Reductive cross-coupling compounds

It is known that electrochemical reduction of oximes in protic media occurs in two steps the N—O bond is first reduced to form an imine and the latter is then reduced to afford a primary amine1,29. Tallec has shown that the amine from oxime 33 can be trapped intramolecularly (equation 16)35. Interestingly, the SS diastereomer predominates the chiral pyrrolidine ring derivative serves to control the stereochemistry of formation of the new benzylic chiral center. Electrochemical reductive cross-coupling of O-methyl oximes with carbonyl compounds in isopropanol at a tin cathode affords adducts (equation 17) which can be reduced further to 2-amino alcohols36. In this fashion, menthone could... 

Mg-promoted Reductive Cross-coupling of a,) -unsaturated Carbonyl Compounds with Aldehydes or Acyl Chlorides... 

The highly promoted effect of HMPA on reactions of Sml2 was reported for the first time in 1986 by Inanaga et al. [38] for the reductive cross-coupling of carbonyl compounds with a, 3-unsaturated esters (Scheme 8). HMPA was used as a cosolvent with THF (ca. 5%). Enhancement of the coupling rates and yields were quite remarkable however, the diastereoselectivity was sometimes diminished in the presence of HMPA. 

The best results were obtained when HMPA (5 equiv) and dimethylamino ethanol (DMAE, 2 equiv) were used as additives. The authors also reported the reductive cross-coupling of 1,3-dioxolane with carbonyl compounds to yield a-hydroxy derivatives [24] the reaction was performed in the presence of HMPA (ca. 5% of the solvent) and was complete within 5 min at room temperature (Scheme 11). 

Inanaga et al. reported the use of a 37% aqueous solution of formaldehyde for the reductive cross-coupling of carbonyl compounds with a,(3-unsaturated esters with the Sml2/THF-H20 system [38] (Scheme 47). 

Amino alcohols." The treatment of a mixture of an imine and a carbonyl compound with LN causes reductive cross-coupling. 

Reductive cross-coupling of carbonyl compounds. The low-valent titanium species couples ketones to nitriles and carboxylic acid derivatives such as esters and acid chlorides. The products represent reductive acylation products of ketones. ... 

Initially, there is an oxidative addition of the eledrophile R -X to a Pd(0) complex to afford intermediate II. In the case of using a Pd(II) complex as precatalyst, a previous reduction step of Pd(II) to Pd(0) occurs, generating the true catalytic species. Transmetalation between R -Pd-X and the boronic add R B(OH)2 with the aid of bases leads to the formation of intermediate 12. Reductive elimination then gives the cross-coupled compound R -R and the Pd(0) spedes is regenerated, restarting the... 

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

Zhang et al. reported the use of densely functionalized molecules through Suzuki cross-coupling reactions [65]. This synthesis involves the reductive amination of mucaholic acids to form the unexpected lactone (e.g., 82). Compound 82 can then be reacted with phenylboronic acid (83) to form the 2,3-diaryl-a, /J-unsaluralcd-y-lactone 84 as outlined in Scheme 19 in a 78% yield. A similar procedure is outlined in the work of Beilina et al. [66]. 

It proceeds by the standard mechanism for cross-coupling reactions oxidative addition of Pd(0) to the C-I bond, transmetallation to give the C-Pd(II)-C compound, and reductive elimination. 

With palladium catalysts aromatic chlorides are rather unreactive, however, nickel is able to catalyze the reactions of these substrates, too. The water-soluble catalyst was generated in situ from the easily available [NiCl2(DPPE)] and an excess of TPPTS by reduction with Zn in mixtures of 1,4-dioxane and water. Although it had to be used in relatively large quantities (10 mol %), the resulting compound catalysed the cross-coupling... 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The overall mechanism is closely related to that of the other cross-coupling methods. The aryl halide or triflate reacts with the Pd(0) catalyst by oxidative addition. The organoboron compound serves as the source of the second organic group by transmetala-tion. The disubstituted Pd(II) intermediate then undergoes reductive elimination. It appears that either the oxidative addition or the transmetalation can be rate-determining, depending on reaction conditions.134 With boronic acids as reactants, base catalysis is normally required and is believed to involve the formation of the more reactive boronate anion.135... 

Knochel and co-workers developed the Ni(acac)3-catalyzed cross-coupling reaction between polyfunctional primary iodoalkanes and a variety of primary diorganozinc compounds in the presence of w-trifluoromethylstyrene as a promoter. " The addition of this unsaturated promoter is required in order to coordinate to the nickel center and remove electron density from the metal atom, to facilitate the reductive elimination step. " " The scope of the reaction is extended, when Ni(acac)2 is used in the presence of BU4NI and fluorostyrene (Scheme With these... 

An acyl-palladium complex might undergo a series of follow up reactions. Subsequent transmetalation and reductive elimination lead to the formation of a carbonyl compound. This process is also coined carbonylative coupling, referring to the cross-coupling reaction, which would take place in the absence of carbon monoxide under similar conditions (for more details see Chapter 2.4.). 

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