Allenes functionalized

M. G. Allen, Functioning Mycorrhizae, Chapman Hall, New York, London, 1992. 

Coupling of excess (Z)-l,2-dichloroethene (217) with propargyl alcohol first led to the enyne 218, which, when subjected to a second Pd-catalyzed coupling step with trimethylsilylacetylene, provided the mixed diacetylene 219. With all carbon atoms assembled, the allene function was generated by first producing the (unprotected) hydrazine derivative 220, which on treatment with either diethyl azodicarboxylate (DEAD) or 4-methyl-l,2,4-triazoline-3,5-dione (MTAD) under anaerobic conditions at 0 °C yielded the hydrocarbon 27. According to mechanistic studies, the latter process leads first to a mixture of ( )- and (Z)-diazenes. Sigmatropic elimination of... 

R. V. Williams, K. Chanau, /. Chem. Soc., Chem. Commun. 1991,1672—1673 adducts of type 279 are also obtained in very good yield when arylallenes are added in the presence of a cation radical catalyst to permethyl-cydopentadiene, i.e. the allene functions as the dienophile here, see M. Schmittel,... 

Scheme 11.17 Diastereoselective formation of a tetrahydrofuran nucleus via 5-exo-trig alkyl radical cyclization on to an allene functionality in the course of a total synthesis of (+)-samin (56) [75], a)33 67 mixture of diastereomers.

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

Allenylsilanes 159 (Eq. 13.53) and 161 (Eq. 13.54) differ in the axial stereochemistry of the allene function. In each case, formation of the benzyl imine, followed either by treatment with tin(IV) chloride in benzene at room temperature or heating in toluene, leads to diastereomeric products 160 and 162 [63], Significantly, there is no crossover, pointing to a concerted (or fast, stepwise) process. Since the absolute stereochemistry of the allenylsilanes is easily controlled, the methodology is ideal for applications in total synthesis. Weinreb and co-workers have used the reaction for his synthesis of the marine natural product (-)-papuamine. 

As is the case for Diels-Alder cycloadditions, the high reactivity of the allene function provides low activation barrier pathways for a number of synthetically useful ene reactions. 

N-Allenylazetidinone 181 rearranges to cephalosporin 182 in the presence of lithium chloride (Eq. 13.62) [70], This is a very unusual reaction that is presumed to be initiated by chloride ion-induced cleavage of the disulfide to give sulfenyl chloride 183. Thiolate attack at the allene sp carbon atom of 183 generates ester enolate 184, which cyclizes to 182. The reactivity of the allene function in 181 ensures the success of the reaction. 

Allenes have also been used as substrates in free radical cyclizations. Dener and Hart demonstrated that such entries are valuable in constructing pyrrolizidine and indolizidine ring systems [71]. In a total synthesis of pyrrolizidine base (+)-heliotri-dine (340), compound 338 possessing an allene functionality was used as a key intermediate (Scheme 19.62). Tri-n-butyltin radical-mediated carbon-selenium bond homolysis of 338 followed by the addition of the free radical to the allene moiety... 

Other unsaturated esters include cinnamates [68,69] and phenylpropiolates (triple bond) [70], Esters with allenic functionality like 58 have been reported to afford the ortho product 59 in 4% yield (Scheme 22) [71],... 

The benefidal effect of an allene functionality for the construction of bicy-clo[5.3.0]decadienones is evident from the failure of the 1,8-enyne 33 to undergo conversion to 34, to thereby produce the same skeleton (Eq. 6) [20b]. 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

Alcohols will add to allenes in the presence of trace amounts of acids to give vinyl ethers (or acetals) or allylic ethers.401 Analogous to the hydration of allenes, protonation occurs on the terminal carbon of the allenic functionality in 1,2-propadiene, 3-alky 1-1,2-propadienes and 1,3-dialkyl- 1,2-propadienes (equation 248).402 Addition of an alcohol to the resulting vinylic cation produces a vinylic ether, which may on further reaction form an acetal of the corresponding ketone. 

