Alkynyl Esters Research Articles

Electrotelluration: a new approach to tri- and tetrasubstituted alkenes.

A novel electrotelluration process is described in which a Michael addition of an alkyl or aryl tellurolate anion occurs onto an activated alkyne with subsequent trapping of a vinyl anion with electrophiles (aldehydes and ketones) other than a proton. This process provides an efficient regio- and stereospecific route to tri- and tetrasubstituted alkenes. Methodologically significant examples of this chemistry were studied in which aryl and alkyl tellurolate anions were added to omega-keto alkynyl esters in a Michael reaction, and the incipient vinyl anions were trapped intramolecularly by the internal aldehydes. The reactive centers were tethered by different lengths of alkyl chains to form highly functionalized five-, six-, seven-, and eight-membered rings in modest to good yields.

α-(N-Carbamoyl)alkylcuprate Chemistry in the Synthesis of Nitrogen Heterocycles

The conjugate adducts obtained via coupling of alpha-(N-carbamoyl)alkylcuprates with alpha,beta-ynoates, alpha-allenyl esters, or alpha.beta-enoates or enimides undergo N-Boc deprotection and cyclization onto the ester functionality upon treatment with PhOH/TMSCl, catecholboron bromide, or trimethylsilyl triflate. This two-pot sequence provides synthetic routes to 4-alkylidinepyrrolidine-2-ones, 4-alkylidinepyrrolizidin-2-ones, and 4-alkylidineindolizidin-2-ones via allenyl esters; pyrrolin-2-ones, tetrahydropyrrolizin-2-ones, and tetrahydroindolizin-2-ones via alpha/beta-ynoates; pyrrolidin-2-ones, pyrrolizidin-2-ones, and indolizidin-2-ones via alpha,beta-enoates or alpha.beta-enimides. The reluctance of gamma-carbamoyl-alpha,beta-enoates to undergo E/Z isomerization requires the use of (Z)-beta-iodo-alpha,beta-enoates readily prepared by the addition of HI to the alkynyl esters for the efficient preparation of pyrrolinones, tetrahydropyrrolizinones, and tetrahydroindolizinones. Utilization of omega-functionalized alpha,eta-ynoates or beta-iodo-alpha,beta-enoates allows for cyclization onto the omega-functionality providing for a synthetic route to quinolizidines.

A comprehensive study of [2 + 2] cycloadditions and ene reactions of alkynyl chromium and tungsten carbene complexes with enol ethers and ketene acetals and of the stereochemistry of the electrocyclic ring opening of cyclobutenyl carbene complexes

The reactions of several alkynyl carbene complexes [(CO)5MC(OMe)CCR1, M = Cr, W, R1 = Me, Me3Si, Ph, i-Pr, t-Bu) with a variety of acyclic enol ethers and ketene acetals [CH2C(OR2)R3, R2 = Et, Me, i-Bu, SiMe2t-Bu, R3 = H, Me, EtO, p-MeC6H4] are examined. These reactions occur to give [2 + 2] cycloaddition products in all cases except with R1 = Me3Si where ene products predominate. The cyclobutenyl carbene complexes produced in the [2 + 2] cycloadditions undergo rapid electrocyclic ring-opening at room temperature when R3 = H to give butadienyl carbene complexes as the isolated products. The reactions of the alkynyl carbene complexes with cyclic enol ethers derived from cyclohexanone and cyclopentanone are more prone to give ene products than the acyclic enol ethers. Greater proportions of ene products are seen for six- rather than five-membered ring enol ethers and for silyl rather than alkyl enol ethers and for silyl rather than carbon substituents at R1. Only small differences are seen between chromium and tungsten complexes. The [2 + 2] cycloadditions with the E- and Z-isomers of ethyl prop-1-enyl ether are stereospecific with complexes in which R1 = Me but not with those with R1 = SiMe3. The cyclobutenyl carbene complexes from the latter reactions with tungsten derivatives were found to undergo stereoselective electrocyclic ring-opening at 70 °C to give only Z,E-butadienyl carbene complexes which result from the conrotatory ring-opening in which the ethoxy group rotates in an outward direction. An E,E-isomer was also isolated from the thermolysis mixture; however, it was shown not to be a primary product but rather the result of an isomerization of the Z,E-butadienyl carbene complex under the reaction conditions. The stereoselectivity of the electrocyclic ring-opening of these cyclobutenyl carbene complexes was shown to be the same as that found for their corresponding cyclobutenyl esters. In one case, an interesting cine-rearrangement of a cyclobutenyl carbene complex was observed. The metal can be oxidatively removed from the cyclobutenyl carbene complexes to give the corresponding cyclobut-1-enyl esters in good yield. Thus, alkynyl carbene complexes can serve as synthons for alkynyl esters in [2 + 2] cycloadditions with enol ethers and have the attractive feature of greatly increased reaction rates. Additional synthetic interest can be associated with processes in which the [2 + 2] cycloaddition of the alkynyl carbene complex is coupled in tandem with other reactions of the carbene complex functionality in the cycloadducts. This is illustrated with Diels–Alder reactions of the butadienyl carbene complexes and cyclohexadienone annulations of a cyclobutenyl carbene complex.

Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by XTi(O-i-Pr)3 (X = Cl, O-i-Pr)/2i-PrMgBr Reagent. Efficient Synthesis of Functionalized Organotitanium Compounds from Unsaturated Compounds

Treatment of acetylenic or olefinic carbonates and esters with a low-valent titanium reagent diisopropoxy(η2-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)4 or ClTi(O-i-Pr)3 with 2i-PrMgX, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford organotitanium compounds having a carbonyl functional group, in good to excellent yields. Thus, the treatment of alkyl alkynyl carbonates 2 or alkyl alkenyl carbonates 4 with 1 gave organotitanium compounds having a lactone and/or ester group. Similarly, alkyl alkynoates 10 or alkynyl esters 14 of carboxylic acids reacted with 1 to give organotitanium compounds having a cyclic or acyclic ketone group, respectively. Thus, the reaction provides, after hydrolysis, five- or six-membered α-alkylidene lactones and/or α,β-unsaturated esters from 2, γ-butyrolactone derivatives from 4, five- or six-membered α-alkylidene cyclic ketones from 10, and acyclic α,β-unsaturated ketones 15 from 14. In all cases, the yields are excellent and the generation of the organotitanium compounds was confirmed by deuterolysis. The organotitaniums 6 and 11c reacted smoothly with iodine to afford 2-(iodomethyl)-4-butanolide (9) and α-[iodo(trimethylsilyl)methylidene]cyclopentanone, respectively. The organotitanium compounds obtained here also reacted with aldehydes to give the corresponding adducts, thus opening up a new access to substituted α,β-butenolides from 2, to γ-butyrolactones from 4, and to the corresponding tetrasubstituted furan from 10 and 14.

Synthesis of Homopropargyl Cycloalkanols by Pd-Catalyzed Samarium Diiodide-Promoted Intramolecular Coupling of Alkynyl Esters with Aldehydes and Ketones

Treatment of 1-(4-oxoalkyl)-2-alkynyl esters with SmI 2 /Pd 0 results in intramolecular cyclization to afford homopropargyl cycloalkanols. The same products are also obtained starting from isomeric γ-alkynyl- substituted lactol esters

Cycloadditions of alkynyl esters and ethers with 1,2,3-tri-t-butyl azete

Moderately electron-rich alkynes, such as alkynyl carboxylates 2a, b, siloxyalkynes 2c, d, an alkynyl p-toluenesulphonate 2e, and ethoxyacetylene 2f, add exclusively to the CN bond of the kinetically stabilized azete 1; with terminal alkynes 2a, f, a mixture of the regioisomeric 1-Dewar-pyridines 3 and 4 is obtained, whereas addition of internal alkynes results only in 3-oxy-1-Dewar-pyridines 3.

The interaction of alkynyl carboxylates with serine enzymes a potent new class of serine enzyme inhibitors

The recently reported alkynyl esters, propynyl benzoate and propynyl p-methoxybenzoate, were found to interact with a variety of serine enzymes. α-Chymotrypsin was inhibited very rapidly by an equivalent amount of the esters. Trypsin, elastase and pronase were also inhibited by the esters. On the other hand, liver esterase started to hydrolyse the alkynyl esters rapidly, but the enzyme became inhibited during the course of reaction. The inhibited enzymes exhibited slow reactivation which could be considerably enhanced by hydroxylamine.

Enantioselective hydrolyses by baker's yeast - III : Microbial resolution of alkynyl esters using lyophilized yeast

Both enantiomers of optically active 1-alkyn-3-ols were obtained in high optical purity by microbial resolution of their racemic acetates using a stable and ready-to-use lyophilized yeast preparation.