Esters, alkynic

The ester/alkyne rearrangement system can be extended by conjugation to involve a more distant site. The reaction of diethyl phosphorochloridate with 3-methylhex-4-yne-2-ene-l-ol leads to the vinylogous propargylic ester rearrangement as shown in Equation 4.39.176... 

The radical photoisomeiization of iodoacetylenic esters (alkynes) represents a route to iodoalkylidene lactones [68]. Zinc has been added to reduce side reactions and to increase yields of the photolysis reaction. Bromoalkynyloxiranes are photocatalytically (tri-n-butyltin) cyclized to allenylidene tetrahydrofurans [69]. 

After hydrozirconation with Cp2ZrEt2 and reaction with an chloroformic ester, alkynes directly (requiring no catalyst) afford conjugated esters. ... 

The activated ester alkyne-oxazole 200 underwent facile intramolecular Diels-Alder reaction in refluxing toluene with concomitant loss of acetonitrile to give an 89% yield of the desired tricyclic methyl ester 201. However, 201 could not be converted to the methyl butenolide 202 required to complete the synthesis. 

Muniz and co-workers prepared a series of substituted indoles (e.g., 76) using a modified Koser reagent that was made from iodosobenzene and 2,4,5-tris-isopropylbenzene sulfonic acid (77, TIPBSA). The hypervalent iodine reagent was used either stoichiometrically or in catalytic amounts with mCPBA as the terminal oxidant. A variety of N-protecting groups were tolerated and substituents on the aryl ring of 75 include halogens, carbonyls (aldehydes, ketones, esters), alkynes, and nitriles (HAG(I)7349). 

SCHEME 25.81. Oxidative cyclization of a tethered p-keto ester alkyne. 

Condensation is a class of oiganic reactions, where two molecules combine, usually in the presence of a catalyst, with elimination of water or some other simple molecule. The combination of two identical molecules is known as self-condensation. Aldehydes, ketones, esters, alkynes (acetylenes) and amines are among several organic compounds that combine with each other and except for amines, among themselves to form larger molecules, many of which are useftil intermediate compounds in organic syntheses. Catalysts conunonly used in condensation reactions include acids, bases, cyanide ion, and complex metal ions. 

CO. Alkynes will react with carbon monoxide in the presence of a metal carbonyl (e.g. Ni(CO)4) and water to give prop>enoic acids (R-CH = CH-C02H), with alcohols (R OH) to give propenoic esters, RCH CHC02R and with amines (R NH2) to give propenoic amides RCHrCHCONHR. Using alternative catalysts, e.g. Fe(CO)5, alkynes and carbon monoxide will produce cyclopentadienones or hydroquinols. A commercially important variation of this reaction is hydroformyiation (the 0x0 reaction ). 

Hydrides are available in many molecular sizes and possessing different reactivities. LiAIH reduces most unsaturated groups except alkenes and alkynes. NaBH is less reactive and reduces only aldehydes and ketones, but usually no carboxylic acids or esters (N.G. Gaylord, 1956 A. Haj6s, 1979). 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Several Pd(0) complexes are effective catalysts of a variety of reactions, and these catalytic reactions are particularly useful because they are catalytic without adding other oxidants and proceed with catalytic amounts of expensive Pd compounds. These reactions are treated in this chapter. Among many substrates used for the catalytic reactions, organic halides and allylic esters are two of the most widely used, and they undergo facile oxidative additions to Pd(0) to form complexes which have o-Pd—C bonds. These intermediate complexes undergo several different transformations. Regeneration of Pd(0) species in the final step makes the reaction catalytic. These reactions of organic halides except allylic halides are treated in Section 1 and the reactions of various allylic compounds are surveyed in Section 2. Catalytic reactions of dienes, alkynes. and alkenes are treated in other sections. These reactions offer unique methods for carbon-carbon bond formation, which are impossible by other means. 

No intennolecular reaction of malonate or /3-keto esters with halides has been reported, but the intramolecular reaction of /3-diketones such as 790 and malonates proceeds smoothly[652,653]. Even the simple ketone 791 can be arylated or alkenylated intramolecularly. In this reaction, slow addition of a base is important to prevent alkyne formation from the vinyl iodide by elim-ination[654]. 

The alkynyl ketones 840 can be prepared by the reaction of acyi chlorides with terminal alkynes, Cul in the presence of Et3N is the cocatalyst[719]. (1-Alkynyl)tributylstannanes are also used for the alkynyl ketone synthesis[720]. The a,. 3-alkynic dithio and thiono esters 842 can be prepared by the reaction of the corresponding acid chloride 841 with terminal alkynes[721,722]. 

A key intermediate, 163, which possesses all but one chiral center of (+ )-brefeldin, has been prepared by the enantiocontrolled cycloaddition of the chiral fi,/3-unsaturated ester 162 to 154[107], Synthesis of phyllocladane skeleton 165 has been carried out by the Pd-catalyzed cycloaddition of the unsaturated diester 164 and cobalt-catalyzed cycloaddition of alkynes as key reactions[108]. Intramolecular cycloaddition to the vinylsulfone in 166 proceeds smoothly to give a mixture of the trans and cis isomers in a ratio of 2.4 1[109], Diastereocontrolled cycloaddition of the hindered vinylsulfone 167 affords a single stereoisomeric adduct, 168, which is used for the synthesis of the spirocarbocyclic ring of ginkgolide[l 10],... 

Similarly to alkenes. alkynes also insert. In the reaction of 775 carried out under a CO atmosphere in AcOH, sequential insertions of alkyne, CO. alkene. and CO take place in this order, yielding the keto ester 776[483]. However, the same reaction carried out in THF in the presence of LiCl affords the ketone 777, but not the keto ester[484]. The tricyclic terpenoid hirsutene (779) has been synthesized via the Pd-catalyzed metallo-ene carbonylation reaction of 778 with 85% diastereoselectivity as the key reaction[485], Kainic acid and allo-kainic acid (783) have been synthesized by the intramolecular insertion ol an alkene in 780, followed by carbonylation to give 781 and 782[486],... 

In the coupling of the allenyl ester 7 with a terminal alkyne, an electron-deficient phosphine (Ph3P) gave the enyne-conjugated ester 8 as the major product, while an electron-rich phosphine (TDMPP or TTMPP) yielded the non-conjugated enyne esters ( )- and (Z)-9[4],... 

Propargylic (or 2-alkynyl) compounds are derivatives of alkynes. However, Pd-catalyzed reactions of propargylic derivatives, particularly esters and halides, are very different mechanistically from those of simple alkynes, except in a few cases. Therefore, the reactions of propargylic esters and halides are treated in this section separately from those of other alkynes. However, some reactions of propargylic alcohols, which behave similarly to simple alkynes, are treated in Section 6. 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

Using a catalyst system of PdCl2, CuCH, HCl, and O2, the internal alkyne 20 is carbonylated at room temperature and 1 atm to give unsaturated esters[19]. This apparently oxidizing system leads to non-oxidative cu-hydroesterilica-tion. With terminal alkynes, however, oxidative carbonylation is observed. 

Diaryl disulfides and diselenides add to alkynes to afford the (Z)-l, 2-bis(ar-ylthio)alkenes 193 and (Z)-l,2-bis(arylseleno)alkenes 194. Under CO pressure, carbonylative addition takes place to give thio esters and the selenoketones 195[I07], The selenoketones are converted into the /J-seleno-a, 3-unsaturated aldehydes 196 by Pd-catalyzed hydrogenolysis with HSnBu3[108,109],... 

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