Base-Promoted Condensations

One of the syntheses of f1 udalanine begins with base promoted condensation of ethyl fluoroacetate and ethyl oxalate to give This is then converted by hydrolytic processes to the insoluble hydrated lithium salt of fluoropyruvate (58). This last is reductively aminated by reduction with sodium boro-deuteride and the resulting racemate is resolved to give D-flu-dalanine (59). 

Base-promoted condensation of ketones with 3-nitroaniline results in the formadon of indoles. The reacdon proceeds in one pot via a NASH-type reacdon and subsequent cyclizadon fEq. 9.55. ... 

The most widely applied precursors for the synthesis of monocyclic NHPs are a-diimines which can be converted to the target heterocycles either in a two-step reaction sequence involving two-electron reduction of the diimine to an enediamide, enediamine, or a-aminoamine and subsequent condensation with PC13 [18-20] or a dichlorophosphine RPC12 [21], or via direct base-promoted reaction with PC13 [20, 22], The latter reaction involves addition of a P-Cl bond to each imine moiety followed by base-promoted elimination of hydrogen chloride leading to 2,4-dichloro-... 

Darzens reaction of (-)-8-phenylmethyl a-chloroacetate (and a-bromoacetate) with various ketones (Scheme 2) yields ctT-glycidic esters (28) with high geometric and diastereofacial selectivity which can be explained in terms of both open-chain or non-chelated antiperiplanar transition state models for the initial aldol-type reaction the ketone approaches the Si-f ce of the Z-enolate such that the phenyl ring of the chiral auxiliary and the enolate portion are face-to-face. Aza-Darzens condensation reaction of iV-benzylideneaniline has also been studied. Kinetically controlled base-promoted lithiation of 3,3-diphenylpropiomesitylene results in Z enolate ratios in the range 94 6 (lithium diisopropylamide) to 50 50 (BuLi), depending on the choice of solvent and temperature. ... 

Base-promoted Knoevenagel condensation to give an alkylated arylacrylonitrile. 

The incorporation of two nonidentical chiral residues, each supporting C2 symmetry, into a mactocyclic poly ether affords a chiral crown compound with C2 symmetry provided its structure is constitutionally symmetrical. Thus, base-promoted reaction of the half-crown diol prepared from (5)-birraphthol with the half-crown ditosylate d-72 synthesized tom diacetone-manrritol affords (144) the 20-crown-6 derivative (S)-d-113 with C2 symmetry. When d-72 is condensed in like fashion with (/ 5)-binaphthol, then the diastereoisomeric 20-crown-6 derivative (/ )-d-114 can be separated chromatogiaphically tom (S)-d-113. In this matmer, (/ 5)-binaphthol is resolved by the carbohydrate unit during the synthesis. 

Stronger bases or acids promote the cyclization of the 1 1 adduct, 51, to pyrazines and, as was shown for the case of o-phenylenediamine, 1 equivalent or more of a strong acid both catalyzes and directs the course of the condensation by promoting the loss of ammonium ion. Strong acid catalysis is described in more detail in the following section (72JOC4136). 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

A summary of the in situ use of the azobenzene probases is given in Table 2. Apart from the generation of ylid, referred to above, the main applications have been for N- and C-alkylation of weak nitrogen and carbon acids, for the promotion of condensation and substitution reactions involving carbanions such as the cyano-methyl anion, for an interesting carboxylation reaction (entries 4 and 17), and for base-promoted cyclisations (entries 5 and 6). 

A myriad of types of fused-ring pyrimidines derived from thioureas have been reported in the literature. For example, Howard and Lindsey387 reported the [l,3]-dithiino[5,4-d]pyrimidine ring system 223, and other workers made the octahydrobenzo[6]thieno[2,3-d]pyrimidirie 224 in 90% yield.388 The formation of both of these products was via a base-promoted condensation of a thiourea with a carbethoxy group however, in the former case the reaction was intermolecular and in the latter, intramolecular. Other unusual fused systems of this type have... 

