Esters intermolecular reactions

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

Gong and co-workers employed an intermolecular Nenitzescu reaction, a type lice transformation, for the condensation of a P-amino-a,(3-unsaturated ester with 1,4-benzoquinone to afford a 5-hydroxyindole derivative <06BMC911>. 

Thermo Fisher). The small cross-bridge, built from a benzoic acid group, provides crosslinking ability at short intermolecular distances. Reaction of one protein via the NHS ester end of the crosslinker provides a stable derivative that can be incubated with a target molecule and then photolyzed to effect the final conjugation (Figure 5.20). 

Scheme 5.3 (a) Mechanism of ester and anilide ethanolysis catalyzed by dinuclear complexes, showing productive (II) and non-productive (I and III) species and (b) the corresponding intermolecular model reaction based on monomolecular complexes. 

When the diazoesters (240) and (241) were thermally decomposed in the presence of copper(II) acetoacetate ester as catalyst, an intermolecular carbene reaction occurred, the resulting benzo[c]furans (242) and (243) were not isolated but were trapped as the Diels-Alder adducts with N- methylmaleimide and dimethyl acetylenedicarboxylate (76CL287). 

Quaternary ammonium hydroxides anchored on MCM-41 provide stronger base catalysts than amine analogues11731 and were able to catalyse the same reaction as previously reported namely for the intermolecular Michael reaction leading to flavanone.[181] Moreover, this catalyst induced the successive intramolecular olefinic attack of the phenolic group from the Knoevenagel condensation product of salicylaldehyde and diethyl glutaconate (Scheme 9.6). This fast cyclization leads to chromene derivatives (1) from which subsequent conversions induced by proton abstraction from the alpha position of the ester function gives coumarin... 

Intermolecular addition reaction is important. Generally, alkyl radicals derived from O-acyl esters (2) are nucleophilic, so treatment with electron-deficient olefins such as... 

Dirhodium(II) tetrakis(carboxamides), constructed with chiral 2-pyrroli-done-5-carboxylate esters so that the two nitrogen donor atoms on each rhodium are in a cis arrangement, represent a new class of chiral catalysts with broad applicability to enantioselective metal carbene transformations. Enantiomeric excesses greater than 90% have been achieved in intramolecular cyclopropanation reactions of allyl diazoacetates. In intermolecular cyclopropanation reactions with monosubsti-tuted olefins, the cis-disubstituted cyclopropane is formed with a higher enantiomeric excess than the trans isomer, and for cyclopropenation of 1-alkynes extraordinary selectivity has been achieved. Carbon-hydro-gen insertion reactions of diazoacetate esters that result in substituted y-butyrolactones occur in high yield and with enantiomeric excess as high as 90% with the use of these catalysts. Their design affords stabilization of the intermediate metal carbene and orientation of the carbene substituents for selectivity enhancement. 

Intermolecular cyclopropanation reactions with ethyl diazoacetate have been employed for the construction of the cyclopropane-containing amino acid 7 (equation 25) Thus, rhodium(II) acetate catalysed decomposition of ethyl diazoacetate in the presence of d-cbz-vinylglycine methyl ester 5 afforded cyclopropyl ester 6 in 85% yield. Removal of the protecting group completed the synthesis of 7. Another example illustrating intermolecular cyclopropanation can be found in Piers and Moss synthesis of ( )-quadrone 8" (equation 26). Intermolecular cyclopropanation of enamide or vinyl ether functions using ethyl diazoacetate has also been used in the synthesis of eburnamonine 9", pentalenolactone E ester 10" and ( )-dicranenone A11" (equations 27-29). 

Caddick [19] has reported the use of a novel polymer-supported tetra-fluorophenol-Unked acrylate as an activated acceptor for intermolecular radical reactions. Treatment of immobiUzed acrylate 132 with a variety of alkyl iodides in the presence of tributyltin hydride and AIBN gave the corresponding esters 133 (Scheme 29). NucleophiUc cleavage using amines gave amides 134 in good overall yield whilst regenerating phenol resin 131. 

Dirhodium(II) catalysts that possess chiral 2-pyrrolidone-5-carboxylate ester ligands (mepy) are the most effective among those of dirhodium or copper for highly diastereoselective and enantioselective intermolecular cyclopropenation reactions between l-alkynes and diazoesters (eq. (9)). Product yields are moderate, and enantiomeric excesses range from 40 to 98 %. Interestingly, the (R) or (5) catalyst produces the cyclopropene-l-carboxylate respectively with the (/ ) or (5) configuration [26]. 

Unlike intermolecular cyclopropanation reactions, the intramolecular version is stereo-specific with respect to the configuration of both, the C-C double bond and (due to steric constraints) the carbenoid center. This fact can be used for the directed synthesis of cis-1,2-disubstituted, all-ci. -l,2,3-trisubstituted or d. , ra . -l,2,3-trisubstituted cyclopropanes. For example, a-diazo esters (a-diazocarboxamides) with an unsaturated ester (amide) residue yield bicyclic lactones (lactams) stereospecifically which can be ring opened to give the monocyclic cyclopropanes mentioned with defined stereochemistry. Some possibilities are illustrated by the examples, 20 -+ 22 -> 23, and 24 25. ... 

The WWD is broader than expected for a "living" polymer, especially in the case of the Hi,-furan systems. This can be expected on the basis of the reaction between active chain ends and ester groups in the polymer chain, l.e., intramolecular and Intermolecular ester interchange. This reaction also leads to marked degradation when the active chain ends are kept for longer period of time (see Table I). 

Dirhodium tetracarboxylate complexes are among the most successful and well-studied catalysts for C-H amination. Early work by Miiller provided support for a concerted asynchronous reaction mechanism for intermolecular amination reactions using Rh2(OAc)4 and NsN=IPh [22-24]. Du Bois and coworkers have shown that carbamate and sulfamate esters can engage in oxidative cyclization reactions promoted by these same types of Rh complexes using PhI(OAc)2 as the terminal oxidant [93-96]. Mechanistic studies, which include Hammett analysis (p = 0.55... 

Several studies have focussed on the use of chiral esters as auxiliary groups in radical transformations. Perhaps the most comprehensive survey of auxiliary groups was reported by Snider and collaborators in their pioneering examination of Mn(llI)-promoted radical cyclization reactions of fi keto amides and esters [34]. The selectivities obtained in cyclization generally mirror those observed in inter-molecular addition reactions. These examples again illustrate that the models developed for intermolecular radical reactions can apparently be applied successfully to intramolecular additions (cyclizations). Selectivity for the conversion of 34 to 35... 

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