Amides carbonyl olefination

First, solvent molecules, referred to as S in the catalyst precursor, are displaced by the olefinic substrate to form a chelated Rh complex in which the olefinic bond and the amide carbonyl oxygen interact with the Rh(I) center (rate constant k ). Hydrogen then oxidatively adds to the metal, forming the Rh(III) dihydride intermediate (rate constant kj). This is the rate-limiting step under normal conditions. One hydride on the metal is then transferred to the coordinated olefinic bond to form a five-membered chelated alkyl-Rh(III) intermediate (rate constant k3). Finally, reductive elimination of the product from the complex (rate constant k4) completes the catalytic cycle. 

Nair et al. (87,88) achieved a synthesis of spirooxindole-containing molecules by adding isatins to various carbonyl ylides (Scheme 4.46). There has been relatively little research regarding the efficiency of C=0 of 1,2-dicarbonyl compounds as dipolarophiles relative to their olefinic counterparts. As anticipated, Nair found that the more electrophilic carbonyl of the isatin 187 (non-amide carbonyl) reacted smoothly with the carbonyl ylide formed from diazoketone 186 to give the spirocyclic adduct 188. Nair s yields were moderate to good (44—83%), but were based on recovered isatin. 

Watanabe et al. reported that the addition of C-H bonds in aldehydes to olefins took place efficiently with the aid of Ru3(CO)12 under a CO atmosphere at 200°C (Eq. 51) [118]. They also reported that the same ruthenium-carbonyl complex catalyzes the addition of the C-H bonds in formic acid esters and amides to olefins (Eq. 52) [119]. 

Biologically active molecules containing amide bonds suffer usually of pharmacokinetic liability. In order to increase their stability, bioisosteric transformation of the carboxamide have been performed and yielded a lot of successful examples especially in the area of petidomimetic. The isosteric replacements for peptidic bonds have been summarized by Spatola and by Fauchere. " The most used and well-established modihcations are iV-methylation, configuration change (o-conhguration at Ca), formation of a retroamide or an a-azapeptide, use of aminoisobutyric or dehydroamino acids, replacement of the amidic bond by an ester [depsipeptide], ketomethylene, hydroxyethyl-ene or thioamide functional group, carba replacement of the amidic carbonyl, and use of an olefinic double bond (Figure 15.33). 

Enamides are successful substrates on account of their closely defined coordination geometry, since both the olefin and amide carbonyl group are available to bind at c/s-related sites. This must be necessary during the rate-determining stage, for species lacking the amide group (or a closely related functionality similarly sited) react much more slowly and with lower stereoselectivity. 

The olefination reaction took place chemoselectively at the amide carbonyl to give corresponding enamides 45. The RCM step was performed using Grubbs second-generation catalyst 3 in toluene either at 80 °C or at reflux. Unfortunately, in this case, formation of 2,3-disubstituted indoles was not observed probably owing to steric effects the results are summarized in Table 3. 

PPV (27a) has been prepared by a number of different methods which were studied in detail by Horhold and Opfermann [129]. It can be synthesized by bifunctional carbonyl olefination of terephthalaldehyde according to Wittig s reaction and from /)-xylylene-bis-(diethyl phosphonate) as well as by dehydrochlorination of p-xylylene dichloride with sodium hydride in N,N-dimethylformamide and with potassium amide in liquid ammonia. Another route to PPV used today is the precursor route, first described by Wessling [130 133] and Kanabe [134], starting from the monomers /)-xylylene-bis(dimethylsulfo-nium tetrafluoroborate) [134] or chloride (Scheme 28) [130-133],... 

Carbonyl Olefination with Titanocene-Methylidene and Related Reagents 157 Tab. 4.4. Methylenation of amides, imides, and thiol esters with the Tebbe reagent 3. 

PPV (62a) has been prepared by a number of different methods which were studied in detail by Horhold and Opfermann [390]. It can be synthesized by bifunctional carbonyl olefination of terephthalaldehyde according to Wittig s reaction and from />-xylylene-bis(diethyl phosphonate), as well as by dehydrochlorination of/p-xylylene dichloride with sodium hydride in A jiV-dimethylformamide and with potassium amide in liquid ammonia. The most popular route to PPV used today is the precursor route, first described by Wessling and Zimmermann [391-394] and Kanabe and Okawara [395], starting from the monomers p-xylylene-bis(di-methylsulphonium tetrafluoroborate) [395] or chloride (Scheme 11.17) [391-394]. The latter is polymerized to yield a water soluble sulphonium salt polyelectrolyte (63d) which is then purified by dialysis [396]. The precursor polymer is converted to PPV (63e) by the thermal elimination of dimethyl sulphide and HCl. The method was later developed by Horhold et al. [397], Lenz and co-workers [398,399], Murase et al. [400] and Bradley [401], One of the major improvements within the last years has been the use of tetrahydrothio-phene instead of dimethyl sulphide in the synthesis of the precursor polymer [402]. The use of the cyclic leaving group facilitates the elimination when the precursor polymers is heated at 230-300°C and leads... 

Study of the aliphatic portion of rifamycin S commenced with the observation that it contains an a-methyldienamide. This follows from comparison of the ultraviolet spectra of rifamycin S and tetrahydro-rifamycin S (Fig. 15), which showed that the amide carbonyl was conjugated with two double bonds, and from characterization of (19), whose ultraviolet spectrum was that of a methyl dienoate and whose proton magnetic resonance spectrum showed olefinic protons at C-3, C-4 and C-5. Products isolated from the vigorous oxidation of tetrahydrorifamy-cin S (Fig. 15) indicated the substitution pattern of the aliphatic bridge... 

While the usual eonsequence of hydration of enamines is eleavage to a secondary amine and an aldehyde or ketone, numerous cases of stable carbinolamines are known (102), particularly in examples derived from cyclic enamines. The selective terminal hydration (505) of a cross-conjugated dienamine-vinylogous amide is an interesting example which gives an indication of the increased stabilization of the vinylogous amide as compared to simple enamines, which is also seen in the decreased nucleophilicity of the conjugated amino olefin-carbonyl system. 

TV-Substituted amides and lactams possess potentially reactive C—H bonds on carbon atoms alpha to the nitrogen and carbonyl group. These hydrogen atoms are easily abstracted by excited carbonyl compounds (e.g., acetone or benzophenone) to produce radicals which undergo olefin addition <9a,98 97) ... 

Low-coordinate species of the main group elements of the second row such as carbenes, olefins, carbonyl compounds (ketones, aldehydes, esters, amides, etc.), aromatic compounds, and azo compounds play very important roles in organic chemistry. Although extensive studies have been devoted to these species not only from the physical organic point of view but also from the standpoints of synthetic chemistry and materials science, the heavier element homologues of these low-coordinate species have been postulated in many reactions only as reactive intermediates, and their chemistry has been undeveloped most probably due to... 

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