Alkynyl benzoates

Alkynyl carboxylates, RC=C02CR. A wide variety of these previously unknown esters can be prepared in a two-step procedure from 1, as formulated for the alkynyl benzoates (2).3... 

Electrophilic cyclization of ortho-alkynyl benzoates using iodine or IC1 affords 4-iodocoumarins in good yield (Scheme 206) <2002TL7401, 2002T5023, 2003JOC5936>. Electrophiles other than iodine can effectively mediate the electrophilic cyclization of ortho-alkynyl benzoates with concomitant incorporation of the electrophile into C-4 of the resulting isocoumarin (Equation 324) <2003JOC5936>. 

The conversion of alkynyl(phenyl)iodonium ions to alkynyl esters with carboxylate ions via the MC mechanism (equation 45) has been proposed81. Evidence for the viability of this process is provided by the generation of 3,3-dimethyl-1-cyclopentenyl benzoate in addition to the expected alkynyl benzoate when the iodonium triflate shown in equation 90 is mixed with sodium benzoate in dichloromethane (yields not reported)3. 

Iodocyclisation of 2-(l-alkynyl)benzoates under mild conditions leads to 3-substituted 4-iodoisocoumarins. Application of the method to (Z)-2-alken-4-ynoates gives 6-substituted... 

Various electrophiles bring about the cyclisation of o-(l-alkynyl)benzoates and (Z)-2-alken-4-ynoates to isocoumarins and pyran-2-ones in high yields extension to the synthesis of bis-coumarins and hetero-fused pyranones is successful (Scheme 25) <03JOC5936>. 3-Aryl-4-iodoisocoumarins, prepared in a similar manner, undergo Stille reactions and can readily be deiodinated <03T2067>. 

A second type is the reaction of alkynylphenyliodonium tosylates with benzoate loaded ion exchange resin. Alkynyl benzoates (86) and phenyl iodide were the products which could result from ligand coupling on the intermediate alkynylphenyliodonium benzoates. However, isolation of these intermediates has not been possible. 1 6 (Scheme 5.8) The same reaction with diethyl phospHate led to the corresponding phosphate esters (87). 1 5,197... 

Reaction of trimethylsilylalkynes with 16 in dichloromethane in the presence of BF3 OEt2 at room temperature followed by heating in methanol at 60 °C results in the stable heterocyclic alkynyliodonium salts 17 [Eq. (9)] [31]. These species represent intramolecular iodonium salts where the counterion is a carboxylate. Unlike the acyclic alkynyl(phenyl)iodonium carbox-ylates 18, that are unstable to isolation and decompose to the corresponding alkynyl benzoates 19 [Eq. (10)] [32], the cyclic analogs 17 are readily isolable. 

In contrast, alkynyl dialkyl phosphate esters, 78, are formed in good isolated yields by either the treatment of alkynyliodonium triflates with (R0)2P02Na or the reaction of terminal alkynes with [hydroxy(phosphoryloxy)iodo]benzene, 77 [Eq. (34)], or the sequential treatment of alkynylsilanes with PhIO Et20Bp3 followed by aqueous (R0)2P02Na [Eq. (35)) [61]. These new, alkynyliodonium-derived, acetylenic esters have potent biological activity [4] in particular, the alkynyl benzoates are protease inhibitors [62], whereas the alkynyl dialkylphos-phates, 78, are inhibitors of a bacterial phosphotriesterase [63]. 

Pure alkynyl esters 94-96 are colorless or pale yellow liquids or solids with a low melting point. Most of them are relatively stable and can be stored in a refrigerator for extended periods. Of the three classes of alkynyl esters the sulfonates 94 are the most thermally stable some of them may even be distilled in vacuum at temperatures of 100-130 The carboxylate esters 96 are the least stable, in fact, so far only alkynyl benzoates (96, R = Ar) and pivalates (96, R = -Bu) have been isolated in pure form. Alkynyl esters of such acids as formic and acetic are too unstable to isolate k All three classes of alkynyl esters and, especially, carboxylates are water sensitive and rapidly decompose by hydrolysis in the presence of moisture. 

