Alkynols esters

The most general approach to the preparation of functionalized acetylenes including acetylenic ethers involves elimination techniques, mostly dehydrohalogenation of appropriate olefin precursors (see Sections II.D.l and III.A.l). However, these and related procedures do not work for the preparation of alkynol esters 94-96, and this undoubtedly is one of the major reasons why these compounds remained unknown until the mid-1980s4 5. 

Reaction of alkynols 156 with benzenesulphenyl chloride afforded either the vinylacety-lene sulphoxides 157 or the allene sulphoxides 158 depending upon the substitution pattern of alkynols 156. Vinylacetylene sulphoxides 157 result from a [2,3]-allylic rearrangement of the sulphenate ester 159 (equation 88). In the case of the cyclic... 

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... 

Another possible termination step that has been utilized for the cycloetherification of alkynols involves CO insertion and esterification of the resulting acyl metal with an exogenous alcohol. This process has typically employed MeOH as solvent and a stoichiometric oxidant since the catalyst is turned over in a reduced form. Following this mechanistic motif, a variety of alkynols have been cyclized under Pd(n) catalysis to five- and six-membered oxacycles with incorporation of methyl esters into the products.294,327-329 For the formation of five-membered ring products, this reaction has been carried out in both exo- and endo-mode to provide 1- and 2-substituted... 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

The propargyl alcohols react with trivalent phosphorus halides to give allenic phosphorus esters as described in Scheme 3 and Table VI. In the case of aryl-substituted alkynols or highly hindered t-propargyl alcohols which contain no free acetylenic —H, thionyl halides or phosphorus trihalides yield bromo- or chloroallenes [74d], Thionyl chloride also reacts in a similar fashion with a wide variety of unhindered secondary alcohols (structure XV) to give a mixture of the chloroallene and chloroalkyne [74a-d]. 

Alkynolate anions.2 Treatment of the enolate anion 1 of a-chloroacetophenone with t-butyllithium (1.5-2.1 equiv.)3 in THF involves deprotonation to the dianion a followed by loss of Cl" and migration of the group on carbon to give the alkynolate anion b. The rearrangement was established by use of 3C. The anion b reacts with benzaldehyde to form the /Mactone c, which can be isolated as such or as the product 2 of hydrolysis. Quenching b with methanol affords the ester C6H5CH2COOCH3 (57% yield). 

Stable esters coming formally from alkynols and carboxylic, sulphonic or dialkyl phosphoric acids were prepared for the first time via alkynyliodonium salts with the corresponding anion. Several alkynyl carboxylates were obtained by anion exchange of alkynyl iodonium tosylates the initially formed salts, PhI+C=CR RCO2, were converted spontaneously into the esters on elution through a chromatographic column packed with an anion-exchange resin (Pol+ArCOj) ... 

Reaction of alkynol 401 with sulfur dichloride leads to alkynyl sulfmyl ester 402, which, when heated, rearranges to bisallenyl sulfone 403. Pyrolysis of 403 yields thiophene 1,1-dioxide 404 (Scheme 66) <1996LA171>. The reaction of bis-propargylic derivatives 405 with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) leads to dihydrobenzothiophenes 407 via a tandem cyclization of the intermediates 406 (Scheme 67) <2000TL2675, 2005JOC10166>. 

A similar approach had been reported earlier by Bestmann and coworkers" in their synthesis of hexadeuteriated leukotriene A4 methyl ester. C-alkylation of the tetrahy-dropyranyl ether of 3-butyn-l-ol with 2,2,3,3-tetradeuterio-l-iodopentane, prepared in 4 steps from propargyl alcohol, and subsequent protective group removal afforded the tetradeuteriated acetylenic alcohol 46 (equation 30). Semideuteriation of the alkynol and further transformation by known methods produced the labeled key reagent 3,4,6,6,7,7-hexadeuterio-(Z)-(3-nonen-l-yl)triphenylphosphonium iodide (47). Wittig olefination of epoxy dienal 45 with the labeled ylide generated from 47 completed the synthesis of... 

Three important processes have evolved from Reppe s work. Vinylation, the formation of vinyl derivatives by reaction of such compounds as acids, glycols, and alcohols with acetylene, produces the important vinyl esters and vinyl ethers. Ethinylation is defined as the reaction of acetylene with the carbon atom of a reactant without loss of the triple bond. A major application of the ethinylation reaction is to aldehydes and ketones to give alkynols and alkyndiols—e.g., the reaction of acetylene with formaldehyde to give propargyl alcohol and butyn-2-diol-l,4. Carboxylation (also referred to as carbonylation), the reaction of acetylene with carbon monoxide in the presence of metal carbonyls, has been applied to the production of acrylic acid, acrylates, and hydroquinone. 

Acetylenic ethers and esters represent an important class of functionalized acetylene derivatives of the hypothetical alkynols, RC=COH. The chemistry of acetylenic ethers has been well developed since their first preparation about 100 years ago Several exhaustive reviews covering the literature on acetylenic ethers and their analogs up to 1985 have been published in the last 30 years. In contrast to acetylenic ethers, esters of alkynols were unknown until the mid-1980s when the first preparation of alkynyl tosylates was reported. In the following years a wide variety of alkynyl carboxylate, phosphate and sulfonate esters has been prepared from alkynyl iodonium salts. The chemistry of these novel derivatives of alkynols has been summarized in a recent review. In the last 10 years considerable interest and research activity has arisen toward alkynols themselves and such derivatives as alkynolate salts and silyl ynol ethers. The present chapter will cover the chemistry of acetylenic ethers and esters as well as related derivatives of ynols with emphasis on new developments in this subject during the last 5-10 years. 

