Ketones, conjugated from alkynes

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13... 

The reaction was rationalized by a ruthenium enolate mechanism (Fig. 4). Water served as a nucleophile and added to alkynes then the intermediate isomerized to give a ruthenium enolate, which then underwent addition to a-vinyl ketone followed by protonation to afford the 1,5-diketone. During the reaction, no ketone resulting from the hydration of the alkynes was found, which showed that the conjugate addition is faster than protonation of the ruthenium enolate in this aqueous reaction. 

Reduction of non-conjugated acetylenic ketones at constant current gives methylidenecy-clopentanols [Eq. (44)] [217]. The highest yields were obtained from terminal alkynes, and bicyclic systems could be formed from alkyne-functionalized cyclopeiitanones and cyclohexanones [217]. 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

Styrenes [103], conjugated aT-dienes [107], and aT-enynes [108] are also epoxidized with ketones 57 in high ees (Table 5, entries 9-14). No isomerization of the epoxides was observed therefore only c/x-epoxides were obtained from cis-olefins. Alkenes and alkynes appear to be effective directing groups to favor the desired transition states T and V (Fig. 19). 

Alkenylcatecholborane 11 is a good reagent for the conjugate addition and is easily obtained by the hydroboration of an alkyne with catecholborane. One-pot asymmetric synthesis of the conjugate addition product, /9-alkenyl ketone, is possible starting from an alkyne and catecholborane without isolation of the alkenylcatecholborane [12]. 

From a-substituted allylic alcohols, the formation of p,y-unsaturated ketones is favored, whereas conjugated enones are obtained from simple ally alcohol [46]. This transformation of terminal alkynes via coupling with allylic alcohol and formation of a C—C bond with atom economy has been applied to the synthesis and modification of natural compounds such as rosefuran and steroids [48, 49]. 

The photoaddition of alkanes onto electron-poor alkynes (e.g., propiolate or acetilendicarboxylate esters) can be accomplished by a radical conjugate addition reaction [7]. Radicals have been generated either via hydrogen abstraction from cycloalkanes or via electron transfer from 2-alkyl-2-phenyl-l,3-dioxolanes. In the first case, the irradiation was pursued on an alkane solution of an aromatic ketone (used as the photomediator) and the alkyne. Under these conditions, methyl propiolate was alkylated upon irradiation in the presence of 4-trifluoromethylacetophenone to form acrylate 48 in 97% yield (E/Z= 1.3 1 Scheme 3.31) [78]. 

In the photoaddition of a saturated hydrocarbon to ethyl propiolate (equation 19) it is likely that the excited state of the acetylenic ester initiates reaction by abstracting a hydrogen atom from the hydrocarbon. The addition of cyclic ethers to an alkyne seems similar (equation 20), although a ketone sensitizer is required for addition of tetrahydropyran or dioxan . When reactions of this type involve a conjugated acetylenic ester, the first-formed a,p-unsaturated ester can normally undergo further photochemical reaction to produce the p,y isomer (see equations 19 and 20). 

Muller and coworkers have recently developed a coupling-isomerization reaction, initially identified as a side reaction which occurred under standard Sonogashira conditions [79]. As demonstrated below, the coupling reaction is followed by a shuffling of oxidation states via an alkyne-allene isomerization [80]. The product, a,P-unsaturated ketone 146, is reminiscent of a product which would be obtained from a Heck reaction. The utility of this reaction was further demonstrated when diamine 147 was added to the reaction pot. Following a conjugate addition reaction and imine formation, compound 148 resulted from the three-component, one-pot reaction sequence enabled by the coupling-isomerization reaction. 

From the fact that in the reaction catalyzed by 2 also internal alkynes 24 can react to give ketones 25 (Scheme 8), the authors conclude that in this case no vinylidene complex acts as an intermediate. Apparently, its formation is favored by the presence of phosphane ligands, and in their absence other reaction paths are followed. The regioselectivity of the reaction as well as its yield can be increased if a mixture of water and DMF is used as solvent. The reaction functions also with alkynes whose triple bond is conjugated to an ester group. The chemoselectivity of the reaction was demonstrated by the coupling of a steroid side chain with an allyl alcohol one a,y0-unsa-turated carbonyl functionality present in the steroid part remained unaltered. 

Although the final yields of ketone are not high, i.e. they range from 50 to 67%, the reaction is very useful because it can be carried out on substrates with several other functional groups. For example, the reaction is successful when acetals, thioacetals, lactones, non-conjugated alkenes, epoxides, alcohols, and secondary bromides are present in the alkyne. 

---