Nickel enolates

The course of the reductive carbonylation reaction is considered to involve intially the alkoxycarbonyl complex 156, which attacks 150 to form the nickel enolates 157 followed by protonation [81]. (Scheme 56)... 

It is supposed that the nickel enolate intermediate 157 reacts with electrophiles rather than with protons. The successful use of trimethylsilyl-sub-stituted amines (Scheme 57) permits a new carbon-carbon bond to be formed between 157 and electrophiles such as benzaldehyde and ethyl acrylate. The adduct 158 is obtained stereoselectively only by mixing nickel tetracarbonyl, the gem-dibromocyclopropane 150, dimethyl (trimethylsilyl) amine, and an electrophile [82]. gem-Functionalization on a cyclopropane ring carbon atom is attained in this four-component coupling reaction. Phenyl trimethyl silylsulfide serves as an excellent nucleophile to yield the thiol ester, which is in sharp contrast to the formation of a complicated product mixture starting from thiols instead of the silylsulfide [81]. (Scheme 58)... 

With dimethyl(trimethylsilyl)amine, the nickel enolate 162 is capable of reacting with benzaldehyde to produce the condensation product 163 (Scheme 60). 

Transition metals 172 a-bonded to cyclopropanes, substituted on the a-carbon with a halogen atom, are interesting intermediates for cyclopropylidene complexes 173 or allene ones 174 [88]. The former complexes are also supposed to be precursors of the above-mentioned nickel enolates. (Scheme 65)... 

The mechanism of epoxide formation (Scheme 7) has not been established but the intermediacy of nickel enolates and ensuing aldol type reactions are suspected28 (cf. Zn-mediated formation of furans from a-bromoketones29). A limitation on the synthesis is that R cannot be aryl for these cases, the products are 2,4-diarylfurans (see Section IV,B,1).30... 

Ligand-free catalysts have been prepared from the following types of nickel(II) compounds nickel salts of long-chain aliphatic or aromatic carboxylic acids (10, 11) or of sulfonic acids (11), nickel enolates of /3-diketones (11) [e.g., nickel acetylacetonate (4, 12)] or their imino derivatives (11, 13), nickel phenolates (11), dithiocarbamates (14), and mer-captides (15). 

Nickel-based Ziegler catalysts can be prepared using halogen-free or-ganoaluminum compounds of low Lewis acidity, e.g., dialkylaluminum alkoxides. However, the catalytic properties of these systems differ remarkably from those described above. The nickel components in such a case may be nickel acetylacetonate, or the nickel enolates of various other /3-dicarbonyl compounds (44, 45), in particular such halogenated /3-dicarbonyl compounds as hexafluoroacetylacetone (44, 46). 

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

Alkynyl enals cyclize on treatment with a stoichiometric amount of Ni(COD)2/TMEDA complex to give nickel enolates such as 193,436>436a These metallacycles react with electrophiles including methyl iodide and benzaldehyde to yield cyclopentenol derivatives (Scheme 91). 

Evans et al. reported enantioselective addition of achiral A-acylthiazolidinc thiones to C=0 electrophiles catalyzed by chiral nickel complexes 198 and 199 (Equations (84) and (85)).442 442a In situ generation of chiral nickel enolates in the presence of a base is proposed. 

Dibromocyclopropanes with vicinal chloromethoxy or mesyloxymethyl substituents undergo [Ni(CO)4]-induced ring opening-carbonylation in the presence of alcohol or amine, leading to y.S-un-saturated carboxylic acid derivatives selectively via intermediate nickel enolates (equation 115).262 Di-... 

Despite the toxicity of volatile metal carbonyls, particularly Ni(CO)4, several useful transformations have been developed employing these reagents. Monocarbonylation of gem-dibromocyclopropanes may be accomplished with Ni(CO)4 in the presence of alcohols, amines or (less successfully) thiols, to afford cyclopropane carboxylic esters, amides or thioesters, respectively (equation 202)400. Silylamine or silylsulfide reagents may take the place of amines or thiols401. The intermediacy of a nickel enolate in the carbonylations is... 

The synthesis of complex polycyclic molecules has been achieved by Montgomery et al. by cascade cyclization processes involving nickel enolates [40]. Up to three cycles could be generated in the intramolecular version of the reaction. Alkynyl enal or enone were first converted into their corresponding seven-membered cyclic enolates in the presence of Ni(cod)2/TMEDA [41 ]. These species could be trapped by electrophiles such as aldehydes. For example, upon treatment with the nickel catalyst, dialdehyde 32 afforded spiro-cycle 35 in 49% yield as a single diastereomer (Scheme 17). 

Scheme 17 Cascade cyclic nickel enolate formation/aldolization reaction...

Cascade Cyclizations and Couplings Involving Nickel Enolates... 