A recent approach to lithium alkynolates involves cleavage of some ynol ethers and esters with methyllithium Desilylation of silyl ynol ethers with methyllithium at room temperature in THF solution leads to the selective formation of the corresponding alkynolates (equation 9) k Similarly, alkynyl tosylates can be selectively cleaved with methyllithium at low temperatures (equation 10). ... 

Reactions of lithium alkynolates with dialkylchlorophosphates afford alkynyl phosphate esters as the major products (equation 14). However, reactions with acyl chlorides under similar conditions results in both O-acylation (product 20) and C-acylation (product 21) (equation 15). ... 

The reactions of alkynolates with alcohols leading to esters 26 also imply the intermediate formation of ketenes (equation 18). However, initial formation of ynols resulting from the O-protonation of the alkynolate anion and subsequent rearrangement to ketenes cannot be excluded. 

Reaction of lithium alkynolates with alcohols is especially useful for organic synthesis as a method of ester homologation . In this case ethyl esters of carboxylic acids 27 are used for the generation of lithium alkynolates in a multistep one-pot procedure (equation 19). Subsequent ethanolysis of lithium alkynolate in the presence of HCl gives homologated esters 28 in good yield. 

To date the most simple and general procedure for the preparation of silyl ynol ethers is the reaction of lithium alkynolates, generated in situ from ethyl esters, with silyl chlorides, according to equation 25 k However, this method (equation 25) does not work for the preparation of siloxyalkynes in which R is a lower alkyl group or hydrogen. Danheiser... 

More recently we have reported the preparation of alkynyl esters by the reaction of lithium alkynolates with the corresponding acid chlorides (equations 14 and 15, Section II.B.2). This method works well for the synthesis of alkynyl phosphates, however, it has only limited applicability in the preparation of alkynyl carboxylates. ... 

For example, malonic esters can be made by PTC carbonylation of ethyl chloroa-cetate at 1 bar CO at 25 °C in the presence of cobalt carbonyl. Ni(CN)2 was used for the PTC double carbonylation of alkynols, using PEG-400 as the phase-transfer catalyst, LaCls as an additional co-catalyst, toluene as the solvent, and 0.5 M NaOH as the optimum base concentration. Yields of ene-dicarboxylic acids were up to 97%. 

In order to synthesize the C5 acetate, dimethoxyacetone obtained by oxidation of acetone is ethynylated to 4,4-dimethoxy-3-methyl-l-butyn-3-ol in the presence of sodium hydroxide. Partial catalytic hydrogenation of the alkynol leads to 4,4-di-methoxy-3-methyl-l-buten-3-ol as the C5 alcohol which rearranges in acetie anhydride to the C5 aeetal ester. Deprotection of the aldehyde funetion necessary before the WiTTIG alkenylation is achieved thermally in the presence of copper(II)-salt as catalyst. 

Interestingly, it was found that the reactivity of formate esters is opposite to that of the alcohols described in the previous system (Eq. 23). Regioselective hydroesterification of alkynes and alkynols using formate esters and the catalytic system Pd(OAc)2-dppb-PPh3 in the presence of p-TsOH at 20 atm of CO gave unsaturated esters in good selectivity (Eqs. 23and24).t 2]... 

The Diels-Alder reactions of -deficient 2//-pyran-2-ones with vinyl moiety containing dienophiles under microwave and high pressures have been extensively reviewed. The microwave-initiated intramolecular Diels-Alder reaction of an alkynol with a furan (80) formed a cycloadduct (81) that readily converted to 3,4-disubstituted 5-hydroxyindoles (82) in 15-74% yields in a one-pot reaction (Scheme 23). ° The treatment of < rt/io-(trifluoromethanesulfonyloxy)aryl boronic acid pinacol ester (83) with t- or i-butyllithium generates arynes (85) via boronate intermediate (84) at... 

Heating compounds containing the system C C—C—S—C=C in hexa-methylphosphoramide (HMPA) gives 2if-thiopyrans (247). Isomeric thio-phens appear when the reaction is conducted in the presence of amines. Allene sulphoxides (248) are readily available by reaction of alkynols with sulphenyl chlorides to form labile sulphenyl esters, which rearrange to (248). The two chiral centres in these molecules (sulphoxide and allene) result in... 

Huh, K.T. Orita, A. Alper, H. (1993) Synthesis of dienoic acids and esters by cationic palladium complex-catalyzed carbonylation of alkynols and alkynediols, J. Org. Chem., 58,6956-7... 

The following steps were used to convert the (/ )-alkynol to the (i )-y,5-unsaturated ester. How would you convert the (/f)-alkynol into the (5)-y,5-unsaturated ester Red-Al, sodium feix(2-methoxye-thoxy)aluminumhydride, NaAlHjCOCH CH OCHj), is used to reduce alkynols to trans allylic alcohols [73]. 

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