Alkynyl phosphate esters

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). ... 

Alkynyl(phenyl)iodonium sulfonates are stable, microcrystalline substances that can be stored and used indefiniteiy with little or no decomposition. They have been employed in the formation of aryl (2-furyl)iodonium tosylates, alkynyl sulfonate, carboxylate and phosphate esters, tricoordinate vinyliodinane species,fO and alkylidenecarbene-iodonium ylides. <... 

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... 

One route to (l-alkynyl)phosphonic esters depends on the base-catalysed destruction of enol phosphates (123) obtained in situ from (2-oxoalkyl)phos-phonates in the case of (123) (R = Et), a mixture of (1-butynyl)- and (2-butynyl)-phosphonic esters was obtained, but in all other quoted cases only the acetylenic compound was obtained. A second route starts with diethyl (trichloromethyl)-phosphonate (a reagent of increasing synthetic importance) followed by sequential reaction in one-pot with BuLi (two equivalents), an aldehyde (RCHO), and a lithiumdialkylamide, and gives the products (Et0)2P(0)CsCR in very high yields. ... 

The reaction of alkoxide ions with alkynyliodonium salts is unproductive, leading to only decomposition products rather than the desired alkoxyacetylenes. Similarly, reaction of R3SiO does not lead to any siloxyalkynes. In contrast the softer sulfonate, carboxylate, and phosphate nucleophiles all readily react with alkynyliodonium salts leading to the corresponding alkynyl sulfonate, carboxylate and phosphate esters [4]. 

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]. 

In a similar manner, decomposition of alkynyl(phenyl)iodonium phosphates 98 affords acetylenic phosphate esters (equation 64) . This reaction does not require any catalyst, since alkynyl(phenyl)iodonium phosphates 98 are substantially less stable than tosylates 97, and smoothly decompose upon standing at room temperature for a few hours in CH2CI2 or CHCI3 yielding alkynyl phosphates 95 and iodobenzene as the by-product. 

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. ... 

A wide variety of aryl iodides undergo palladium catalyzed coupling with tert-butyl ethynyl ether giving intermediate tert-butyl arylethynyl ethers which upon in situ thermolysis in toluene containing morpholine give intermediate aryUcetenes that are captured as the morpholinyl esters (Scheme 4.22). Alkynyl phosphates act as nucleophiles toward histidine residues in phosphotriesterase under physiological conditions, and this has been proposed to involve ketene formation in a phosphotriesterase catalyzed reaction (Eqn (4.61)). ... 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

Reaction with an amine, AIBN, CO and a tetraalkyltin catalyst also leads to an amide.Benzylic and allylic halides were converted to carboxylic acids electroca-talytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions.Allylic (9-phosphates were converted to allylic amides with CO and ClTi=NTMS, in the presence of a palladium catalyst. Terminal alkynes were converted to the alkynyl ester using CO, PdBr2, CuBr2 in methanol and sodium bicarbonate. ... 

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. 

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