Esters propargylic

Propargylic (or 2-alkynyl) compounds are derivatives of alkynes. However, Pd-catalyzed reactions of propargylic derivatives, particularly esters and halides, are very different mechanistically from those of simple alkynes, except in a few cases. Therefore, the reactions of propargylic esters and halides are treated in this section separately from those of other alkynes. However, some reactions of propargylic alcohols, which behave similarly to simple alkynes, are treated in Section 6. 

Prop-2-ynyl (Propargyl) Ester HC=CCH202CR Cleavage... 

FIGURE 7.7 Effect of the allosteric modulator ebumamonine on the potency of muscarinic agonists on m2 receptors. It can be seen that while no change in potency is observed for APE (arecaidine propargyl ester) pilocarpine is antagonized and arecoline is potentiated, illustrating the probe dependence of allosterism. From [1],... 

Reaction between propargyl esters and organometallic reagents... 

C2()H29NOi 94868-25-4) see Oxypyrronium bromide a-cyclohexylphenylglycolic acid propargyl ester (C12H20O3 81039-74-9) see Oxybutynin [(4-cyclohexylphenyl)methylene]propanedioic acid diethyl ester... 

Correa, A., Marion, N., Fensterbank, L., Malacria, M., Nolan, S.P. and Cavallo, L. (2008) Golden Carousel in Catalysis The Cationic Gold/Propargylic Ester Cycle. Angewandte Chemie International Edition, 47, 718-721. 

Rearrangement of acetylenic sulphenates to the allenic sulphoxides 151 was discovered when the synthesis of propargylic ester of trichloromethanesulphenic acid 152 was attempted (equation 86). This reaction is of general scope and gives very good yields of allenic sulphoxides (Table 14) from structurally diverse cohols and various sulphenyl chlorides Reaction of alkynols 153 with benzenesulphenyl chloride in the presence... 

The Pd°-catalyzed transformation of enediynes represents a highly efficient and effective approach for the synthesis of polycyclic compounds, with different ring sizes being obtained by a variation of the tether [129]. In this respect, reaction of 6/1-270 led to the tricyclic product 6/1-271 as a single diastereomer. The initial step is a chemoselective hydropalladation of the propargylic ester moiety in 6/1-270 to give an alkenyl-Pd-species, according to the mechanism depicted in Scheme 6.71. A hexatriene is formed as a byproduct. 

Azomethine ylides of pyrrolo[l,2- ]pyrazine <1996JOC4655> and 3,4-dihydro pyrrolo[l,2-tf]pyrazine <1997T9341> undergo 1,3-dipolar cycloadditions with a number of dipolarophiles. For example, the ylide 178 reacts with propargylic ester 179 to give the tricyclic derivative 180 (Equation 43). 

To facilitate parallel synthesis and purification of triazolyl derivatives of sugars, the products are tagged with an azulene chromophore. For this purpose, guajazulene, an inexpensive azulene, is converted to propargylic ester 1094 and reacted with mannose derivative 1095 to provide a mixture of regioisomers 1096 (44%) and 1097 (32%). Separation of the products can be easily achieved by chromatography because they are visible on the column (Scheme 181) <2006EJ01103>. 

Table 4 1,3-Dipolar cycloaddition of propargyl esters 86 to sydnone 85 (Scheme 3) <2006H1007, 2006SL901 >...

The ortfe-directed lithiation protocol allows selective functionalization of 3-arylsydnones in the aryl ring, the C4 position of the sydnone ring, or both simultaneously. The method allows access to fused ring structures (Sections 5.03.5.2.4 and 5.03.7.1.1). Reliable routes to otherwise unknown oxadiazolidines have been established (Section 5.03.9.4). Regiospecificity can now be achieved by judicious choice of substituents when propargylic esters react with sydnones to form pyrazoles (Section 5.03.5.2.6). 

The ester/alkyne rearrangement system can be extended by conjugation to involve a more distant site. The reaction of diethyl phosphorochloridate with 3-methylhex-4-yne-2-ene-l-ol leads to the vinylogous propargylic ester rearrangement as shown in Equation 4.39.176... 

A last and unusual substrate in this section is a propargyl ester of a phosphorus acid diamide 104 [247] (Scheme 1.45). 

Two different types of substrates are used here, propargyl sulfenates and propargyl sulfmates. In both cases often the propargylic esters are prepared and then converted to the allenes in situ. 

Often these intermediates are generated in situ from orthoesters and propargylic alcohols [551] or propargyl esters such as 167 (Scheme 1.74) [552],... 

In analogy with the propargyl esters, propargyl acetimidates can be used, and then the equilibrium clearly lies on the side of the allene [574, 575]. Often the acetimidate is a substructure of a heterocycle such as 171 (Scheme 1.76) [576] or related compounds [577, 578]. 

Scheme 4.3 Organocopper-mediated stereospecific substitution of propargyl esters.

An alternative, but related, route to allenic titanium reagents from propargylic esters has been reported recently. Reaction of titanocene dichloride with BuMgCl and Mg yields a reactive titanocene intermediate, formulated as Cp2Ti. This reduced Ti species reacts in situ by oxidative addition to propargylic acetates. The allenyltitanium reagents thus produced add to aldehydes and ketones, as expected, to afford homopropargylic alcohols (Table 9.27) [43]. 

The first syntheses of a-allenic a-amino acids [131,133] took advantage of Steg-lich s [134] protocol for the oxazole-Claisen rearrangement of unsaturated N-ben-zoylamino acid esters (Scheme 18.46). Thus, treatment of the propargylic ester 143 with triphenylphosphine and tetrachlormethane furnished the allenic oxazolone 144, which was converted into the amino acid derivative 145 by methanolysis. Stepwise deprotection finally led to the allenic DOPA analog 146, which shows a much higher decarboxylase-inhibiting activity than a-vinyl- and a-ethynyl-DOPA [133],... 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

Wolf-Pflugmann M, Lambrecht G, Wess J, Mutschler E. (1989). Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester. Arzneimittelforschung. 39(5) 539-44. 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

Oxybutynin Oxybutynin, 4-diethylamino-2-butynylic ester a-phenylclohexaneglycolic acid (14.1.35), is synthesized either by a Mannich reaction using propargyl ester of a-phenyl-a-cyclohexaneglycoUc acid, paraform and diethylamine, or transesterification of the methyl ester of a-phenyl-a-cyclohexaneglycolic acid using l-acetoxy-4-diethylamino-2-butene in the presence of sodium methoxide [26]. 

In a similar way, propargyl esters of A -benzoyl-a-amino acids have been converted into a-allenyl-a-amino acid esters 113 by cyclization to oxazoles 111 followed by Claisen rearrangement to the 4-allenyl-2-phenyl-5(4//)-oxazolones 112. Oxazolone ring opening with methanol then afforded 113 (Scheme 7.32). ... 

The other strategy requires dienes or enynes containing allylic or propargylic ester fragments. The main pathway in this case involves the formation of allylpalladium intermediates, which perform carbapalladation of double or triple bonds with subsequent acylpalladation forming two cycles, and termination by palladium hydride elimination or other usual trapping pathways (Scheme for example, in the following examples in Scheme 22. ... 

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...

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