Nucleophilic carbenes, structure

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

However, iV-ammonium salts as well as the IV-imines possess further acidic hydrogen atoms. In 0.2 N NaOD, (V-aminopyridinium salts (14) exchanged their hydrogen atoms at the 2-, and 4-, and 6-positions for a D atom within the time the NMR spectra could be measured.17 For the 4-amino-s-triazolium salts (93) base catalysis is not needed for the hydrogen exchange.134 The ylid or nucleophilic carbene structures 94 and 95 are intermediates (see also Wanzlick135 and Quast and Hunig136) and can be intercepted by sulfur or ethyl acetoacetate.134... 

Schrock-type carbenes are nucleophilic alkylidene complexes formed by coordination of strong donor ligands such as alkyl or cyclopentadienyl with no 7T-acceptor ligand to metals in high oxidation states. The nucleophilic carbene complexes show Wittig s ylide-type reactivity and it has been discussed whether the structures may be considered as ylides. A tantalum Schrock-type carbene complex was synthesized by deprotonation of a metal alkyl group [38] (Scheme 7). 

Although we are not specifically concerned here with kpp and the kinedcs of carbene-pyridine ylide formation, we note that the magnitude of is directly related to the structure and reactivity of the carbene. fcpyr ranges from 105 M s-1 for ambiphilic alkoxycarbenes to 109-10I° M-1 s 1 for electrophilic halocarbenes or alkylcarbenes. Very nucleophilic carbenes (MeOCOMe) do not react with pyridine.13... 

The ring system 24 especially exemplifies a nucleophilic carbene, since, as Breslow showed already more than 40 years ago,47 it is the structural element that is responsible for the activity of vitamin Bi48... 

Nucleophilic carbene 4 (R = Me, R = H) has been shown to disrupt the polymeric structure of beryllium dichloride to form an ionic carbene complex, 10 (15). The crystal structure of 10 revealed that the cation possesses a distorted tetrahedral coordination geometry at the beryllium center. The average Be-Cl bond distance (2.083(7) A) is... 

Irradiation of matrix-isolated imidazole-2-carboxylic acid gave the 2,3-dihydro-imidazol-2-ylidene-C02 complex (31) characterized by IR spectroscopy and calculated to lie 15.9 kcal mol above the starting material. A series of non-aromatic nucleophilic carbenes (32) were prepared by desulfurization of the corresponding thiones by molten potassium in boiling THF. The most hindered of the series (32 R = Bu) is stable indefinitely under exclusion of air and water and can be distilled without decomposition. The less hindered carbenes slowly dimerize to the corresponding alkenes. Stable aminoxy- and aminothiocarbenes (33 X = O, S) were prepared by deprotonation of iminium salts with lithium amide bases. The carbene carbon resonance appears at 260-297 ppm in the NMR spectrum and an X-ray structure determination of an aminooxycarbene indicated that electron donation from the nitrogen is more important than that from oxygen. These carbenes do not dimerize. 

Especially the report of the successful isolation of a stable carbene by Ar-duengo [6,7] (Scheme 1) and the publication of the solid-state structure of a stable imidazole-2-ylidene in 1991 led to a renaissance of these nucleophilic carbenes, which certainly also had an influence on the 2005 Nobel price in chemistry ... 

In the thiazolium cation the proton in the 2-position is acidic and its removal gives rise to the ylide/carbene 227. This nucleophilic carbene 227 can add, e.g., to an aldehyde to produce the cationic primary addition product 228. The latter, again via C-deprotonation, affords the enamine-like structure 229. Nucleophilic addition of 229 to either an aldehyde or a Michael-acceptor affords compound(s) 230. The catalytic cycle is completed by deprotonation and elimination of the carbene 227. Strictly speaking, the thiazolium salts (and the 1,2,4-triazolium salts discussed below) are thus not the actual catalysts but pre-catalysts that provide the catalytically active nucleophilic carbenes under the reaction conditions used. This mechanism of action of thiamine was first formulated by Breslow [234] and applies to the benzoin and Stetter-reactions catalyzed by thiazolium salts [235-237] and to those... 