In addition, the synthesis of enolate complexes of nickel has been carried out by Campora and co-workers <2003CC1742, 2003JA1482>. Treatment of a THF solution of Ni(C6H4-o-C(0)CH3(Gl)(dippe) 106 with 1 equiv of KO/-Bu allowed the preparation of the nickel enolate 107 in good isolated yield (60%). O-Coordination of the enolate fragment could be proposed on the basis of the NMR spectra. Thus, the terminal methylene group gave rise... 

Synthesis ofp-epoxy ketones.20-21 Nickel carbonyl reacts with an a-bromo ketone (DMF, argon, 30°, 5 hrs.) to give a/3-epoxy ketone, for example (2). Yields are in the range 50-80%. The reaction is considered to proceed via an aldol-type condensation between the ketone and the nickel enolate followed by elimination of NiBr2. 

The dearest empirical evidence for the productive involvement of an 1] , O-bound nickel enolate comes from the intermolecular reductive coupling of alkynes and enals (Scheme 8.9) [27]. The extremely high levels of Z-isomer stereoselectivity (>98 2) can best be rationalized via the metallacycle intermediate 5 which undergoes o-bond metathesis to afford nickel hydride 6, followed by reductive eUmina-tion to yield the Z-selective enol silane product 7. A mechanism consisting of a nickel Jt-allyl species would not be expected to lead to high selectivities of Z-enol silanes, and has been imphcated in reactions leading to the selective production of T-enol silanes [28],... 

Recent studies have illustrated that both borane and silane reductants may be avoided entirely by the use of methanol as the stoichiometric reductant (Scheme 3-50). Deuterium labeling studies illustrated that the hydroxyl proton and a single methyl-derived proton from methanol are transferred to Ae observed reductive coupling product. The likely mechanistic pathway for this transformation involves metallacycle formation, followed by nickel enolate protonation by methanol to afford intermediate 23. p-Hydride elimination of the methoxy ligand extrudes formaldehyde and forms a nickel hydride intermediate that undergoes productforming reductive elimination. 

The only a-alkyl substrate (R = n-Pr, X = S) reacted with poor yield (15%) and enantioselectivity (11% ee). The unique combination of the catalytic components was specifically chosen to offer a dual activation of the substrate and reagent the formation of the activated nickel-enolate complex was assisted by the presence of the noncoordinating Bronsted base, while the Lewis acidic EtsSiOTf activated NFSI to become a stronger nucleophile, without interfering with the formation of the enolate. C-F bond formation resulted from the reaction between the activated substrate and the activated electrophile, prior to product release. 

The nickel-catalyzed reductive coupling reaction of methyl vinyl ketone with enyne 43 bearing a P-dicarbonyl moiety proceeds with liberation of the P-dicarbonyl enolate (Scheme 5.56) [39]. Reductive coupling of 43 with enone would afford nickelaoxacyclooctadiene 44. Transmetalation is accompanied by carbonickelation to yield 45. Intermediate 45 engages in P-carbon elimination through a six-membered cyclic transition state to liberate nickel enolate 46, which should be transformed to the corresponding zinc enolate to complete the catalytic cycle, and zinc enolate 47, which is eventually protonated upon hydrolysis. 

Reductive transformations are also achieved by using other low-valent metals, which permits the functionalization of gm-dihalocyclopropanes. For example, use of Ni(CO)4 as a reductant leads to reductive cabonylation of gm-dibromocyclopropanes via nickel enolates [46-50]. 

Transmetallation of the lithium or potassium enolates is also a reliable method for the preparation of palladium and nickel enolates, as illustrated in Scheme 2.50. Clear evidence for the C-bound structure of enolates 172 and 173 thus prepared was provided by NMR spectroscopy and - for nickel enolate 172 (M = Ni, L = Cp ) - by a crystal structure analysis. The reaction of C-bound nickel and palladium enolates 172 and 173 with aldehydes is much more sluggish and much less uniform than the analogs of that of the polar main-group metals. In addition to P-hydroxyketones or esters, products resulting from a Tishchenko reaction were also observed [164b]. 

Also in the enolates of group 10 metals, the different metalla tautomers were postulated, isolated, and characterized. Generally, it is assumed that in particular palladium - due to its low oxophilicity - favors the C-bound mode, but for this metal too, the O-bound tautomer has been detected. In an early study on nickel and palladium enolates 37, the C-bound structure was assigned on the basis of and C NMR and IR spectroscopy and confirmed for the nickel ester enolate (L = Cp, R = OCMe3) by a crystal structure [73]. The metallacyclic nickel enolates 38, on the other hand, are O-bound tautomers, as unambiguously shown by a crystal structure of the complex 38a, wherein the nickel adopts a slightly distorted square planar coordination. A slow equilibration was observed between the O-bound tautomer 38b and the C-bound isomer 39, with AG = 25.3 kcal mol . Remarkably, the isomerization rate was substantially... 

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