Reaction of N-substituted bromomethanesulfonamides with 2 equiv of potassium carbonate and an cr-haloketone, ester, or nitrile leads directly to the /3-sultams 187 substituted at the C-3 position by an EWG. This base-promoted condensation can be used with a-halo ketones, esters, and nitriles where a second Sn2 intramolecular displacement can operate in tandem fashion (Scheme 60). This domino alkylation sequence exhibits a reactivity order where ketone > nitrile > ester (Table 14). The process is particularly efficient when diethyl bromomalonate or 3-chloro-2-butanone are involved <2004CJC113>. 

Mechanism 22-6 Base-Promoted Halogenation 1054 Mechanism 22-7 Final Steps of the Haloform Reaction 1056 Mechanism 22-8 Acid-Catalyzed Alpha Halogenation 1058 22-6 Alpha Bromination of Acids The HVZ Reaction 1059 22-7 The Aldol Condensation of Ketones and Aldehydes 1060... 

Deprotonation of the /3-keto ester provides a driving force for the Claisen condensation. The deprotonation is strongly exothermic, making the overall reaction exothermic and driving the reaction to completion. Because the base is consumed in the deprotonation step, a full equivalent of base must be used, and the Claisen condensation is said to be base-promoted rather than base-catalyzed. After the reaction is complete, addition of dilute acid converts the enolate back to the /3-keto ester. 

Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto-EnolTautomerism 1047 Acid-Catalyzed Keto-EnolTautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Base promoted condensation of diketone 535 with ethyl formate, followed by acetylation, afforded the functionalized C 17-heptaquinane 5 77.432)... 

Other intriguing observations were the identification of relatively stable l-/-butyldimethylsilyM-methylbenzo[f]furan < 1996JA10766>, and the preparation of the stable benzo[4furan derivative 138 starting from dimethyl 3,4-furandicarboxylate and A -methyl succinimide via a base-promoted condensation reaction, as can be seen in Equation (114) <19%S1180>. 

This suggests that in the case that both intramolecular C- and 0-arylations are of geometrically equal possibility, the former preferentially takes place. The reaction of o-bromobenzaldehydes with dibenzylketones gives l,3-diaryl-2-naphthols that may be useful materials as bulky 0-ligands (Eq. 24) [62]. This cyclization involves palladium-catalyzed a-arylation and base-promoted dehy-drative condensation. Treatment of o-iodoanilines with ketones produces indole derivatives (Eq. 25) [63]. In this case, dehydrative condensation between the amino group and the carbonyl group occurs initially and the subsequent car-bopalladation (mechanism A) leads to the products. 

A 3-hydroxyaldehyde (or ketone) will undergo elimination under basic conditions if the double bond being formed is especially stable, e.g., conjugated with an aromatic system. Such eliminations can occur under the reaction conditions of the base-promoted aldol condensation. An example is the formation of 3-phenyl-2-butenal by an E2 elimination from 3-hydroxy-3-phenylbutanal. 

The ring contraction rearrangement of alicyclic a-diketones is much more valuable from the synthetic viewpoint e.g. equation 4). There are several routes available for the synthesis of a-diketones from monoketones. These include direct oxidation using selenium dioxide permanganate or osmium tetrox-ide addition across the double bond of an enone followed by base-promoted elimination of water bromi-nation to give the dibromo ketone followed by hydrolysis condensation with 4-nitroso-/V,/V-dimethylaniline followed by acidic hydrolysis — but there are many others. The bromination-hydrolysis route has been extensively studied by Wallach." The conversion of menthone into 1-hydroxy-... 

Ketene acetals. Homologation with protection of aldehydes is accomplished by a base-promoted condensation with (Et0)2CHP(0)Phj and elimination of Ph2P(0)OH. If asymmetric dihydroxylation is then applied to the enol ethers, chiral ethyl a-hydroxyalkanoates are obtained. 

For a student preparation of ninhydrin starting with the condensation of dimethyl phthalate with ethyl acetate, one of us developed a technique for powdering sodium which seemed safe for use by beginners. Whatever hazard remained was eliminated by Gruen and Norcross by using sodium hydride dispersion in place of powdered sodium. Their yield is better than that obtained with powdered sodium (36-72%). Both bases promote ester interchange to give the methyl ester enolate. 

The synthesis of coumarins by the base-promoted condensation of ethyl nitroacetate with salicylaldehydes has been applied to 4-formyl-5-hydroxy[2.2]paracyclophane which... 

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