Condensation, Claisen-type

Another well-established process to generate fluoro ketones proceeds via acylation ofenolates [68, 69] or activated methylene compounds [70 71] as well as by Claisen type condensation reactions [72] Because of the electrophilic power of the acylating agents, there is usually no need tor a catalyst [68]... 

The mechanism of the Madelung indole synthesis has not been fully established. An intramolecular Claisen type condensation is presumably involved in the process. ... 

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

As an extension of the reaction of sulphinates with organometallic compounds, the Claisen-type condensation between ketone enolate anions 101 and arenesulphinates may be considered. It was found161,162 that this reaction provides an interesting synthetic approach to a-ketosulphoxides 102 (equation 54 Table 9). 

CIDNP 874, 879, 1070 Claisen-type condensation 259 a-Cleavage, photochemical 875-877 Conjugate addition reactions 778, 783-785, 788... 

To accommodate this new finding and the previous results, we considered a new pathway (Scheme 3), in which acetate or its derivative condenses with arginine followed by decarboxylation. Such Claisen-type condensation on alpha-amino acid has some precedent in biochemical systems (6). To prove this hypothesis, we synthesized [2- C, 2-arginine and ornithine and fed to A, flos-aquae (5). 

A Lewis acid is also necessary for the acetylation of tetracarbonylferrate using N-acetylimidazole. In the absence of a Lewis acid, a Claisen-type condensation product was formed, which has been synthesized independently from 2 moles of A-acetylimidazole with sodium terf-butanolate in tert-butyl alcohol (55% yield) or with imidazole sodium in THF (95% yield) ... 

Nature gives us some illustrative examples of iterative methodologies in its biochemical mechanisms. The fatty acid-polyketide biosynthesis is one of them. The assembly of acyl units by sequential Claisen-type condensations to form a polyketide or fatty acid takes place at a multi-enzyme complex, at which the initial molecule is lengthened by one C2-unit per pass of a reaction cycle (Fig. 2). 

HO Me Claisen-type condensation Intramolecular Heck reaction... 

Acetogenins. Acetogenins are produced upon chain elongation with activated acetate units (or malonate followed by loss of carbon dioxide). A simplified sketch of this sequence is given in Fig. 1. During the first steps, a Claisen-type condensation of two acyl precursors yields a (3-ketoacyl intermediate A. Upon reduction to B and dehydration to C, followed by hydrogenation to D and hydrolysis, the chain elongated fatty acid E is produced. The next cycle will add another two carbons to the chain. Similarly, a reversed sequence leads to chain... 

Exercise 18-36 Show how the following substances may be synthesized by Claisen-type condensations from the indicated starting materials. Specify the reagents and reaction conditions as completely as possible. 

There are two main methods for the synthesis of monothio-/i-diketones, both affording yields in excess of 50%. The first method involves the passage of H,S through a dilute solution of the /5-diketone in ethanol, followed by the rapid passage of HC1 at — 70 °C the conditions are critical.184,183 The second method involves the Claisen-type condensation of ketones with thionic esters, RC(S)OMe, or dithionic esters, RC(S)SMe, in ether in the presence of sodamide.186-188 This method has the advantage that both isomers (46) and (47) can be prepared, whereas the first method yields only isomer (46) when R has a greater electron-withdrawing power than R. 

The first cyclative cleavage of a small molecule was Crowley and Rapo-port s study41 of intramolecular Dieckmann condensations on solid phase (Fig. 13), which was complicated by the reversible nature of the cyclization. Despite the unique opportunities afforded by C-C rather than C-X bond formation during cleavage, there are few examples from the combinatorial age. A modern version of the Claisen-type condensation by Kulkarni and Ganesan42 uses a strongly acidic active methylene group to ensure unidirectional cyclization, and furnishes tetramic acids with three points of diversity. 

Fig. 13. Cyclative cleavages based on Claisen-type condensations.

Al)-Acetyl-(A6)-aroyl-2,5-dithio-3,4,7,8-tetramethylglycolurils (92) and related compounds undergo a t-butoxide-catalysed Claisen-type condensation.268 Rate constants have been measured for the template-directed process, Hammett plots have been constructed, and deuterium isotope effects measured at the acetyl group. The... 

The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues has provided acyclic alkynes bearing a 1,3-diketone-type moiety.19 The reaction mechanism has been proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate (Scheme 2). 

Figure 6-17. The formation of a C-C bond using a Claisen-type condensation. A nucleophilic enol, enolate or enamine reacts with the electrophilic carbon of a carbonyl compound or an imine.

Trilithiated acetoacetanilides can undergo a Claisen-type condensation with benzoate esters to form initially pyran-4-ones, which can then undergo complex acid promoted rearangements to afford 277-pyran-2-ones (Scheme 157) <2004CJC659>. 

Synthesis of furochromone (55) was accomplished in 56% overall yield from a 5-acetyl-6-ethoxy-benzofuran via BF3 Et20-mediated deethylation (70%) followed directly by a Claisen-type condensation of the resultant hydroxyketone and EtOAc (Equation (27)) (89JOC4481). 

The biogenesis of flavonoids in plants is well documented and known to take place by chain extension of 4-hydroxycinnamoyl-CoA (126) with malonyl CoA through the acetate pathway involving enzymes like chalcone S3mthase (86). Here, the initially formed polyketide 127 may undergo a Claisen-type condensation to form a chalcone and subsequently other flavonoids, as shown in Fig. 25. It is pertinent to... 

The Claisen-type condensation of ketone enolate anions and arenesulfinates provides an interesting synthetic approach to diastereomeric ji-oxo sulfoxides69,70. 

Equimolar amounts of EDA and 48 give the corresponding lithium enolato complex which, by means of a Claisen-type condensation, leads to 49, which, in turn, reacts with [Zr(r 5-Cp)2(Me)Cl] to give 50 1... 

The Claisen-type condensation of acyl derivatives of o-toluidine furnishes a useful general synthesis of indoles. 

Auxiliary cleavage with concomitant carbon-carbon bond formation is a particularly attractive option, which has been demonstrated in a bimolecular sense using the dianion of methyl sulfone (giving a methyl ketone), and in an intramolecular sense using a Claisen-type condensation of a p-acetoxy enolate (giving a 5-lactone). An interesting halolactonization procedure has... 

In the presence of a strong base, e.g., lactam anions, the imide groups containing at least one ct-hydrogen undergo a Claisen type condensation analogous to the condensation of esters or ketones [121, 125], viz. 

---