Enol esters, from alkynes

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The rhodium-catalyzed enantioselective hydrogenation of enol esters is an alternative to the asymmetric reduction of ketones. Although enol esters are accessible both from ketones and alkynes, the number of studies reporting successful asymmettic hydrogenation has been limited. It appears that, compared... 

Scheme 4. Preparation of enol esters and dienyl esters from terminal alkynes and carboxylic acids.

The asymmetric hydrogenation of enol esters is an alternative to asymmetric ketone hydrogenation. The precursors can be prepared from the ketones but also via ruthenium-catalyzed addition of the carboxylic acids to the 2-postion of terminal alkynes. This latter method allows the study of the effect of the carboxylate on the enantioselectivity of the asymmetric hydrogenation. A remarkable study by Reetz and colleagues established that it is possible to hydrogenate enolate... 

As with other intramolecular ene reactions, this reaction is best suited to the preparation of cyclopentanes, but can also be used for the preparation of cyclohexanes. The reaction cannot be used for the formation of cyclopropanes or cyclobutanes since the unsaturated carbonyl compound is more stable than the ene adduct. 8,e-Unsaturated ketones (167) do not give cyclobutanes (171) by enolization to give (170) followed by a type I reaction but instead give cyclohexanones (169) by enolization to give (168) followed by a type II reaction. Alkynes can replace alkenes as the enophile. Enols can be prepared from pyrolysis of enol esters, enol ethers and acetals and from -keto esters and 1,3-dicaibonyl compounds. Tlie reaction is well suited to the preparation of fused or bridged bicyclic and spirocyclic compounds. Tandem ene reactions in which two rings are formed in one pot from dienones have also been described. The examples discussed below 2-i63 restricted to those published since Conia and Le Perchec s 1975... 

If the anions of these acids are good leaving groups, elimination from their enol esters can be effected by the bases used for elimination of hydrogen halides. Enol triflates, on treatment with pyridine (Scheme 46), 2,6-di-r-butyl phenoxide (Scheme 47) or potassium r-butoxide (Scheme 48) yield the corresponding alkynes. 

The electrophilic activation of terminal alkynes by arene-ruthenium(II) catalysts has provided selective access to enol esters. Enol esters are much more reactive than alkyl esters and have been used in a variety of reactions. In the past decade, Dixneuf and co-workers have developed selective approaches to the Markovnikov and antz-Markovnikov addition of carboxylic acids across alkynes by employing different arene-ruthenium(II) catalysts [48,53,54]. Of special interest is the synthesis of AT-Boc-protected 1-alanine isopropenyl ester 110 from N-Boc-l-alanine 108 and propyne 109 mediated by (Ty -cymene)RuCl2(PPh3) complex 107 (Scheme 30) [53]. Addition of the amino acid 108 to the propyne 109 proceeded exclusively in the Markovnikov sense and without accompanying racemization of the substrate. 

When 2-propargyl-l,3-dicarbonyl compounds are treated with aryl iodides under a balloon of carbon monoxide 2,3,5-trisubstituted-furans containing a 5-acylmethyl group (Scheme 7a) or its enol ester (Scheme 7b) can be obtained. Formation of the acyhnethyl derivative or its enol ester depends on the aryl iodide to alkyne ratio. Excess alkyne affords the acyhnethyl derivative as the main product whereas employment of an excess of the aryl iodide favors the formation of the enol ester. The enol ester product is very likely formed from the acyhnethyl product via trapping of the corresponding enolate with an acylpalladium complex. 

The enol esters obtained in this transformation can be further modified bearing in mind that they are protected aldehydes. Treatment of propargyl alcohols with benzoic acid in the presence of complex (dppe)Ru(2-methallyl)2 as catalyst affords the enol esters derived from the anti-Markovnikov addition of the acid to the alkyne (Scheme 6). Subsequent acid treatment gives rise to the conjugated enal, which is an isomer of the starting propargylic alcohol [80, 81]. 

Up to now one example of ruthenium-catalyzed addition of phosphinic acid to terminal alkynes has been reported. The Markovnikov additiOTi of diphenyl-phosphinic acid took place at 140°C with Ru3(CO)i2 (2.5 mol%) as catalyst precursor and geminal enol esters were obtained from phenylacetylene and various aliphatic acids in high yields (Scheme 21) [100]. 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

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