Bromo enamides

Hence, in parallel with the above studies, hydrogenations of substrates lacking the nitrile group were explored with two possibilities being considered-use of the related bromo-enamide, and temporary protection of the nitrile group during the hydrogenation step. 

It initially appeared that it should be feasible to carry out the asymmetric hydrogenation using bromo-enamide 39 and to introduce the nitrile group as the final chemical transformation (Scheme 9.29). 

Scheme 9.30 Complications encountered during synthesis of bromo-enamide 39.

Scheme 83 Synthesis of P-lactams by bromo-enamides radical cyclization...

Bromo-enamides have been reported to give radical cyclization in excellent yields (82-99%) to p-lactams using catalytic amounts (30%) of tripyridylamine (TPA) copper halide complex [184]. The p-lactam developed under mild conditions via 4-exo bromine atom transfer and subsequent elimination of the tertiary bromide that could be readily achieved by reaction with DBU (Scheme 83). 

Disubstituted protoberberines have been synthesized in high yield by the photolysis of the related bromo-enamides (Scheme 3). The enamide (75) is converted into the enamide (76) in 80% yield by photolysis, and the cyclized base can... 

Further investigations on the influence of the substituents on the terminal carbon of the olefin were reported by Ikeda and coworkers [26] employing the bromo enamides 96 as substrates. These studies revealed that two thiophenyl groups on the terminal olefinic carbon accelerate the 4-exo trig cyclization to synthetically useful levels. Subsequently, these reactions were applied in the total syntheses of the P-lactam antibiotics PS-5 and thienamycins first in racemic form and later in optically active forms, employing (x-phenylethylamine as the chiral auxiliary. 

The Pummerer rearrangement has been employed in tandem with other reactions to enable complex transformations to be carried out efficiently and in a one-pot manner. Studies of these have been reported mainly by Padwa who has utilized such transformations in the syntheses of natural products. A particularly intriguing cascade sequence involving the Pummerer rearrangement was employed in the synthesis of the alkaloid jamtine, 57. " Padwa et al. synthesized the bromo-enamide 55 in a 4 1 (Z/ ) mixture of isomers. Treatment of the isomeric mixture with camphorsulfonic acid caused the the sulfoxide to undergo a Pummerer/Mannich ion cyclization, which was then followed by a spontaneous Pictet-Spengler reaction to furnish the isoquinoline core. Although a 5 2 1 1 mixture of diastereoisomers was obtained, the desired diastereoisomer 56 was formed preferentially. This was attributed to a 4 r-Nazarov-type conrotatory electrocyclisation which controls the direction of closure from the a-acylthionium ion intermediate. 

The corresponding reaction of the isomeric enamide (79) is more complex. Photolysis of this compound in methanol gives the partially demethylated cycliza-tion product (82), with the expected substitution pattern, in 65% yield, together with the desmethoxy-compound (81 R = H) (20%). In benzene, the main product of photolysis is the desmethoxy-bromo-compound (81 R = Br). The mechanism of the cyclization with loss of a methoxy-group may be represented as in structures... 

Regiochemistry of enamide photocyclization in this synthesis can also be controlled by the use of an ortho substituent that acts as an eliminating group on cyclization to the root of the substituent. Thus, the omethoxyl and bromo groups are used for this regioselective cyclization as exemplified by a number of total syntheses of alkaloids (19,20) (Scheme 37). 

Dicentrine and Dicentrinone. Dicentrine (283) was synthesized by photo-cyclization of the o-bromo- and chloroenamides 282a and b by Cava et al. (138) the former enamide (282a) was best suited for the synthesis of the alkaloids in view of yield and reaction time (Scheme 103). 

Asymmetric hydrogenation of bromo-substituted aromatic a-enamides 14 affords the corresponding bromo-amino acid derivatives 15, which subsequently is subjected to Pd-catalyzed cross-coupling with aryl and vinyl boronic acids. In addition to diverse phenylalanine derivatives 16, a broad array of other novel aromatic and heterocyclic amino acids have been produced rapidly from a small number of bromo-functionalized intermediates [24], This same two-step process may be applied to the production of many other classes of aromatic and heterocyclic chiral building blocks, such as arylalkylamines, amino alcohols, diamines, and directly on peptides as well. 

The tricyclic /3-aminocyclohexenone 234 was obtained via intramolecular photoarylation of the bromo arene derivative 233 (Scheme 40). Enamide 234 was treated with sodium hydride, followed by the mesylate derivative of [(trimethylsilyl)methyl]allyl alcohol, to give the allylated compound 235, which was converted to two allyliminium salts 236 and 237. However, attempts to photocyclize these compounds to tetracyclic derivatives were not successful, in contrast to the results of the earlier studies (Scheme 35) in which the spirocyclic system was easily generated in intermediates not rigidly tethered to the aromatic ring. 

The aziridination of electron-deficient alkenes can be carried out under slightly different conditions. The reaction between primary amines 143 and 2-bromo-2-(cycloalkylidene)-acetates 144 in alcohol under high pressure provides spiroaziridines 145 in good yields and diastereomeric excesses. The reaction is general for most primary amines, except for those that are weakly nucleophilic or sterically bulky <01EJOC2569>. Enamides (e.g., 147) can be... 

Diacetoxyiodo)benzene in combination with simple bromide salts in ethanol can be used for the regios-elective ethoxybromination of a wide range of enamides, giving synthetically versatile a-bromo hemi-aminals [98]. 

Kororamide A (141) was isolated from Australian bryozoan Amathia tortuosa by Carroll et al. (Figure 11) [68]. The structure was determined by extensive NMR spectroscopic techniques and it was assigned as 2,6,7-tri-bromo substituted indole ring coimected to a proline moiety through Z-enamide functionality. 

When we tested the Heck conditions [212] with iodo indole III-79Boc, only complex mixture of product was observed and no traces of the desired enamide III-96 were present (Scheme 4.73). On the other hand, in the case of bromo indole... 

Using the Fu conditions, no reaction was observed at room temperature, neither with bromo indole III-94 nor chloro indole III-95 [216]. However, in the case of bromo indole III-94, the reaction was done at 80 °C and the a-enamide III-98 was formed in a 10 % yield. Alternatively, with A-Boc chloro indole III-95, a mixture of a-enamide III-98 and /1-enamide III-96 was detected in a 7 and 16 % yield (Scheme 4.74). 

Until now, most of the palladium-catalyzed carbonylation of C-H bonds preferentially proceeds under the acidic conditions which may favor the generation of the cationic Pd(II) species and inhibition of the possible reduction of Pd(II) to Pd(0) by CO. But this procedure runs under basic conditions (in DMF with basic DABCO and KI as the additive. Table 15.27). Many kinds of substituents on the aromatic ring of enamides were tolerated and especially the bromo and... 

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