Allenyl amine

Propynyl dialkylamines are produced in low yields (see Table II) when the stoichiometric amount of reagents are used. When an excess of lithium dialkyl-amide is used, partial isomerization of the product to allenyl amines, CH2=C=CHNR2 [13], takes place. 

Ibuka et al. observed that under the catalysis of Pd(PPh3)4 (4-20 mol%), optically active 2,3-allenyl amines 20 can be cyclized in the presence of aryl halides in DMF (Scheme 8). The chirality of the allene moiety was smoothly transferred into the final products, i.e., 2,5-dihydropyrrole [8]. 

The reaction of the a-methyl-substituted allenylamine 23 afforded the trans product with a de ratio of 94/6 (Scheme 11). 3,4-Allenyl amines 24 underwent the same transformation in DMF to afford the four-membered-ring czs-alkenyl azetidines 25 (Scheme 12). The reaction of 24 with R =o-Ns in DMF or R =Mts in dioxane afforded the same products with relatively low stereoselectivity. Formation of a 7i-allylpalladium intermediate and cyclic allylic substitution was proposed for this reaction (pathway 1, Scheme 1). 

In 1999, Hiemstra et al. demonstrated that the Pd(PPh3)4-catalyzed reaction of l-methoxycarbonyl-3,4-allenyl amines 26 with aryl iodides (triflates) or... 

Phenyl-methyl-allenyl-amine (N, N-methyl-phenyl-aminoallene)... 

Grigg and co-workers have used a sequential, one-pot Petasis borono-Mannich reaction with either Pd(0)-catalyzed carbonylative amination cyclization or Pd(0)-cat-alyzed allenylation/amination cyclization (Scheme 7.7) [46]. The overall approach results in the formation of a-amino acid derivatives of isoindolone 25 and 4-methylene-3,4 -dihydroisoquinoline 26. While this is the only reported example of a combination of a Petasis borono-Mannich reaction with a Pd(0)using other Pd(0) or transition metal catalyzed reactions is a very attractive strategy for the synthesis of complex molecules or combinatorial libraries. 

Reactions with in situ Generated Iminium and a-Acyl Iminium lons These reactions allow the preparation of a-allenyl amines and amides (eqs 21 and 22). The photoinduced addition reaction leads to a mixture of two products (eq 23) ... 

Several groups also used NHC-Ag catalysis in order to promote the reaction of a terminal alkyne with an electrophile. Following this process, Sono-gashira couplings and the addition of alkynes to isatins or C02 were described. In the last case, supported NHC-Ag nanoparticles were used. The efficiency of the process was attributed to both the activation of the alkyne by the NHC-Ag complex and the activation of CO2 by a free NHC moiety in a cooperative manner. CO2 insertion has also been exploited in order to synthesize cyclic carbonates and carbamates by NHC-Ag catalysis starting from epoxides, propargyl alcohols or allenyl amines [eqn (11.4)]. ... 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

McDowell and Stirling194 studied electronic effects upon the reactivity of aryl vinyl sulfones towards amines. Rate constants for t-butylamine addition in ethanol at 25 °C were well correlated by the Hammett equation, with p = 1.59. Comparison of this with p values for H-D exchange mentioned above191 suggested considerable carbanionic character in the transition state, perhaps in a concerted mechanism. Rates of addition of amines to alkenyl, allenyl and alkynyl p-tolyl sulfones have also been measured195. 

Recently, the solvolyses of l-chloro-l,3,3-triarylallenes 10 (andof 1-butyl-3,3-diphenyl-allenyl chloride) were carried out in the presence of thiocyanate and o-ethyl dithiocar-bonate anions as nucleophiles and found to give the corresponding allenyl derivatives 11 and 12 in good yield (equation 3)18. However, when potassium cyanate was used as a nucleophile, the cyanate ion attacked at the /-position to give the propargyl amines 14 after decarboxylation of the unstable intermediate 13 (equation 4). 