The mechanism of the neutral reaction is more unusual, and was investigated in detail for alkynyl benzoates. Neutral hydrolysis of propynyl benzoate (116) in aqueous acetonitrile leads to keto-ester 124 in 46% yield along with the expected propanoic and benzoic acids. The mechanism of this reaction involves an unusual cyclization pathway including the intermediate formation of dioxalene 123 (equation 76). This mechanism was unveiled by labeling studies in H2 as well as careful NMR studies. Further evidence for this mechanism comes from the isolation and characterization dioxalenes 125 from the reaction of alkynyl benzoates with anhydrous methanol (equation 77). ... 

Other pseudo-halides are used for carbonylation. Phenyl tluorosulfonate (484) can be carbonylated to give benzoate[337]. Aryl(aryl)iodonium salts[338], aryl(alkenyl)iodonium salts (485)[339], and arylialkynyl)iodonium salts (486)[340] are reactive compounds and undergo carbonylation under mild conditions (room temperature, 1 atm) to give aryl, alkenyl, and alkynyl esters. lodoxybenzene (487) is carbonylated under mild conditions in... 

Liquid crystals based on aliphatic isocyanides and aromatic alkynyls (compounds 16) show enantiotropic nematic phases between 110 and 160 °C. Important reductions in the transition temperatures, mainly in clearing points (<100 °C), areobtained when a branched octyl isocyanide is used. The nematic phase stability is also reduced and the complexes are thermally more stable than derivatives of aliphatic alkynes. Other structural variations such as the introduction of a lateral chlorine atom on one ring of the phenyl benzoate moiety or the use of a branched terminal alkyl chain produce a decrease of the transition temperatures enhancing the formation of enantiotropic nematic phases without decomposition. 

Hoppe and Gonschorrek also reported the interesting formation of an enyne structure [137]. Deprotonation of allenyl carbamates 242 bearing a benzoyloxy group caused a 1,4-elimination of lithium benzoate, furnishing 1-alkynyl carbamates 243 in moderate to good yield (Scheme 8.63). 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

Alkynyl carboxylate esters, 75, are obtained in the reaction of lithium acetylides with bis(acyloxy)iodobenzene, 73 [Eq. (32)] [59], These reactions are likely to proceed through the intermediacy of the respective alkynyliodonium carboxylates (74), although no such salts have been isolated to date as they spontaneously decompose, via loss of iodobenzene, to the alkynyl carboxylates, 75. Only benzoate esters (75 R = CgHj) are sufficiently stable to isolate and store pure for longer periods. Simple alkylcarboxylates such as acetates are not stable although the hindered pivaloate ester (65 R = t-Bu, R = t-Bu) has been isolated in low yield [59]. Among the reasons for the instability of these esters is their sensitivity to moisture they both readily add water and undergo subsequent hydrolyses [60]. Because of the sensitivity to moisture, the isolated yield [41] of bisalkynyl benzoates, 76, from the bisalkynyliodonium triflates, 35, is only 6-15% [Eq. (33)]. 

Alkynyl(phenyl)iodonium carboxylates 99 are even less stable than phosphates 98 and decompose immediately upon generation from iodonium triflates 100 or benzoate 101 with the formation of the desired alkynyl carboxylates 96 (equation 65) k... 

X-ray structural data have been reported for three alkynyl esters ethynyl benzoate 113, propynyl / -nitrobenzoate 114 and propynyl tosylate 115. 

Analogously to siloxy- and alkoxyacetylenes (see Sections II.D.2 and III.C.4), alkynyl esters are good partners in [2+2] cycloaddition reactions. A typical example of such a reaction is the cycloaddition of benzoate 116 and tosylate 128 with azete 126 (equations 78... 

Recently, Singh and co-workers reported an unprecedented Cu(I)/pybox-diPh-catalyzed highly enantioselective cascade alkynylation-lactamization reaction of readily available o-formyl methyl benzoates, aromatic amines, and terminal alkynes (Scheme 41) [66]. This protocol provides a straightforward and efficient approach to a wide range of enantiomerically enriched isoindolinones in good yield with an exceptionally high level of enantioselectivity. The methodology was further extended to the synthesis of synthetically important tetrahydroisoquinoline scaffolds in a two-step sequence with remarkable selectivity. 

Esters can also be useful protecting groups. Naoki Asao of Tohoku University developed Tetrahedron Lett. 2008, 49, 7046) the o-alkynyl ester 7. Au catalyst in EtOH removed the ester, leaving benzoates, acetates, OTBS and OTHP intact. Alternatively, an o-iodobenzoate can be removed by Sonogashira coupling followed by the Au hydrolysis. 

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