Propargyl acetoacetates

The accessibility of nonracemic allyl acetoacetates makes the Carroll rearrangement an attractive strategy to assemble molecular complexity with adjacent tertiary and quaternary stereocenters. In the late 1950s, researchers at Hoffmann-La Roche utilised propargylic acetoacetate 194 to synthesise pseudoinone 195. Pyrolysis in the presence of Bronsted acid initiated the Carroll rearrangement to yield allenyl ketone 198 which tautomerised to pseudoinone 195. The minor product 196 resulted from Bronsted acid-mediated r-cation cyclisation of 199. 

Dienones from a-subst. propargyl acetoacetates s. 13, 900 Cerium carbonate... 

Bohlmann (207) reported the reaction of /I -dehydroquinolizidine with methyl vinyl ketone and with propargyl aldehyde forming a partially saturated derivative of julolidine 135 and julolidine (136), respectively. Compound 135 can be prepared also by mercuric acetate dehydrogenation of ketone 137, which is formed by condensation of 1-bromoethylquinolizi-dine with ethyl acetoacetate (Scheme 11). 

In 1985, Tsuji s group carried out a Pd-catalyzed reaction of propargyl carbonate with methyl acetoacetate as a soft carbonucleophile under neutral conditions to afford 4,5-dihydrofuran 109 [89-91]. The resulting unstable 109 readily isomerized to furan 110 under acidic conditions. In addition, they also reported formation of disubstituted furan 112 via a Pd-catalyzed heteroannulation of hydroxy propargylic carbonate 111 [92], Presumably, an allenylpalladium complex (c/. 114) was the key intermediate. 

In 1985, Tsuji s group carried out a Pd-catalyzed reaction of propargyl carbonate with methyl acetoacetate as a soft carbonucleophile under neutral conditions to afford... 

An extension of Tsuji s methodology has recently been reported by Liang in which he is able to perform a three-component coupling for the preparation of tetrasubstituted furans [154]. A combination of methyl or ethyl acetoacetate with propargyl bromide or carbonate and an aryl iodide enables the formation of tetrasubstituted furans 184. The proposed mechanism for this transformation is similar to that of Tsuji in that an allenyl-palladium intermediate is postulated. However, a three-component reaction is possible because the initial oxidative addition in this reaction is with the aryl iodide. Interaction of this Pd(II) intermediate with the propargyl bromide or carbonate leads to the allenyl-palladium species and, eventually, the product 184. 

Pd-Catalyzed three-component cyclization-coupling reaction of methyl acetoacetate, propargyl bromide or carbonate and aryl halides gave tetrasubstituted furans with high regioselectivities and good yields <05JOC6980>. 

Ketones with a-hydrogens react with the (propargylium)Co2(CO) complexes [175], undergoing regioselective alkylation at the more highly substituted a-position classical direct (e.g., enolate) and indirect (enamine, acetoacetic ester) methods for ketone propargylation are often complicated by the formation of allenic by-products. P-Diketones and ketoesters are also readily C-alkylated by 92 (Scheme 4-46) [176]. 

In contrast to facile Pd(0)-catalyzed reactions of allyl esters with soft carbon nucleophiles via r-allylpalladium intermediate, propargyl esters such as acetate are less reactive toward soft carbon nucleophiles. However, /3-keto esters and malonates react under neutral conditions with propargyl carbonates using DPPE as a ligand [37], Acetoacetate reacts with meAyl propargyl carbonate (119) in THF at room temperature to afford 4-(methoxycarbonyl)-5-methyl-3-methylene-2,3-dihydrofuran (120) in 88 % yield. The furan 121 was obtained by isomerization of the methylenefuran 120 under slightly acidic conditions. 

For a-aUylation and a-propargylation of carbonyl compounds, however, the Tsuji-Trost reaction and related reactions discussed extensively in Part V (Sect. V.2.1) provide a wide range of very satisfactory procedures. Although the Tsuji-Trost reaction has mostly been carried out by using extrastabilized enolates, such as acetoacetates and malonates, subsequent decarboxylation provides more usual a-substituted ketones (Scheme 3). 

Dicarbonyl compounds have featured in several approaches to dihydrofurans under a variety of reaction conditions. The palladium-catalysed reaction of propargyl carbonates with ethyl acetoacetate generates 4-methylene-4,5-dihydrofurans (57) in high yield (79-94%) in neutral media but the use of B-diketones leads to... 

Although direct oleflnation of l,4-dien-3-ones is synthetically difficult, an indirect route is now available conversion of the carbonyl to the propargyl alcohol, followed by catalytic Meyer-Schuster rearrangement using vanadyl acetoacetate [VO(acac)2]. Asymmetric alkoxyallylation of aldehydes has been achieved using a combined carbocupration-zinc homologation-allylation reaction in one pot. ... 

Unsubstituted methyl acetoacetate, bearing two active hydrogens, behaves differently. It reacts with methyl propargylic carbonate in a 1 1 ratio in THF at room temperature, giving an entirely different product (Scheme 25). In this case, at first C-alkylation of the central sp carbon of the allenylpalladium generates the 7r-allylpalladium intermediate bearing the... 

The mechanism of the furan formation can be explained by the following reactions. The reactions of isomeric 2-butynyl methyl carbonate and 1-methylpropynyl methyl carbonate with methyl acetoacetate give the same product, showing that furan formation from both carbonates proceeds via a common intermediate (Scheme 26). However, the reactions of the two isomeric propargyl carbonates with methyl 2,2-bisdeuterioacetoacetate give the products deuterated at different carbons namely, the 2-deuterio-3-hydrofuran is obtained from 2-butynyl carbonate. On the other hand, the reaction of 1-methylpropynyl carbonate with the... 

In general, Pd-catalyzed reaction of propargyl compounds provides synthetically valuable allenyl compounds through addition, transmetallation, or oxypalladation of allenylpalla-dium intermediates. Exceptionally, soft carbon nucleophiles such as malonate and methyl acetoacetate attack the sp carbon of allenylpalladium intermediates to afford allylic compounds and furan derivatives. 

According to a tentative mechanism as represented by the above (simplified) catalytic cy-de, the propargyl carbonate is transformed to a Pd-intermediate 90, which decarboxylates to the allenic moiety 93 after addition of the enolate of acetoacetate ( 92) and isomerization (92 91), the iT-allyl-Pd complex 91 cyclizes to the product 89. Highly functionalized tetrasubstituted furans can be prepared by a novel Pd-catalyzed three-component cycliza-tion of 2-alkinyl-2-alken-l-ones with an allyl chloride and an alcohol [30]. 

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