Alkylidenation carboxylic acid derivatives

Second, titanium-based reagents are suitable for methylenation or alkylidenation of carbonyl groups of carboxylic acid derivatives such as esters and amides (Equation (7)). ... 

Other electrophiles, such as Michael acceptors, can also be involved in the a-alkylation step. This has been exploited in the conjugate addition of enantiopure lithium amides 60 to unsaturated esters 61, followed by trapping of the resulting enolate with alkylidene malonates. This constitutes a useful methodology for the asymmetric synthesis of p-amino-a-substituted carboxylic acid derivatives 62 (Scheme 11.24) [65]. 

Alkylidenation of Aldehydes, Ketones, and Carboxylic Acid Derivatives... 

Alkylidenation with a thioacetal-titanocene(II) system is useful for the conversion of carboxylic acid derivatives into enol ethers, alkenyl sulfides, and enamines. As with other titanium-based reagents, mixtures of stereoisomers are formed in... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

Hartley, R. C., McKiernan, G. J. Titanium reagents for the alkylidenation of carboxylic acid and carbonic acid derivatives. J. Chem. Soc., Perkin Trans. 1 2002, 2763-2793. 

Enolates derived from cyclic compounds such as cyclohexane carboxylic acid or cyclohexane carboxalde-hyde generate enolates that are unique. These enolates have an exocyclic double bond that can exist as ( ) and (Z) isomers. The facial and orientational bias in alkylation and condensation reactions of such enolates is influenced by the conformation of the ring it is attached to. Alkylidene cyclohexane enolates show a preference for equatorial attack, just as cyclohexanone derivatives do (sec. 4.7.C,D). 

Closely related chemistry has permitted the development of an enantioselective synthesis of certain classes of carboxylic acids.The key reagent is the oxazoline 7, which is commercially available in optically active form. The oxazoline condenses with aldehydes to give the alkylidene derivatives 8. The alkylidene intermediates can undergo conjugate addition of organolithium reagents in a highly stereoselective... 

Not only acylimino acids (VI. B.) but also 2-alkylidene- and 2-aryli-dene-A -oxazolin-5-ones (55) (pseudooxazolones) add nucleophiles. Simultaneous ring opening is usually observed 195, 237, 238, 239, 397) yielding the corresponding amino acid derivatives. Reaction with ammonia or amines resp. alcohols yields a,a-diamino carboxylic acid esters (56) or a-alkoxy-a-acylaminocarboxylic acid esters (58) respectively. Mercaptans add so rapidly that mercaptooxazolinones (57) can be isolated and then opened with other nucleophiles. 

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