Allene derivatives

Trimethylsilylation with trimethylchlorosilane affords the corresponding allene derivative, hydroxyalkylation with aldehydes and ketones gives mixtures of comparable amounts of acetylenic and allenic carbinols. 

We presume that the dilithiopropyne causes partial isomerization into the allenic derivative. The treatment with KOH is to complete this transformation. When the latter treatment was not carried out, considerable amounts of the acetylenic diacids were sometimes found in the crude product. 

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

As typical examples of crystal-to-crystal thermal reactions, the cyclization of allene derivatives to four-membered ring compounds and the transformation of a racemic complex into a conglomerate complex are described. 

Crystal-to-Crystal Cyclization Reactions of Allene Derivatives... 

The usefulness of allene derivatives has also been revealed in other examples. Thus, the annulated tetrasubstituted furan illustrated in the following scheme was delivered in a moderate yield using the diazoallene as precursor by a two-step reaction in the presence of Rh-catalyst <06S3605>. 

Allenyl cations have been generated by solvolysis of allenic derivatives, by photolysis of allenyl halides and by reaction of metal salts with allenyl and propargyl halides. This review will delineate these reactions. The related butatrienyl cations are not many and they will be only briefly described. 

An interesting annelation reaction of allene-derived 13-dipoles with 3-(IV-aryliminomethyl)chromones 38 affords, in fair yields, after [4 +3] cycloaddition and a subsequent cascade of rearrangements, derivatives of the novel iV-aryl-2,3-dihydro-4-ethoxycarbonylchromano[2,3-h]azepin-6-one system 39 (for example, R = Me, R1 = Cl) (Scheme 9). In the initial cycloaddition, the substituted chromone acts as an azadiene moiety <00OL2023>... 

The lactam 145, bearing a terminal triple bond, is transformed into the corresponding allene derivative 146 through a Crabbe reaction (Equation 7). Using Pd(PPh ()4 as the catalyst and in the presence of phenyl iodide, the corresponding indolizine is obtained. The lactam nitrogen atom is added to the central carbon atom of the allene... 

The 1,4-addition of an appropriate reagent, such as a hydrosilane or a hydroborane, to a conjugated enyne produces an allenic derivative. Occasionally, 1,2-addition to the alkynyl moiety of the substrate competes as an undesirable side reaction to give a conjugated diene (Scheme 3.66). Suppression of the latter reaction path is required for the selective preparation of the allenic products. 

The synthesis of chiral liquid-crystalline allenes was reported by Tschierske and co-workers (Scheme 4.10) [14]. An asymmetric reduction of 41 with Alpine borane was a key step to an enantioenriched allene 44. After removal of the silyl group, the allenic alcohol was etherified by the Mitsunobu method to give 45, the first liquid-crystalline allene derivatives. 

To prepare the other cross-conjugated allene, 4-methylene-l,2,5-hexatriene ( 2-allenyl-1,3-butadiene ) (23), the allene alcohol 215 was first converted into the phosphate 216, that readily underwent an SN2 -type substitution with allenylmagnesium bromide to yield the target hydrocarbon as a highly reactive allene derivative (Scheme 5.32) [76],... 

Less common addition reactions such as the bromination of trifhioromethyl-substi-tuted butatrienes [30] or the reaction of tetrafluoroallene with boron trifluoride have also been reported [283]. Especially the interaction of phosphorylated allenes with electrophiles was summarized in a review by Alabugin and Brel [8], whereas Smadja [284] published a more general overview about the electrophilic addition to allenic derivatives. 

Donor- and acceptor-substituted allenes with general structures 1 or 2 (Scheme 8.1) have the most obvious synthetic potential among functionalized allene derivatives and therefore they serve as versatile building blocks in many synthetic endeavors [1], As expected, the reactivity of the double bonds of 1 or 2, which are directly connected to the activating substituents, are strongly influenced by these groups. Hence there is enol ether or enamine reactivity of 1 and Michael acceptor type chemistry of 2. In addition, the terminal double bonds are also influenced by these functional groups. 

In this chapter we shall deal with donor-substituted allenes of type 3, 4, 5 and 6 (Scheme 8.2), among which oxygen-substituted allene derivatives 3 are of major importance. They have been utilized for numerous syntheses of interestingly func-... 