The competition between a propargylic ether and a teriary propargyhc amine provided an allenyl ether rather than an allenylamine [182], The reaction was also successful with propargyl allyl ethers [232]. An additional ester group in the propargylic position is tolerated [233], and consequently the reaction also works with esters of propargyhc alcohols [234—236]. In the past 4years, several derivatives of carbohydrates were converted successfully [217, 237-241] two examples are the isomeriza-tions of enantiomerically pure 98 [242] and 100 [217, 243] (Scheme 1.43). 

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

One of the rare applications of selenium-substituted allenes was recently reported by Ma et al. [182]. The allenyl selenide 352 undergoes an iodohydroxylation or iodo-amination, depending on the amount of water used, leading to the formation of allyl alcohol 353 and allylacetamide 354 (Scheme 8.97). When the reaction is performed with 12-16 equiv. of water, allyl alcohol 353 is exclusively formed, whereas the use of 1 equiv. of water exclusively provides the amide 354 in 64% yield. 

A tertiary homopropargylic alcohol could also be prepared by treatment of ethyl acetate with two equivalents of B-allenyl-9-BBN. However, the reaction proceeded slowly and was not general for other esters, which proved to be unreactive, as were tertiary amides and alkyl halides. However, homopropargylic amines could be prepared in high yield and with minimal allenic byproduct through allenylboration of imines with B-allenyl-9-BBN (Eq. 9.24). 

Allenyltrichlorosilanes can also be prepared by Sn2 displacement of propargylic chlorides with a Cu or Ni complex of HSiCl3 [56]. The reaction requires an amine base and a donor solvent such as THF or propionitrile (Table 9.32). Conditions can be adjusted to favor the propargylic or allenic silane, which is not isolated, but treated directly with various aldehydes to afford allenylcarbinols (A) or homopropargylic alcohols (B). These reactions presumably proceed by an SE2 pathway, such that the allenyl products arise from the propargylic silane and vice versa. 

Allenyl bromide accepts the nucleophilic attack of amines or potassium thio-acetate leading to propargylic amines or thioesters via the alkenylidenecarbene 132 or zwitterion intermediate 133 [66],... 

The intramolecular dipolar cycloaddition of a nitrone with an unactivated allene was also studied [76], Treatment of 5,6-heptadien-2-one with N-methylhydroxyl-amine in refluxing ethanol yielded allenyl nitrone 78, which cyclized with the terminal allenic C=C bond to give an unsaturated bicyclic isoxazolidine. On the other hand, the site selectivity decreased with an allenic ketone having a trimethylene tether. 

Most of the substrates for these isomerizations have a tetrahedral carbon with at least one hydrogen substituent between the carbonyl group and the alkyne. Due to the comparable high acidity of this C-H bond neighboring the carbonyl group, already a weak base such as a carbonate, a tertiary amine or aluminum oxide can deprotonate this position and a subsequent protonation at the other end of the pro-pargyl/allenyl anion delivers the allene. 

A related amination/rearrangement/cyclization tandem sequence had been introduced by Cossy [49]. Starting from cyclic epoxyketones 224 the reaction with propargylamines 225 caused an oxirane-opening condensation process to generate the enaminoketones 226. Upon heating in toluene to reflux, aza-Claisen rearrangement delivered the intermediate allenyl imines 227, which... 

In contrast to ruthenium and osmium, the reactivity of iron allenylidenes remains almost unexplored. Only the behavior of the cationic diphenylallenylidene-Fe(II) derivative frans-[FeBr(=C=C=CPh2)(depe)2]" has been studied in detail. Thus, it has been found that this complex reacts exclusively at Cy with both neutral (amines, phosphines) and anionic (H , MeO , CN ) nucleophiles [105-107]. This behavior contrasts with that of the neutral Fe(0) derivative [Fe =C=C=C(f-Bu)2 (CO)5] which undergoes PPhs-attack at Co- to afford the zwitterionic phosphonio-allenyl species [Fe C(PPh3)=C=C(f-Bu)2 (CO)5] [104]. 

---