Propargylation anilines

TRANSITION METAL-CATALYSED CYCLIZATION OF A/-ALLYL-AND /V-PROPARGYL ANILINES... 

HCA478). A similar route to quinolines via 1,2- dihydroquinolines starts fromN-propargyl-anilines and is copper catalyzed (62JOC4713). The allyl ether of cyclohexanone oxime (126) heated in benzene at 200 °C gives 5,6,7,8-tetrahydroquinoline (79S221) the proposed mechanism is reinforced by the isolation of a compound (128) formed from the ether (126) and a suggested intermediate (127). 

Intramolecular cyclization of fV-propargyl anilines in the presence of IC1 yields the dihydroquinoline, which is easily transformed into the fully saturated quinoline in high yield (Scheme 25) <20050L763>. This process was intentionally developed as a facile route to a variety of substituted quinolines. The use of iV-propargyl anilines in the presence of cuprous chloride yields the dihydroquinoline (Equation 55) <1995TL7721>. 

PdCl2(Ph3P)2, TEA, DME, H2O, 2-3 h, 45-78% yield. Propargyl anilines are cleaved similarly hut in generally low yields. ... 

An electrophilic cyclization of 7V-(2-alkynyl)anilines was developed that allow the synthesis of a variety of substituted quinolines 115. Illustrated in Scheme 32 the cyclization of the propargylic aniline 116 by ICl afforded 117, which then could be converted to 115 under basic conditions. 

In this method the initial iodocyolization of a variety of propargylic anilines can be accomplished and followed by palladium-catalyzed substitution reactions to provide further elaboration of the... 

Several metals have been reported of being able to hydroaiylate alkynes as in the examples shown below. Thus, di-substituted-propargyl anilines can be cyclized either in the presence of copper(I) chloride at reflux or by a mixture of palladium acetate and trifluoroacetic acid. ... 

More recently, Saito and Hanzawa demonstrated that a variety of fused, tri-, tetra-and penta-substituted indoles 190 could be efficiently accessed via the Rh(I)-catalyzed cydoisomerization of N-propargyl anilines 188 (Scheme 9.68) [225, 226]. This transformation presumably involves the initial Rh(I)-catalyzed amino-Claisen rearrangement of 188 to produce a putative reactive allenyl aniline intermediate 189, which is smoothly converted into the indole core, as exemplified by the cycloisomerization of an independently prepared allene 191 (Scheme 9.69). On the other hand, the latter transformation of allenes can be achieved under thermal reaction conditions, albeit with a diminished effidency. 

Saito and Hanzawa extended their cydoisomerization route, involving the amino-Claisen rearrangement-cyclization cascade reaction (Scheme 9.68), to a one-pot procedure toward the functionalized 2,3-dimethylindole derivatives 281 (Scheme 9.97) [226]. The key propargyl anilines 280 were generated in situ via the propargylation of substituted anilines 278 with the propargrl bromide 279. 

Saito and Hanzawa have reported a cationic rhodium(I)-catalyzed aza-Claisen rearrangement of 7V-propargyl aniline 380. The un-catalyzed thermal variant required extremely high reaction temperatures and produced poor conversions. The mild protocol is an efficient entry for the synthesis of various indole derivatives. The reaction proceeds through the o-allenylaniline intermediate 381 and a subsequent cyclization results in 382. ... 

N-propargyl-anilines and coumarins were efficiently transformed into the corresponding quinolines catalyzed by gold NPs supported on Ti02 and AI2O3 under mild conditions [86]. In all cases, pyridocoumarins and quinolines were obtained in high yields, via a synthetically useful procedure (Scheme 5.35). 

Cyclizations of alkynyl derivatives proved to be a synthetically convenient way to 2-(trifluoromethyl)quinolines. Indeed, the intramolecular cyclization of N-(a-trifluoromethyl)propargyl anilines 89 takes place with the gold(I) catalyst under extremely mild conditions to afford 2-trifluoromethylquinolines 90 (Scheme 36). The reaction mechanism has been suggested to involve cyclization and oxidation steps [57],... 

Saito et al. demonstrated that the reaction of A-propargyl anilines 142 in the presence of cationic rhodium catalysts produced substituted indoles 143 in good to excellent yields (Scheme 27.47) [60]. Mechanistic studies revealed that the reaction proceeds via amino-Claisen rearrangement and subsequent cyclization of resulting A-allenylaniline intermediate 144. 

Propargyl alcohol is available from the General Aniline and Film Corporation, Easton, Pennsylvania. 

Reaction of the chloro-substituted propargyl acetate 132 with aniline gave the pyrrolidine derivative 133 that was cyclized through treatment with... 

Examples of the formation of sulphur containing heterocycles by similar transformations are quite rare. The palladium catalysed ring closure of S-propargyl-2-iodophenylmercaptane in the presence of formic acid and an amine-base, analogously to phenols and anilines, led to the formation of the partially reduced benzothiophene skeleton, bearing a 3-methylydene function (3.32.),40... 

Fig. 12. Reaction of monoalkyl monohydrogen phthalate with aniline. [Ester] = [Amine] = 0.25 M, T = 70 °C, Solvent = DMSO-d6. ( ) trifluoroethyl ester ( ) 1,3-dichloroisopropyl ester ( ) ethylglycolyl ester (A) propargyl ester (T) methyl ester...

Nitrogen nucleophiles also react smoothly. The reaction of optically active propargyl mesylate 198 with aniline without a catalyst gives 200 with inversion. However, the Pd-catalysed reaction affords 199 with retention of stereochemistry [44], The 4-ethenylidene-2-oxazolidinone 202 is obtained by intramolecular reaction of the biscarbamate of the 2-butyn-l,4-diol 201 [45],... 

Above a critical volume it can be shocked into detonation. Mixtures with 3-bromopropyne are shock- and heat-sensitive explosives. Violent reaction with aniline + heat, alcoholic sodium hydroxide, sodium methoxide, and propargyl bromide. When heated to decomposition it emits very toxic fumes of Cr and NO. ... 

Reaction of propargylic mesylate 233 with aniline proceeded without a catalyst to afford the propargylamine 235 with inversion of configuration (Scheme 11-60). On the other hand, the palladium-catalyzed reaction of 233 gave 234 with retention of configuration [53]. 

Reaction of l-chloro-l,3,3-triphenylallene (19) with p-toluidine in the presence of silver triflate gave 2,3,4-triphenylbuta- l-aza-1,3-diene derivative 22a via a novel l, 2-phenyl shift not reported earlier in the solvolysis of allenyl chlorides. The reaction takes place via the formation of the allenyl cation, which is captured as its canonical propargyl cation, first affording the protonated amine 20 (R = Me). Proton transfer from the nitrogen to the acetylenic carbon is followed by migration of a phenyl group in the intermediate vinyl cation 21 (R = Me) to afford the iminium triflate 22a. The latter is hydrolyzed by aqueous sodium hydroxide to the azabutadiene 23 (equation 5). Similar reaction of 19 with aniline and silver triflate afforded the corresponding iminium triflate 22b. ... 

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