Ketones alkynyl, formation

Cyclization of alkyl o-(l-alkynyl)aryl ketones. The formation of a 3-alkyl-1-... 

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

C. Reactions not involving P=0 or P=S Groups.—Enamine phosphine oxides (45) have been prepared by the addition of amines to 1-alkynyl-phosphine oxides, and the reactions of their anions with various electrophiles have been reported. - With ketones a Wittig-type reaction leads to the formation of a/3-unsaturated ketones, in 53—70% yield, while with epoxides cyclopropyl ketimines are formed. A Diels-Alder reaction of l-phenyl-A -phospholen-l-oxide (46) with 1,4-diacetoxybutadiene has been used in the preparation of l-phenyl-benzo[/>]phosphole (47), as... 

Scheme 10.1 gives some representative examples of laboratory syntheses involving polyene cyclization. The cyclization in Entry 1 is done in anhydrous formic acid and involves the formation of a symmetric tertiary allylic carbocation. The cyclization forms a six-membered ring by attack at the terminal carbon of the vinyl group. The bicyclic cation is captured as the formate ester. Entry 2 also involves initiation by a symmetric allylic cation. In this case, the triene unit cyclizes to a tricyclic ring system. Entry 3 results in the formation of the steroidal skeleton with termination by capture of the alkynyl group and formation of a ketone. The cyclization in Entry 4 is initiated by epoxide opening. 

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). 

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],... 

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

With terminating alkynyl groups, vinyl cations are formed. Capture of water leads to formation of a ketone.19 20... 

Besides electrophilic addition, terminal alkynes also perform acid-base type reaction due to acidic nature of the terminal hydrogen. The formation of acetylides and alkynides (alkynyl Grignard reagent and aUcylnyllithium) are important reactions of terminal alkynes (see Section 4.5.3). Acetylides and alkynides undergo nucleophilic addition with aldehydes and ketones to produce alcohols (see Section 5.3.2). 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Isotellurazoles 4 were obtained in low yields (3-11%) by the one-pot reaction of alkynyl ketones with hydroxylamino-O-sulfonic acid and K2Te in aqueous solution containing sodium acetate (83S824 87H1587). A plausible mechanism of the reaction includes formation of the oxime derivative and subsequent nucleophilic addition of telluride anion to the triple bond followed by cyclization to 4. The reaction is accompanied by the formation of telluro bis(alkenyl ketones) 5 in yields approximately equal to those of 4. When alkynyl aldehydes are used instead of ketones, the single reaction products are the tellurobis(alkenyl nitriles) 6 (83S824). 

The formation of the allyl ketone 421 is explained by the following mechanism. The Ru alkynyl complex 423, formed by oxidative addition, isomerizes to the Ru vinylidene complex 424. Nucleophilic attack of allyl alcohol to the electron-deficient. vp-carbon of 424 generates the allyloxycarbene complex 425, which is converted to... 

This simple sketch illustrates clearly that convergent multicomponent reactions performed with a limited set of reactive building blocks (reactophores) in a multigeneration format offer a tremendous potential to produce diverse small-molecule compound collections, depending on the reaction sequence used (the combinatorics of reactive building blocks ). The concept of combinatorics of reactive building blocks should ultimately lead to novel multicomponent reactions. In Section III we will focus on reactophores such as a-alkynyl ketones, which allow the construction of a wide variety of core structures. 

In contrast to (diacetoxyiodo)benzene, [bis(trifluoroacetoxy)iodo]benzene, (BTI) reacts in aqueous solvents with both terminal and non-terminal alkynes affording eventually a-hydroxyketones and 1,2-diketones, respectively. The primary reaction of terminal alkynes leads to the formation of alkynyl phenyliodonium salts, which are not isolable under the experimental conditions but have been prepared by other routes (Section 9.1.3) these are hydrolysed in situ to a-hydroxymethyl ketones, through the intermediacy of their O-tri fluoroacetates, which sometimes may be isolated as by-products. 

The ability of the ethynyl-l,5-azastibocines 5, to be used as alkynylation agents, has recently been demonstrated by Kakusawa et al. <2003TL8589>. The reaction of 5 with organic halides, such as acyl halides and aryl halides, in the presence of PdCl2(PPh3)2, as a catalyst, led to the formation of cross-coupling products, alkynyl ketones 109 and diaryl acetylenes 110, in good yields (Equations 9 and 10). 

U.v. irradiation of the unsaturated A-seco-5-ketone (324) gave none of the expected oxetan (325), but instead produced the cyclobutanols (327) as major products, along with a little of the B-seco decarbonylation product (328). Cyclobutanol formation proceeds through hydrogen transfer from C-2 to the carbonyl oxygen, which is followed by cyclization of the 2,5-biradical (326). Similar reactions occur with the alkynyl-ketone (329) and with the saturated analogue (330). ... 

Some applications of FTIR are shown in Figure 7.7. The classic example of using in-line FTIR is the Merck investigation of [5-lactam formation [13]. The reaction was shown to proceed through the ketene intermediate 21. FTIR was also used to determine optimal conditions for the low-temperature alkynylation of the ketone 22 [14] and for the methylation of indole 23 [15]. The conversion of phenol 24 to carbamate 25 and isothiocyanate 26 was conveniendy monitored by FTIR [16] due to the hot temperature and reactive nature of the reaction components, special handling would have been required to withdraw reaction aliquots and prepare samples. 

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