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]. 

It should be noted that the cyano group is lost by a retro-Claisen-type fragmentation 6->7 which gives automatically the pyrrocorphin 7 on the hexahydro oxidation level rather than by a /i-elimination-type process which would give a tetrahydroporphyrin. A similar fragmentation process has been observed in the total syntheses of chlorophyll a (sec Section 1.2.1.) and of a tolyporphin model (see Section 1.3). 

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). 

Claisen-type rearrangements of ester enolates, ketene acetals, and silyl ketene acetals... 

In a related example, reaction of N-hydroxy-N-methylthiophene-2-carboximidamide 56 with DMAD gave a double Michael addition product 57, which when heated at reflux in xylenes, afforded hydroxypyrimidinone 60 in 57% overall yield (Scheme 6.21) [9f]. The mechanism invoked was opening of the oxa-diazole 57 to 58, followed by a [3,3]-Claisen-type rearrangement to 59, which, after tautomerization and cyclization, afforded 60. 

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... 

A mixture of metals was utilized to promote a type Ilae synthesis of penta-substituted pyrroles <06OL2151>. Treatment of enyne 37 with a Ag(I) catalyst followed by BnNH2 and a Au(I) catalyst gave pyrrole 38 via a Claisen-type rearrangement and cyclocondensation. 

For the distillation, the still head consisted of a Claisen-type adapter with a parallel side arm (24/40 standard taper joints), 21 cm. high and 10.5 cm. wide. An ordinary straight still head is attached to the parallel side arm. This large still head prevents any bumping solid from entering the condenser. 

Allenes add nitrile oxides either to one or two double bonds. For mono- and 1,1-disubstituted allenes, relative activity of the two bonds depends on the nature of substituents. The reaction (Scheme 1.18) of N-propadienylanilines 54 with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide proceeds site- and regioselectively to give 5-substituted 4-methylene-4,5-dihydroisoxazoles 55, which add a second molecule of nitrile oxide to afford 4,5/-spirobi-(4,5-dihydroisoxazoles) 56. Dihy-droisoxazoles 55 isomerize to 4-(2-aminobenzyl)isoxazoles 57 via a Claisen-type rearrangement (224). 

The conversion of [49] into [50] involves a Claisen rearrangement. Once this was realized it was less surprising that no specific catalytic groups on the enzyme are involved. Support for the Claisen-type mechanism comes from the inhibition shown by the bicyclic dicarboxylate [51], prepared by Bartlett and Johnson (1985) as an analogue of the presumed transition state [52], This same structure [51], coupled through the hydroxyl group to a small protein, was used as a hapten to induce antibodies, one (out of eight) of which mimics the behaviour of chorismate mutase, albeit less efficiently (Table 7). 

Distilling flasks, ordinary and Claisen types, 25, 50, 100 cc.. one of each. 

The reaction of the thiolated PVC with Chloramine T carried out and the structure ( ) of the resultant polymer was examined (1 ). In the case of phenyl-thioether, the sulfilimine structure (2) was mainly produced accompanied with, in part, the sulfenamide structure (8,) binded to the main chain with N atom, the case of allyl thioether derivative containing C=C moiety in the pendent group, the sulfilimine (9) formed rearranged exclusively in Claisen type to the sulfenamide structure (10) connected to the main chain with S atom. 

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... 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

To participate in this sort of reaction, the carboxylic acid derivative acting as nucleophile must have a-hydrogens in order to generate an enolate anion. In practice, esters are most commonly employed in Claisen-type reactions. 

In nature, the biologically active form of acetic acid is acetyl-coenzyme A (acetyl-CoA) (see Box 7.18). Two molecules of acetyl-CoA may combine in a Claisen-type reaction to produce acetoacetyl-CoA, the biochemical equivalent of ethyl acetoacetate. This reaction features as the start of the sequence to mevalonic acid (MVA), the precursor in animals of the sterol cholesterol. Later, we shall see another variant of this reaction that employs malonyl-CoA as the nucleophile (see Box 10.17). 

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