Alkynyl ketones

The carbonylation of aryl iodides in the presence of terminal alkynes affords the acyl alkynes 565. Bidentate ligands such as dppf give good results. When PhjP is used, phenylacetylene is converted into diphenylacetylene as a main product[4l5]. Triflates react similarly to give the alkynyl ketones 566[4I6], In... 

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]. 

Recently the Bohlmann-Rahtz synthesis has received greater attention. Baldwin has employed this method for the construction of heterocyclic substituted a-amino acids. Exposure of alkynyl ketone 39 to 3-aminocrotoyl ester 40 resulted in the Michael product 41. Thermolysis then gave rise to the desired pyridyl-P-alanines 42. 

Moody s synthesis of promothiocin 43 provided evidence that the Bohlmann-Rahtz method can be used for the rapid synthesis of complex pyridines. Oxazaole 44 was treated with alkynyl ketone 45 to afford 46 in 83% yield. The ester moiety of 46 was elaborated into a thiazole substituent providing entry into the northeast quadrant of 43. 

Treatment of 210 under traditional Eschenmoser fragmentation conditions gave only low yields of the desired alkynyl ketone 211, but this result was improved significantly by use of p-nitrobenzenesulfonylhydrazine in place of the commonly used p- lolueriesul fonylhydrazine. Compound 211 was transformed into the bis-oxime 212, reductive cyclization of which by treatment with ZrCU and NaBH4 and subsequent acylation afforded the polycyclic compound 213 with the desired all-cis... 

Pyridines 158 have been also prepared by cyclocondensation of alkynyl ketones 157 and amino acrylates in DMSO as the solvent at 170 °C for 20 min (Scheme 56 and Sect. 5.2 for more details) [102,103]. 

Alkynyl ketones 157 were also used for the synthesis of pyrimidines 159 by reacting amidines in acetonitrile at 120 °C in a dedicated microwave synthesizer without the requirement of additional purification (Scheme 56) [104]. 

Scheme 56 Synthesis of pyridines and pyrimidines from alkynyl ketones...

Dieter developed a flexible two step synthesis of substituted pyrroles involving initial Beak deprotonation of /ert-butoxycarbonyl (Boc) amines 36 followed by addition of CuX-2LiCl (X = -Cl, -CN) to afford a-aminoalkylcuprates. Such cuprates undergo conjugate addition reactions to a,(3-alkynyl ketones affording a,(3-enones 37, which upon treatment with PhOH/TMSCl undergo carbamate deprotection and intramolecular cyclization to afford the pyrroles 38 . 

Cyclocondensation processes of p-dicarbonyl derivatives or their analogues are still widely employed for the synthesis of new isoxazoles. Non-proteinogenic heterocyclic substituted ct-amino acids have been synthesised using the alkynyl ketone functionality as a versatile building block ynone 2, derived from protected L-aspartic acid 1, reacted with hydroxylamine hydrochloride affording the isoxazole 3 with enantiomeric purity greater than 98% ee <00 JCS(P 1 )2311 >. 

Recently, the silane-mediated reductive cyclization of activated alkynes with tethered ketones using Stryker s reagent as a catalyst was reported.112,90b Alkynyl ketone substrate 84a was treated with a catalytic amount of Stryker s reagent in the presence of polymethylhydrosiloxane (PMHS) to afford the cA-fused hydrindane 84b as a single diastereomer. This method is applicable to both five- and six-membered ring formation, but often suffers from competitive over-reduction of the reaction products (Scheme 59). 

Nakamura et al.141 reported a closely related reaction, that is, the enantioselective addition of allylzinc reagent to alkynyl ketones catalyzed by a bisox-azoline catalyst 137. High ee values were obtained in most cases (Scheme 2-55). 

E,E)-a,P Y,5-Drenones.2 Aryl a,(3-alkynyl ketones rearrange in the presence of this ruthenium catalyst in refluxing toluene to conjugated (E,E)-dienones in 75-85% yield. A similar rearrangement with alkyl a,(i-alkynyl ketones proceeds less readily. 

The last question still open addresses the alkynyl ketones. The reaction of 64 shows an example with a potential intramolecular competition and here it is possible to isomerize the propargyl substitutent on the ketone quantitatively without changing the 1-hexynyl substituent on the other side [125] (Scheme 1.28). From the publication it is not clear whether the isomerization is really a thermal reaction or occurs during the workup of the thermolysis reaction, for example by chromatography (compare the discussion above [110]). 

When alkynyl ketones are synthesized, occasionally an in situ isomerization to the allene was reported, for example in the propargylic ether 66 [126] (Scheme 1.29). 

A little-explored route to allenylsilanes utilizes tosylhydrazone derivatives of tri-methylsilyl alkynyl ketones [52]. Treatment with NaBH3CN in acidic medium leads to transient propargylic diazines, which rearrange with loss of nitrogen (Eq. 9.44). 

Gevorgyan and co-workers demonstrated that allenyl imines can be formed in situ by treating alkynylimines with a base (see Section 15.8, compound 185) [71, 72]. The same principle also works for the in situ formation of allenyl ketones from alkynyl ketones and their conversion to furans with a copper(I) catalyst [71, 72]. That Cu(I) would catalyze the isomerization of an allenyl ketone was known from work of Hashmi et al. [57, 58],... 

Alkynyl ketones 63 are reduced to chiral propargylic alcohols with the same reagent in high optical and synthetic yields (82). The results are shown in Table 7. Reagent (S)-56 gave (S)-alkynylcarbinols, whereas (R)-56 gave the (R)-al-cohols. Several of the acetylenic alcohols are useful for transformation into insect pheromones. 

Scheme 3.41. Reactions between a-aminoalkylcuprates and alkynyl ketones [163] or esters [161b], and formation of pyrroles and pyrrolidinones (Boc = t-butoxycarbonyl).

In the hydroboration of terminal alkenes, carrying a ketone or aldehyde group, with a variety of borane reagents, dicyclohexylborane has been identified as the most efficient reagent. Analogous hydroboration of alkynyl ketones and alkynyl aldehydes with dicyclohexylborane yields the corresponding olefinic carbonyl compounds after protonation, or dicarbonyl compounds after oxidation. ... 

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