Enamines oxidative coupling

When an oxidative coupling or addition takes place in the presence of carbon monoxide, CO insertion occurs leading to ketones. The Ru3(CO)12-catalyzed reaction of alkenylpyridyl or Af-(2-pyridyl)enamines and ethene performed under an atmosphere of carbon monoxide leads to the selective formation of a,/3-unsaturated ketones [16] (Eq. 11). After activation of the vinyl C-H bond, insertion of both carbon monoxide and ethylene takes place to give 25. 

An application of oxidative coupling of enamines to the synthesis of bichromones is also reported98 (Scheme 71). 

Very little is known about the chemistry of later steps of in vitro phaeomelanogenesis beyond the benzothiazine stage. Radiotracer studies (160) and model experiments (161) suggest that the alanyl side chain of the postulated intermediates does not take part in the polymerization process, which probably proceeds via an enamine-imine type condensation of the 1,4-thiazine ring system rather than by oxidative coupling at positions 2 and 8 and subsequent ring closure of the alanyl side chain as previously suggested by Minale et al. (162,163). 

At about the same time, Nicolaou and Chen et al. independently reported the synthesis of haplophytine [85]. Retrosynthetically, haplophytine was envisioned by a sequence of Suzuki-Miyaura Coupling, Vilsmeier-Haack reaction, and radical cyclization from indole 205 and vinyl iodide 206. The left-hand domain 205 could arise through the oxidative skeletal rearrangement of enamine 207, which could be obtained from the oxidative coupling of tetrahydro-jS-carboline 208 and diphenol 209 (Scheme 37). 

Attempts to use any other carbonyl compounds in this process led to either trace amounts of indole or no reaction at aU. That is why an alternative two-step, one-pot procedure utilizing p-ketoesters was explored. Similarly to the method originally discovered by Glorious and coworkers (08AGE7230), SFs-anilines 11 and 39 were first condensed with P-ketoesters in the presence of InBr3 under solvent free conditions, and the in situ formed enamine carboxylates then underwent subsequent cyclization by Pd-catalyzed, intramolecular oxidative coupling to give 2-methyl-3-carbalkoxy-5(6)-SF5-indoles (42a—h) in 40—46% yields (Scheme 10). 

Yasu Y, Koike T, Akita M (2012) Sunlight-driven synthesis of y-diketones via oxidative coupling of enamines with silyl enol ethers catalyzed by [Ru(bpy)3]. Chem Commun 48 5355-5357... 

SCHEME 22.21 Intramolecular oxidative coupling of A-aryl enamines. 

Scheme 11.29 The various pathways available to SOMO activation-type oxidative couplings in which it is the enamine that is oxidized.

Several new methods for oxidative coupling of enolates, enol silanes, and enamines have been reviewed and illustrated with reference to natural product synthesis. Copper(II)-catalysed oxidative cross-coupling of aldehydes and alkylbenzenes, to form benzyl esters on reaction with t-BuOOH, has been demonstrated. ... 

This new impurity proved to be derived from the Pd-catalyzed oxidation of DIPA to the enamine via P-hydride elimination. In fact, mixing Pd(OAc)2 with DIPA in DMF-d7 readily formed Pd black along with two species, primary amine and acetone, presumably derived from the enamine through hydrolysis. The resulting enamine or acetone then underwent a coupling reaction with iodoaniline 28. Heterocyclization through the arylpalladium(II) species provided 2-methyl indole 71, as shown in Scheme 4.19. 

An oxidative radical coupling promoted by tetra-ra-butylammonium cerium(IV) nitrate (TB ACN) between P-aminocinnamate 22 and enamine 23 provided pyrrole-3,4-dicarboxylate 24 <06T2235>. Dimerization of the P-aminocinnamates provided symmetrical pyrroles. 

For a synthesis of leurosidine (56), 15,20-dihydrocatharanthine iV-oxide (57) was subjected to coupling with vindoline (3) under the modified Polo-novski conditions. The initial adduct, imonium salt 58, was converted to the enamine 59 in base. Oxidation of this product with osmium tetrox-ide proceeded chemo- and stereoselectively, without reaction of the... 

The relatively facile formation of anhydrovinblastine (42) by the modified Polonovski reaction, and the poor yields experienced on coupling of other catharanthine derivatives, made anhydrovinblastine an attractive precursor for the preparation of additional binary alkaloids, including vinblastine itself (50,57). Hydrogenation to 20 -deoxyleurosidine (61a), formation of its Af -oxide (78), and reaction with trifluoroacetic anhydride led to the enamine 59 (Scheme 23). Oxidation of this enamine with thal-... 

Fritsch and Weingarten 386 have studied the electrooxidation of 22 substituted enamines by cyclic voltammetry and ESR spectroscopy. Oxidation potentials of these strong electron donors may be as low as -0,901 V (vs.S.C.E.). The life times of the initially formed radical cations range from 0,005 sec to days depending on the efficiency of reactive site blocking or stabilization by substituents. Coupling constants from the ESR spectra indicate that the unpaired electron is polarized away from the dimethylamino substituents. The opposite is true for the... 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

In the case of the enaminonitrile XVIIa, coupling through the phenyl ring is observed [127a]. Enamines related to the key intermediate in thiamine diphosphate-dependent enzymatic pathways lead to dimers in a one-electron oxidation via a thiazolium cation radical as intermediate [127b]. Anodic oxidation of enaminones, prepared from / -substituted acetophenones and A,A-dimethylformamide dimethylacetal, afford dimers and substituted furans in fair yield [127c]. 

Evidence for oxidative metabolism of the endocyclic enamines has been obtained for both 1-BP and PCP. In a previously reported (Masumoto et al. 1991) preparative scale metabolism of 1-BP, it was found that in addition to the C -C. coupled dimer 3, small amounts of l-benzyl-3- piperidol (l-BP-3-ol), l-benzyl-4-piperidol (l-BP-4-ol), and 1-benzyl-3-piperidone (l-BP-3-one) were obtained (figure 5). It was further found that cyanide reduced greatly the levels of l-BP-3-one metabolite but not the l-BP-3-ol metabolite, suggesting that 1-BP-3-one is generated principally from the initial metabolite (1-BP-Im ) rather than from oxidation of l-BP-3-ol (Masumoto et al. 1991 Sayre et al. 1991). Consistent with this notion is the finding of relatively large amounts of the corresponding 3-one in the... 

Enamines, e.g. (67), rve as oxidizing agents in the coupling of PH-spirophos-phoranes with alcohols to give alkoxyspirophosphoranes, e.g. (68), and in the oxidation of the phosphonites (69) to spirophosphoranes. ... 

Oxidation of N-alkyl or A -aryl enamines, with a secondary nitrogen, can lead to poor to modest yields of ligand coupling products or their products of imine hydrolysis. Mixtures of dimeric... 

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