A synthesis of the Inhoffen-Lythgoe diol (46.7, Scheme 2.46), a useful intermediate in the synthesis of Vitamin D derivatives, demonstrates the use of a chiral acetal in an asymmetric tandem cyclisation reaction.102 Once again, Lewis acid co-ordination to the less hindered oxygen of the acetal 46.1 initiated a Prins-like cyclisation that terminated by attack of the propargylsilane on an incipient tertiary carbocation. After removal of the chiral auxiliary, the allene function in the alcohol 46.4 was transformed into the side chain of 46.7 with the creation of two new stereogenic centres. 

The reaction of allenylsilanes with electron deficient ir-systems constitutes a powerful and general method for the tegio- and stereo-selective preparation of substituted cyclopentenes. As first reported, (trimethylsilyl)allenes function as three-carbon nucleophiles in TiCU-promoted (trimethylsilyl)cyclopen-tene annelations (Scheme 31). The annelation process involves the polarization of an a,p-unsaturated carbonyl compound by TUTU to generate an alkoxyallylic cation. Regiospecific electnqrhilic substitution of this cation at C-3 of the allenylsilane produces a silicon-stablizied vinyl cation. A 1,2-shift of the tri-... 

Alkenylenones have not been as widely utilized as the corresponding 2- and 3-alkenylenones. The photocycloaddition of various allenes attached to cyclohexenones and cvclopentenones at the 4-position has been reported and two examples are shown. Irradiation of the cyclopentenone 1 resulted in the formation of the straight adduct 2 and product 3 in a 1 1 ratio140. Compound 3 is formed by reaction across the 1,2-double bond of the allene function. Photocycloaddition of the cyclohexenone derivative 4141, as a 3 2 mixture of anti- and, vv -diastereomers at — 70 C, resulted in quantitative cycloaddition of the anti-diastereomer to yield the cis decalin system 5. The syn-diastereomer gave three minor photoproducts which were not characterized. 

The allene functionality is also useful in radical cyclizations. Radical precursor 867 (R=OH OAc SePh) is readily cyclized to a 5 1 mixture of 868 and 862 together with two other cyclic compounds. After separation of the desired product 868, the methyl group is oxidized to an alcohol and then acetylated. Finally, the carbonyl groups are reduced to give ( + )-heliotridine (850) [191]. 

If one investigates the effect of isoelectronic substitution within the allenic functionality (allene ketene imine ketene), one considers structural units that are equivalent concerning the number of heavy atoms, the linear arrangement of the heavy atoms, and the total number of electrons for these molecules or correspondingly substituted molecules. The relevant (nongeometrical)... 

Craft and Gung have disclosed the first transannular (4-1-3) cycloaddition of a symmetrical substrate using an allene function catalyzed by Pd(ll) in reaction with a furan group. The substrate itself is produced by a Grubbs I RCM, and the nonsymmetrical product should be a useful intermediate for the cortistatins (Scheme 33) [70]. 

Allenic acids, containing the —CH=C=CH— system, occur only rarely in lipids but the known examples are of interest because the glycerides are optically active by virtue of the allene function. Allenic acids are isomeric with acetylenic compounds and each can be rearranged to the other. 

Kanematsu and coworkers developed the intramolecular allene+diene Diels-Alder cycloaddition into a new indole synthesis (Scheme 24, equations 1, 2) [118-121], The allene functionality in 67 was prepared by homologation (HCHO, CuBr, i-Pr NH). This cycloaddition strategy was successfully applied to syntheses of hippadine (equation 2) [119], and ( )- and (+)-d5 -trikentrin B [120, 121],... 

Gem-dihalocyclopropanes are important starting materials in organic synthesis, especially for the preparation of monohalocyclopropanes, cyclopropanes, allenes, functionalized cyclopropanes, cyclopropenes, etc. (for reviews see Refs. (55-57). 

This switch was rationalized by an increased steric bulk in the transition state after the initial allene functionalization with the hypervalent iodine reagent. 

Syntheses of the allene functional group have been included in a recent volume. Acetylene- and allene-containing animal alkaloids have been reviewed. ... 

This description is too simple. If 6 is the target then the precursor would be 7, which is an impossible solution due to the allenic function in a five-membered ring (equation 9) ... 

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