This chapter focuses on cycloaddition reactions in which at least two new cr-bonds are formed between allene derivatives and other unsaturated organic molecules. Intramole-cular cycloaddition reactions are also described. The reactions are categorized according to assembly modes, such as [m + n]-cycloaddition, where the variables m and n simply denote the number of atoms that each component contributes to the ring construction. Some electrocyclic reactions of allene derivatives are also included. 

A large number of reaction conditions have been defined for the rearrangement of various allene derivatives into small heterocycles. The rearrangements have been accomplished variously with acids, bases or oxidatively. 

In addition to a-allenic a-amino acids, the corresponding allenic derivatives of y-aminobutyric acid (GABA) have also been synthesized as potential inhibitors of the pyridoxal phosphate-dependent enzyme GABA-aminotransferase (Scheme 18.49) [131,138-142]. The synthesis of y-allenyl-GABA (152) and its methylated derivatives was accomplished through Crabbe reaction [131], aza-Cope rearrangement [138] and lactam allenylation [139], whereas the fluoroallene 153 was prepared by SN2 -reduc-tion of a propargylic chloride [141]. 

Scheme 18.49 Allenic derivatives ofy-aminobutyric acid (GABA).

The protected propargylamines 224 (R = H, CH2C02Me or CH2CH2C02Me) react with aqueous formaldehyde under copper bromide catalysis to yield the allene derivatives 225. Deprotection with ethereal hydrogen chloride affords the free amines218. 

Investigations of base-catalyzed isomerizations of allene derivatives have been recently continued. For instance, the rearrangement of allene ethers 53 under superbasic conditions (KOH-DMSO) is considered as one of the steps in hydration of acetylene derivatives (equation 17)31,32. 

Hydroxycoumarins are alkylated under extremely mild basic liquiddiquid phase-transfer catalytic conditions to produce the ethers and 4-alkylated derivatives 141 ]. The major product tends to be the ether (50-60%) but the yield of the C-alkyl-ated product is significant with allyl bromide and with propargyl bromide, where rearrangement of the allenic derivative occurs. 

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%). 

As with the reaction of pyrroles, diazoles and triazoles react with propargyl bromide to yield TV-substituted products and, depending upon the base strength, either TV-prop-2-ynylazoles or allenic derivatives are formed [30]. Generally, with potassium carbonate under soliddiquid two-phase conditions at room temperature in the absence of a solvent, the prop-2-ynyl compounds are formed as sole products, whereas with solid potassium hydroxide at elevated temperatures the allenes are obtained as the major products. Benztriazole produces a mixture of the N1- and N2-prop-2-ynyl, and N2-allenic derivatives, whereas with potassium hydroxide only the N -allenic derivative is obtained. The alkynes readily isomerize to the allenes in the presence of base and the quaternary ammonium salt, or upon treatment with methanolic sodium hydroxide. A series of l-(alk-2-ynyl)imidazoles have been prepared, as intermediates in the synthesis of imidazopyridines [31 ] and the reaction of 3-hydroxymethylpyrazoles with propargyl bromide leads to pyrazolooxazines [32]. 

If doubly-bonded compounds >M = X (M = Si, Ge, Sn) are now well known, this is not yet the case for the heavy allenic derivatives >M = C = X. Transient silaallenes >Si = C = C 160-167 or silaazaallene >Si = C = N—168 were postulated some years ago, but the first stable derivative of this type, a formal 3-stanna-l-azaallene >Sn = C = N —, was isolated only in 1992 by Griitzmacher et al169 The compound Tbt(Mes)Si = C = NR170 has also been obtained, but according to the authors it is closer to a silylene Lewis base complex than to a silacumulene. The first stable silaallene was only reported in 1993 by West et al.111 and the first metastable >Si = C = P— was characterized still more recently.172... 

Recent advances in the rhodium-catalyzed [4-1-2] reactions have led to the development of the first highly regioselective intermolecular cyclization, providing access to new classes of carbocycles with both activated and unactivated substrates. The chemo- and stereoselective carbocyclizations of tethered diene-allene derivatives afford new classes of 5,6- and 6,6-bicyclic systems. Additionally, examination of a wide range of factors that influence both diastereo- and enantioselectivity has provided a significant advance in the understanding of catalyst requirements across these systems. 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

Similarly, the allenic derivatives 120 and 121 have been obtained from propargylic alcohols as shown in Scheme 7.34. °... 

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