In cooperation with Teles and colleagues, our research group has studied the triazole heterocycle as an alternative core structure of nucleophilic carbenes. First, the triazol-5-ylidene 12 (Fig. 9.3 see also Scheme 9.2) was synthesized and shown to be stable at temperatures up to 150 °C in the absence of air and moisture [22]. Compound 12 exhibited the typical behavior of a nucleophilic N-heterocyclic car-bene, and was found to be sufficiently stable to become the first commercially available carbene [23]. As shown in Scheme 9.2, the crystalline carbene was obtained from the corresponding triazolium salt precursor 13 by the addition of methanolate and subsequent thermal decomposition of the adduct 14 in vacuo via a-elimination of methanol [24]. 

I have been pursuing enzyme mimics, artificial enzymes that perform biomimetic chemistry, since starting my independent career in 1956. In the first work [52-59] my co-workers and I studied models for the function of thiamine pyrophosphate 1 as a coenzyme in enzymes such as carboxylase. We discovered the mechanism by which it acts, by forming an anion 2 that we also described as a stabilized carbene, one of its resonance forms. We examined the related anions from imidazolium cations and oxazolium cations, which produce anions 3 and 4 that can also be described as nucleophilic carbenes. We were able to explain the structure-activity relationships in this series, and the reasons why the thiazolium ring is best suited to act as a biological... 

Metal-based nucleophiles may react with activated haloarenechromium complexes leading to substitution of the halides. The reaction of Collmarfs reagent Na2[Fe(CO)4] with chloro-arenetricarbonylchromium complexes in THF/N-methylpyrrolidinone produces the yellow anionic dinuclear complexes 91a in 45 % yield (Scheme 40) as a result of an ipso SNAr [64]. Spectroscopic data suggest that complex 91a adopts the rj6 structure as opposed to the alternative //5 -cyclohexadieny 1 carbene structure 92. Similarly, it has been reported by the same group that the potassium salt of [CpFe(CO)2] participates in ipso nucleophilic attack on chloroarenechromium substrates, producing dinuclear complexes 91b in 92 % yield (Scheme 40) [65]. 

The formation of the observed products can be explained by the following catalytic cycle (Scheme 8). Addition of the nucleophilic carbene leads to adduct I, followed by proton transfer to give conjugate enamine Ha. Homoenolate equivalent Ha (see also resonance structure lib) can add to the aldehyde reaction partner providing zwitterion III and after... 

The synthesis and characterization of Et2Zn adducts with nucleophilic carbenes see Carbene Complexes) have been described. They are directly available and in good yields from a smooth reaction between Et2Zn and stable carbenes see Carbene Complexes) such as l,3-dimesityhmidazol-2-yhdene or l,3-di(l-adamantyl)imidazol-2-ylidene (equation 13). The solid-state structure of [Et2Zn l,3-di(l-adamantyl)imidazol-2-ylidene ] shows a zinc atom in a rather unusual trigonal planar arrangement, certainly due to a steric... 

The reaction of polymeric beryllium chloride (BeCl2) with nucleophilic carbene (1) (R = Me, R = H) is reported (equation 2) to yield a cationic carbene complex (10). The structure of the cation in (10) consists of the beryllimn center adopting a distorted tetrahedral coordination. Although... 

The nucleophilic carbene (112) has been shown to react with pnicogen pentafluorides (113a-c) to form adducts (114ac) with octahedral geometry at P (P N = 1.898 A), As (As-N = 1.999 A) and Sb (Sb-N = 2.175 A). The structures are therefore those of internal zwitterions with an imidazolium cation and a pnictogen anion. The strong nature of the bonds to the carbene... 

The reaction has to be carried out in the absence of oxygen and water, otherwise the intermediately formed nucleophilic carbene is oxidized to the tria-zolinone or suffers hydrolysis with subsequent aminal-type ring opening. Attempts to apply catalyst 7 to the synthesis of aliphatic acyloins gave very low yields and low enantioselectivities. Optimization of the catalyst structure with regard to activity and enantioselectivity yielded triazolium salt 8 as the best-suited system for the condensation of aliphatic aldehydes (Scheme 5) [37]. However, the enantiomeric excesses obtained, only up to 26%, and the rather low total turnover numbers, ranging from 4 to 8, are modest and a search for new, more active catalyst systems is highly desirable. 

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