Electron-deficient carbene

Yet another kind of alkene addition is the reaction of a carbene with an alkene to yield a cyclopropane. A carbene, R2C , is a neutral molecule containing a divalent carbon with only six electrons in its valence shell. It is therefore highly reactive and is generated only as a reaction intermediate, rather than as an isolable molecule. Because they re electron-deficient, carbenes behave as electrophiles and react with nucieophiiic C=C bonds. The reaction occurs in a single step without intermediates. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

In the context of 12, the diazo keto function and the thiolactam are in proximity. This circumstance would seem to favor any process leading to the union of these two groupings. It is conceivable that decomposition of the diazo function in 12 with rhodium(n) acetate would furnish a transitory electron-deficient carbene which would be rapidly intercepted by the proximal thiolactam sulfur atom (see 20, Scheme 4). After spontaneous ring contraction of the... 

The reactivity of these carbene complexes can be understood as an electron-deficient carbene carbon atom due to the electron-attracting CO groups, while... 

High-valent, electron-deficient carbene complexes can either require activation (e.g. by a Lewis acid) to catalyze metathesis (Table 3.14) or not require any... 

Carbenes [74-76], and in particular W-heterocyclic carbenes (NHCs), are today the topics of very intense research [43 8]. Carbenes were originally considered as chemical curiosities before being introduced by Doering in organic chemistry in the 1950s [77], and by Fischer in organometallic chemistry in 1964 [5]. Eater, it was shown that the stability of carbenes could be dramatically enhanced by the presence of heteroatom substituents. After the discovery of the first stable carbene, a (phos-phino)(silyl)carbene, by Bertrand et al. in 1988 [78], a variety of stable acyclic and cyclic carbenes have been prepared. With the exception of bis(amino)cycloprope-nylidenes [79], all these carbenes feature at least one amino or phosphino group directly bonded to the electron-deficient carbenic center. 

In contrast to methylene, carbenes which contain an oxygen atom bonded to the carbenic center are known to exist as singlet ground states. The rational for this is that the lone pair electrons on the adjacent oxygen atom have a resonance stabilizing effect on the electron deficient carbenic center ... 

One of typical reactions of the Fisher-type metal carbene is interaction of the electron-deficient carbenic carbon with a pair of non-bonding electrons contributed by a Lewis base (B ) to generate a metal complex-associated ylide or a free ylide. The ylide intermediate thus generated is usually highly reactive and undergoes further reactions to give stable products (Figure 1). 

Transformations to the cyclotrimeric boiazines and cyclotetrameric tetraza-2,4,6,8,l,3,5,7-tetraboracanes also occur. The rate of dimerization for amino iminoboranes has been shown to be stabilized by bulky substituents (76,79,83). This stabilization through dimerization is essentially a [2 + 2] cycloaddition. There are a number of examples of these compounds forming cycloadducts with other unsaturated polar molecules (78). Iminoboranes can add to electron-deficient carbene complexes of titanium such as (C5H5)2Ti(CH2) [84601-70-7] by [2 + 2] cyclo addition, yielding the metallacycle shown in equation 26 (84). 

The reaction is catalyzed by cupric ions and presumably results from a copper-complexed carbene.8 The electron-deficient carbene with only six electrons in its outer valence shell is known to add across the O—H bonds of un-ionized carboxyl groups to form the methyl ester. 

The reaction is assumed to involve initial formation of a carbene, by decomposition of the diazo compound with loss of nitrogen, followed by reaction of the electron-deficient carbene with the lone pair of electrons of the arsenic atom. Thermolysis of diazo compounds in copper-catalyzed reactions is known to provide singlet carbenes or carbenoid species (17). 

This sulfoxide-magnesium exchange reaction could be successfully applied to a new synthesis of allenes (Scheme 3.12) [6]. The procedure is a novel method for synthesis of allenes from three components, ketones, chloromethyl p-tolyl sulfoxide, and sulfones, in relatively short steps. A key step is an attack of the lithium a-sulfonyl carbanion on the electron-deficient carbene carbon. /1-Elimination of the sulfoxyl group then occurs to give the allene. 

A similar duality is noted with alkylidene complexes derived from the same type of carbenes, but not containing any electron-donating heteroatoms capable of stabilizing the electron-deficient carbene carbon atom. These latter complexes have been synthesized in the hope that they are more reactive toward nonactivated olefins. 

Kreiter and Formacek have obtained C NMR data for several Cr and W carbene complexes (123) (Tables XXXVI and XXXVII). They found that increased shielding of the carbene carbon occurred when R = phenyl was substituted for R = methyl. They attributed this to n donation from the aromatic ring to the vacant p orbital on the carbene carbon. Also the carbene carbons in cis 7V-methyl carbenoid ligands appeared at higher fields than in the corresponding trans fV-methyl derivatives. Finally, the shifts of ail carbons of the R and R" ligands were downfield from their typical positions due to the electron withdrawing power of the electron deficient carbene. 

But we can use a curly arrow to move the negative charge towards the positively charged nitrogen, leaving a neutral species with a lone pair at carbon. A close look at the central carbon shows, however, that it has only two substituents—it is a carbene. Carbenes with adjacent lone pairs can often be thought of in this way, the lone pair partially delocalized onto the C atom to help stabilize the electron-deficient carbene. 

The reaction can be envisioned as proceeding via nucleophilic attack by the phosphorane carbon atom on the electron-deficient carbene carbon atom to form a betaine-like intermediate (XXVI) which subsequently fragments to form an enol-ether complex and free triphenylphosphine which then react to give the observed products (see Scheme 14). The observation of (CO)s-WP(CgH4CH3)3 in the product mixture when the reaction was carried out in the presence of P(CeH4CH3)3 supports this mechanism. 

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