Alkynes ketone synthesis

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]. 

Abstract The basic principles of the oxidative carbonylation reaction together with its synthetic applications are reviewed. In the first section, an overview of oxidative carbonylation is presented, and the general mechanisms followed by different substrates (alkenes, dienes, allenes, alkynes, ketones, ketenes, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, phenols, amines) leading to a variety of carbonyl compounds are discussed. The second section is focused on processes catalyzed by Pdl2-based systems, and on their ability to promote different kind of oxidative carbonylations under mild conditions to afford important carbonyl derivatives with high selectivity and efficiency. In particular, the recent developments towards the one-step synthesis of new heterocyclic derivatives are described. 

A synthesis of the furanoeremophilane ( )-ligularone has been accomplished via the intramolecular Diels-Alder reaction of an oxazole with an alkynic dienophile (81JA4611). The lactone (359) was treated with lithium methylisocyanide to yield the oxazole (360). Oxidation of alcohol to aldehyde and reaction of this unstable aldehyde with lithiopropyne gave a 55 45 mixture of diastereomeric alcohols (361). Oxidation of the mixture gave a single alkynic ketone (362) which when refluxed in ethylbenzene afforded the desired furanosesquiterpene (363 Scheme 78). 

In 1973, it was demonstrated that 1,2-epoxystannanes, produced from vinylstannanes and MCPBA, could be isolated and characterized, in comparison widi 2,3-epoxystannanes (from allylstannanes), which are extremely reactive and have not been isolated (see Section 4.2.2.3). Subsequently, useful applications of 1,2-epoxy stannanes have been reported, including the internal alkyne ketone conversion, in the caibapenem and carbacephem 0-lactam antibiotic) skeletons. Ketone (10) should be of value in the construction of the biologically interesting l-carbapen-2-ene ring system. Synthesis of ketoacetates of potential use in the carbacephem system (e.g. 11 and 12) was also achieved by similar sequences shown in Scheme 11. ... 

A number of alkynic ketones have been reduced with the complex of LAH and (12) (1.1 2.5 equiv, ether, —78°C, 30-60 min) to give the corresponding (7 )-alcohols (Table 5). Johnson and co-workers have reported the reduction of ynone (17) to the (J )-alcohol in 84% ee and 95% yield with the LAH-Chirald complex. The resulting alcohol was an intermediate in an enantioselective synthesis of lla-hydroxyprogesterone. The thiophene ketone... 

A macrocyclic alkynic ketone has been protected as the Co derivative and then reduced with the complex of LAH with (12) (eq 1). Deprotection gave the (J )-alcohol (71% ee) which was an important intermediate in a synthesis of (+)-a-2,7,ll-cembratriene-4,6-diol. ... 

Bos and coworkers have developed several applications of alkyne-ketone photoadditions to organic synthesis. 2 Irradiation of a solution of acetone and 1-methylthio-l-propyne gives as a major product the cycloadduct (67) this results from selective oxetane formation due to radical stabilization by the methyl-thio group, followed by electrocyclic ring opening. Similarly, photoreaction of benzil and 1-t-butylthio-1-propyne gave the adduct (68) in 45% yield, which was transformed in 90% yield to the furan (69). 

The BINAL-H reduction works well with alkenic - and alkynic ketones affording alcohols with satisfactory optical purities (Scheme It is noteworthy that (S)-BINAL-H [(S)-(28)] reduces 1-halo-l-octen-3-one and 2-cyclopentene-l,4-dione to give the corresponding carbinols, which are important chiral building blocks for the synthesis of prostaglandins by the conjugate addition approach. ... 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

Several examples of alkynic ketone formation have been recorded since Weinreb s first examples. A Diels-Alder strategy for Ae synthesis of mevinolin required the preparation of alkynic ketone (24). Standard methods, calling for the addition of the alkynide anion to an aldehyde followed by oxidation, lead to extensive degradation and by-product formation. The Weinreb methodology was clearly more effective (Scheme 8). ... 

Jacobi s synthesis of ( )-paniculide-A involves an intramolecular Diels-Alder reaction of the alkynic ketone (31). This compound was prepared in >90% yield (Scheme 9) by acylation of a lithium alkynide with the A7-methoxy-A7-methylamide (30). Addition of the anion to other derivatives related to (30) such as an acid chloride, a trifluoroacetic mixed anhydride, an acyl imidazole, S-(2-pyridyl) thiolates and a mixed carbonic anhydride (from ethyl chloroformate) led to either bis-addition or to proton abstraction. Notice should be made of the stability exhibited by the A7-methoxy-A7-methylamide group while the oxa-zole moiety was being introduced. ... 

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