1.3- dicarbonyl compounds propargylation

The formation of an allenyl ketone as the sole product can be achieved by using an excess (2 equiv.) of propargyl bromide (entries 3—6, Table 5.9). Use of an increased amount (3 equiv.) of the acylzirconocene chloride in the reaction with propargyl bromide and/or tosylate yields a significant amount of a 1,4-dicarbonyl compound derived from Michael-type addition of the acylzirconocene chloride to the initially formed allenyl ketone (entry 2, Table 5.9). The Michael-type addition of acylzirconocene chlorides to allenyl ketones under Cu(I)-catalyzed conditions has been confirmed by an independent experiment (Scheme 5.31). 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

Cycloaddition between Propargylic Alcohols and Cyclic 1,3-Dicarbonyl Compounds... 

Related studies have recently been reported by the same author on propargyl steres reactions with dicarbonyl compounds or electron-rich arenes [135], to provide an atom-economical functionalization of carbon nucleophiles under catalytic conditions, using a very different method of addition catalyzed by Lewis acids [136]. 

Propargylation (8, 148-149). The propargylation of aromatics and /1-dicarbonyl compounds with (propargyl)dicobalt hexacarbonyl cations (I) is now used for selective alkylation of ketones and their Irimethylsilyl enol ethers and enol acetates. The reaction is regiospccific and involves attack of the more thermodynamically stable enol, In the case of ketones, yields are substantially reduced by use of a solvent. In the case of enol derivatives, CH2C12 can be used.1... 

Schulte and coworkers (62AP801) have prepared a number of 3-propargyl-4-hydroxy-2-pyrone derivatives (210) by condensation of /3-dicarbonyl compounds (208) with propargyl-malonyl chloride (209). On heating (210) with zinc carbonate, ring closure took place to give the corresponding furo[3,2-c]pyrone derivatives (211 Scheme 40). 

Direct treatment of propargyl halides with /3-dicarbonyl compounds and subsequent treatment of the products with zinc carbonate yields 2,3,5-trisubstituted furans. ... 

The thiolate-bridged diruthenium complex 101 can promote a cycloaddition reaction between propargylic alcohols and 1,3-dicarbonyl compounds to provide 3-acyM//-pyrans in excellent yield (Scheme 33). The reaction proceeds via formation and alkylation of the allenylidene complex 102 to form the vinylidene intermediate 103, which upon cyclization furnishes 4//-pyrans (Scheme 33) <2004JOC3408>. 

Tetraphenylantimony methoxide (Ph4SbOMe) reacts with 1,3-dicarbonyl compounds to generate tetraphenylantimony(v) enolates, which are readily alkylated by allyl, propargyl, and benzyl bromides as well as by ethyl bromoacetate (Equation (20)).54... 

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

A ruthenium-catalyzed three-component reaction between propargylic alcohols, 1,3-dicarbonyl compounds, and primary amines leading to fully substituted pyrroles was developed <07CEJ9973>. Cyclohexa[a]pyrroles ( azabicyclo[4.3.0] systems ) were formed by a three-component sequence involving allenic ketones, primary amines, and acryloyl chloride <07SL431>. An oxidative dimerization sequence involving arylpyruvates in the presence of ammonia was the key step in an approach to the pyrrole natural product, lukianol A <07S608>. 

Tetrasubstituted furans were obtained by a simple and efficient protocol starting from propargylic alcohols and 1,3-dicarbonyl compounds in the presence of a ruthenium-catalyst and CF3CO2H <07ASC382>. 

A metal-catalyzed tandem 1,4-addition/cyclization of propargyl alcohols with Michael acceptors such as alkylidene-malonates has been developed. In the presence of catalytic amounts of zinc triflate and triethylamine, various 2-alkylidene-l,3-dicarbonyl compounds react with propargyl alcohols to give 3- or 4-methylenetetrahydrofurans in excellent yields (Equation 96) <20040L2015>. 

The double conjugate addition of dithiols to propargylic ketones offers a facile route to [3-keto 1,3-dithianes that can function as masked 1,3-dicarbonyl compounds and provide access to spiroketals. When the alkynic substrate contains an additional electrophilic centre, a tandem eyclisation can accompany thiane formation (Scheme 30) <03OBC15>. 

In addition to their reactions with trlmethylsilyl enol ethers, (propargyl1um)Co2(C0)g complexes react with a variety of other mild carbon nucleophiles including activated aromatic compounds, g-dicarbonyl compounds, other enol derivatives (enol acetates and ketones directly), allylsilanes, and alkyl- and alkynyl-aluminum reagents. These reactions provide a flexible means to introduce the synthetically versatile propargyl function. Key features of propargylations using these complexes are 1) ready... 

Attyl and propargyl group transfer. Sulfinic acids or their sodium salts assist Pd(0)-catalyzed deallylation by accepting the allyl group. In addition to allylic esters, allylic sulfoximines can also deliver the allyl group to nucleophiles such as amines. Acrolein acetals react with 1,3-dicarbonyl compounds but the regiochemistry is strongly dependent on reaction temperatures. ... 

Furthermore, Bao and co-workers extended this methodology to include ben-zylic/propargylic C-H bonds as oxidative coupling partners to 1,3-dicarbonyl compounds [56]. 

Simple propargylic esters also undergo a 1,3-acyl migration catalyzed by Au(III), leading finally to 1,3-dicarbonyl compounds as mixtures of E and Z isomers (equation 26). ... 

Propargyl)Co2(CO)g radicals presumably are also involved in the Mn(III)-mediated addition of P-dicarbonyl compounds to complexed 1,3-enynes, which produces highly functionalized dihydrofiuan derivatives 122 (Scheme 4-65) [222, 223]. The chemo-, regio-, and stereoselectivity of these reactions stands in contrast to the variable selectivity associated with the corresponding reactions of free enynes [224]. The formation of ethers 123 in methanol (Scheme 4-65) suggests that the cobalt-propargyl radicals initially produced are rapidly oxidized by Mn(III) to the stabilized carbocations. 

Pentynones can be closed to furans using potassium t-butoxide or benzyl trimethylammonium methoxide. The base-catalysed 2-alkylation of 1,3-dicarbonyl compounds with propargyl halides, is followed in situ by 5-exo-dig ring closure. ... 

A Pd-catalyzed annulation of 2-propargyl-1,3-dicarbonyl compounds with vinylic or aryl triflates or halides in the presence of potassium carbonate yields 2,3-disubstituted 3-acylfurans (Equation... 

An interesting development in the lithiated cyanohydrin ether approach to acyl carbanion equivalents involves the [2,3] sigmatropic rearrangement of the anions derived from allyl- or propargyl-cyanohydrin ethers/ Scheme 2 shows an example of the application of this process in the synthesis of y-dicarbonyl compounds or their monoenol ethers. ... 

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