Alkynic carboxylates, synthesis

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carbonylation. Two types of oxidative carbonylation of alkynes are known. The first one is the synthesis of alkynic carboxylates 211 by the oxidative carbonylation of terminal alkynes using PdCty and CuCty in the presence of a base [127]. Dropwise addition of the alkyne is recommended as a preparative-scale procedure of this reaction, in order to minimize the oxidative dimerization of alkynes as a competitive reaction [128]. The reaction has been applied to the synthesis of the intermediate 213 of the carbapenem 214 from the terminal alkyne 212 [129],... 

Yields and enantioselectivities are low in reactions with disubstituted alkynes. Asymmetric synthesis of lactams A rhodium catalyst with a chiral oxazolidinone ligand, dirhodium(ll) tetrakis[methyl 2-oxazolidinone-4 (S)-carboxylate] (1), can effect... 

Catalytic hydration and alcoholation of unsaturated compounds such as alkenes or alkynes would be a high value-adding step in the synthesis of compounds of complicated structure as well as in the large-scale production of industrially useful simple compounds. The activation of the O-H bond of water, alcohol, or carboxylic acid by transihon metals is relevant to a variety of such catalytic processes. 

Arndtsen and coworkers [154] described the first Pd-catalyzed synthesis of miinchnones 6/1-318 from an imine 6/1-316, a carboxylic acid chloride 6/1-317 and CO. The formed 1,3-dipol 6/1-318 can react with an alkyne 6/1-319 present in the reaction mixture to give pyrroles 6/1-321 via 6/1-320, in good yields. The best results in this four-component domino process were obtained with the preformed catalyst 6/1-322 (Scheme 6/1.83). 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (147) [123]. Pd-catalyzed carbonylation of bromobisthiophene 25, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 144, which was converted to iodide 145 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 145 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 146, which was subsequently hydrolyzed to 5 -(l-propynyl)-2,2 -bithienyl-5-carboxylic acid (147), a natural product isolated from the root of Arctium lappa. 

The reactions are related to the incorporation of CO and H20 into alkenes or alkynes leading to the corresponding saturated or unsaturated carboxylic acids. The general equation is shown below. Equation lb is related to the synthesis of acrylic acid discovered by Reppe [11]. 

The two major characteristic oxidation processes of alkynes are their transformation to 1,2-dicarbonyl compounds and their cleavage reaction to carboxylic acids.710 The structure of the starting compounds has a decisive effect on the selectivity of oxidation. Since 1,2-dicarbonyl compounds proved to be intermediates in further oxidations, carefully controlled reaction conditions are often necessary to achieve selective synthesis. Certain oxidizing agents such as peroxyacids and ozone are nonselective oxidants. 

The addition of carboxylic acids to alkynes affords enol esters which are useful as intermediates in organic synthesis.470 As in the addition to alkenes, a catalyst is usually required for high conversions of alkynes to enol esters. Simple acid catalysis has been employed (equation 279),471 but the more common catalysts are Lewis acids, such as boron trifluoride etherate,472 silver nitrate,473 zinc acetate474 and zinc oxide (equations 280 and 281),47S-476... 

In certain other systems, there is compelling evidence for the insertion into a metal-caiboxylate complex (equation 37). For example, in the synthesis of a-methylene-y-lactones from alkynic alcohols,70,71 no double bond rearrangement to a butenolide occurs, a reaction shown to take place in the presence of transition metal hydrides. The source of the vinyl proton (deuterium) on the a-methylene group is indeed the alcohol function. Finally, palladium carboxylate complexes containing alkynic (equation 40) or vinyl tails (equation 41) can be isolated and the corresponding insertion reaction can be observed. 

Functionalized cyclopropenes are viable synthetic intermediates whose applications [99.100] extend to a wide variety of carbocyclic and heterocyclic systems. However, advances in the synthesis of cyclopropenes, particularly through Rh(II) carboxylate—catalyzed decomposition of diazo esters in the presence of alkynes [100-102], has made available an array of stable 3-cyclopropenecarboxylate esters. Previously, copper catalysts provided low to moderate yields of cyclopropenes in reactions of diazo esters with disubstituted acetylenes [103], but the higher temperatures required for these carbenoid reactions often led to thermal or catalytic ring opening and products derived from vinylcarbene intermediates (104-107). 

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