β‐Methyl‐verzweigte α.β‐ungesättigte Carbonsäuren durch nucleophile Addition von β‐Dicarbonylverbindungen an monosubstituierte Acetylene

Abstract

Sowohl Brommalonsaure-diathylester (1 a) und Phenylacetylen (3a) als auch Malonsaurediathylester (8a) und 2-Brom-1-phenyl-acetylen (7a) setzen sich in Gegenwart von Zink in Xylol unter nucleophiler Addition des intermedilr entstehenden Zink-monobromid-malonsaure-diathylesters (2a) iiber die Zwischenstufen 4a und 5 a zum p-Methyl-a-athoxycarbonylzimtsaure-athylester (6a) urn, aus dem durch Verseifung und Decarboxylierung die P-Methylzimtsaure zu erhalten ist. Wird anstelle von Malonester Methylrnalons~ure-diathylester (8b) eingesetzt, so bleibt die Reaktion auf der Stufe des Buten-(3)-saureesters 5b stehen. Als Nebenprodukt entsteht dabei der Butin-(3)-saureester 9 b. Als P-Dicarbonyl-Komponente konnen Acetessigsaure-oder Benzoylessigsaure-iithylester, auch Acetylaceton eingesetzt werden, jedoch nehmen die Ausbeuten mit deren steigendem Enolgehalt ab. Aus 1-Alkinen (13) entsteht mit l a das Additionsprodukt 15, aus dem nach Verseifung und Decarboxylierung 3-Methyl-alkensauren in den drei isomeren Formen 17, 18 und 19 entstehen, ein weiteres Beispiel fur Drei-Kohlenstoff-Prototropie. p-Methyl Branched a.p-Unsaturated Carboxylic Acids by Nucleophilic Addition of p-Dicarbonyl Compounds to Monosubstituted Acetylenes l)Reaction of diethyl bromomalonate (la) with phenylacetylene (3a) as well as reaction of diethyl malonate (8a) with 1-bromo-2-phenylacetylene (7a) in the presence of zinc in xylene involves nucleophilic addition of the zinc monobromide of diethyl malonate (2a), formed as an intermediate via 4a and 5a, to yield P-methyl-a-(ethoxycarbonyl)cinnamic acid diethyl ester (6a), which on saponification and decarboxylation affords P-methylcinnamic acid.If the malonate is replaced by diethyl methylmalonate (Sb), the reaction stops at the stage of 3-butenoic acid ester 5b. In this reaction 3-butynoic acid ester 9b is formed as a by-product. The analogous reaction is given by ethyl acetoacetate, ethyl benzoylacetate and acetylacetone; the yields decrease with increasing enol content of the P-dicarbonyl compounds. The addition product 15 obtained by the reaction of 1-alkynes (13) with l a yields on saponification and decarboxylation 3-methylalkenoic acids. The latter occur in the three isomeric forms 17, 18 and 19, presenting another example of a three-carbon prototropy.Die aktivierte Dreifachbindung geht bekanntlich leicht nucleophile Additionsreaktionen ein. So lassen sich z. B. Alkyllithium-Verbindungen und anionisierte p-Dicarbonylverbindungen anlagern, nicht aber Grignard-Verbindungen 2). Es war naheliegend, die Reaktion von monohalogensubstituierten P-Dicarbonylverbindungen unter den Bedingungen der Reformatsky-Reaktion mit der aktivierten Acetylenbindung zu 1) Teil der Dissertation J. Feldkamp, Univ. Munster 1970.2 ) F. Bohlmann, Angew. Chem. 69, 82 (1957).

Addition of Metal Enolate Derivatives to Unactivated Carbon−Carbon Multiple Bonds

“…Interestingly, a similar reaction was observed between diethyl malonates and 1-halo-2-phenylacetylenes (Scheme 226). 336,338 In this case, the alkynyl-Zn reagent formed by zinc insertion into the carbon-halogen bond deprotonates the malonate which then adds onto the alkyne, with the addition taking place at the internal position of the alkyne, as observed above.…”

“…Zn-enolates of malonate derivatives and β-cyano esters have also been reported to add onto terminal alkynes. In a first report by Schulte and co-workers, 336 diethyl bromomalonate was shown to react with alkyl-and aryl-substituted terminal alkynes in the presence of zinc metal to give alkylidene-and benzylidenemalonate derivatives in low to moderate yields (Scheme 224).…”

Carbozincation Reactions of Carbon–Carbon Multiple Bonds

“…65 Nucleophilic addition of the zinc enolate derived from diethyl bromomalonate to phenylacetylene in refluxing xylene is one of the first reports of the addition of stabilized zinc enolates across alkynes (Scheme 27). 66 The reaction is usually regioselective and affords the branched isomer. 17 However, when the steric hindrance becomes more important at the propargylic position, as in the case of propargylic ethers or substituted amines, the formation of an increased amount of the linear constitutional isomer is observed (Scheme 28).…”