyl ketone with excellent chemo-selectivity only when one set of /3-hydrogens was activated by an cy-ester or amide (Equation (69)). If the /3-hydrogens were of similar acidity, a mixture of products was obtained, as in the coupling of allenol 103 with methyl vinyl ketone dienes 104 and 105 are produced in a 1.3 1 mixture (Equation (70)). 

On the other hand, platinum-catalyzed silaboration of allenes results in an opposite regiochemical preference. Silaboration of a 1,1-disubstituted allene affords terminal addition product regioselectively in the presence of a platinum catalyst, whereas the internal addition product is obtained with a Pd2(dba)3-PPh3 catalyst (Scheme 49).227... 

The intramolecular competition of two propargylic alkoxy groups, one on each side of the alkyne, is interesting. In a series of substrates related to 94 [180], always the 1,2-disubstituted allene 95 (Scheme 1.41) and not a 1,1,3-trisubstituted allene is formed (see also [225, 226]). The opposite regioselectivity was described in one publication (deprotonation with tBuLi, then protonation), but the allenes described there proved to be labile and quickly converted to other products [227]. 

A variety of optically active 4,4-disubstituted allenecarboxylates 245 were provided by HWE reaction of intermediate disubstituted ketene acetates 244 with homochiral HWE reagents 246 developed by Tanaka and co-workers (Scheme 4.63) [99]. a,a-Di-substituted phenyl or 2,6-di-tert-butyl-4-methylphenyl (BHT) acetates 243 were used for the formation of 245 [100]. Addition of ZnCl2 to a solution of the lithiated phos-phonate may cause binding of the rigidly chelated phosphonate anion by Zn2+, where the axially chiral binaphthyl group dictates the orientation of the approach to the electrophile from the less hindered si phase of the reagent. Similarly, the aryl phosphorus methylphosphonium salt 248 was converted to a titanium ylide, which was condensed with aromatic aldehydes to provide allenes 249 with poor ee (Scheme 4.64) [101]. 

Subsequent addition of aryl Grignard reagents then provides the secondary alcohols 161, which easily undergo elimination under the conditions shown in the scheme to provide the 1,3-disubstituted allenes 162 in excellent yields (-90%). 

Even the reaction with 1,1-disubstituted allenes delivered 2-chloroallyl alcohols 16 with the hydroxyl group connected to the more substituted terminus [15]. 

The reaction of disubstituted 2,3-allenals 434 with primary amines leads to the predominant formation of 1,2-allenylimines in THF, CC14, toluene, etc. [194],... 

The attempt of chiral induction in the cross-coupling of racemic l-bromo-4,4-di-methyl-l,2-pentadiene (22b) with PhZnCl in the presence of the chiral palladium complex Pd (R,R)-DIOP 2 was disappointing. Although the expected disubstituted allene 23 was formed in quantitative yield, the enantiomeric excess was at best 9% ee [15]. 

Marks et al. s organolanthanide catalysts show a strong dependence on the substitution of the allene [99]. Terminal allenes 144 with three carbons in the tether deliver the tetrahydropyridines 145. 1,2-Disubstituted allenes with the same length of the tether lead to the vinylpyrrolines 146 (Scheme 15.45). 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

Exposure of a monosubstituted allene to a Grubbs carbene complex allows the formation of a 1,3-disubstituted allene accompanied with polymers (Scheme 16.93) [99]. The product distribution depends considerably on the alkyl substituents on the allene moiety and particularly the reaction of a series of phenylallenes undergoes complete conversion to polymers. 

Using TEBA-CI. + trace of 1,3-disubstituted indole. + 1,3-disub-stituted indole (15%).d + 1,3-disubstituted indole (5%).1 + 3-isomer (15%) and 1,3-disubstituted indole 122%). l-allylindole (87%) and 1,3-diallylindole (9%) obtained, when a stoichiometric amount of catalyst is used. + 3-isomer (10%) and 1,3-disubslilutcd indole (21%). at 20°C. + allene derivative (2%). 

Monomers with cumulated double bonds, such as substituted allenes and ketenes, produce a great variety of structures. Stereoisomerism is found both at the saturated (iso- or syndiotacticity) and at the unsaturated carbons where the substituents in the plane of the chain can be oriented in either direction (forward or backward). With regard to 1,3-disubstituted allenes, four stereoregular strac-tures, 43-46 (Scheme 10), are predicted. Porri, Rossi, and Ingrosso succeeded in polymerizing 2,3-pentadiene (1,3-dimethylallene) samples of different optical purity (87). In their experiments they recognized the existence of sequences 43. 

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-... 

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