Carbenes synthetic equivalents

The synthon will be, in a lower valeney state - if X is C then it will be a carbene or the synthetic equivalent of a carbene. Let s see how this disconnection works out for epoxides. Taking X = O first we have... 

The diazo compound combined with the Rh(II) salt tells you that a carbenoid is involved. The carbenoid can be drawn in the Rh=C form or as its synthetic equivalent, a singlet carbene. In either case, C3 can... 

Cyclohexadiene 45 was converted to 46 by what has proven to be a general method for preparation of the cyclohexa-2,4-dien-l-one ring system.2 Fragmentation of the aziridinyl imine in 46 at 110 °C gave an intermediate diazoalkane which underwent an intramolecular 1,3-dipolar cycloaddition to give the pyrazoline 47. At 140 °C, pyrazoline 47 expelled N2 and rearranged to the tricyclic ketone 48. The development of this and related bicyclizations29 illustrated a practical synthetic equivalence of an intramolecular diene-carbene 4-1-1 cycloaddition in the cyclohexa-2,4-dien-l-one series. 

We now turn to reagents which are important in context with the element/halogen exchange Compounds of the type 8 would be interesting reagents for nucleophilic halomethylation but are quite unstable due to carbene formation. Compound 9 would be an attractive synthetic equivalent for the synthons 8. As will be shown... 

Further fluorinated synthons 20 (equation 17)92 and 21 lead to Reformatsky intermediates which are synthetic equivalents of a formal 4,4-difluoroacetoacetate dianion and of a carbalkoxy trifluoromethyl carbene, respectively. The latter has been exploited in a synthesis of E-22 and Z-22, both inhibitors of GABA aminotransferase (equation 18)93. 

Many of these reactions also involve carbene intermediates [32] but they are treated separately because their synthetic equivalence is different. The chemistry described in this section allows the disconnection of targets to carbon nucleophiles and one-carbon fluorinated electrophiles. 

Casey and coworicers have shown that ketone etiolates add efficiently to a,3-unsaturated vinyl carbene complexes (164), irrespective of 3,3-disubstitution on the complex or high substitution on the enol-ate 133 thus, contiguous 3 and y quaternary centers are easily assembled. When coupled with the ease of release of the carbene ligand from the complexes by either oxidation to the ester functionality1331 or elimination to the corresponding enol ether,133 the vinyl carbene complexes are synthetic equivalents for a,3-unsaturated esters or a,3-unsaturated aldehydes, respectively (Scheme 63). 

Reactions of this type represent an important group of methods employed in cyclopropane synthesis. The course of these cycloadditions is described in the formal equation shown in Scheme 2.132. Independent of the method of generation or its actual nature, the Ci addend can be viewed as a synthetic equivalent to the carbene 395, at least in terms of its ability to form two new C-C bonds at a single carbon center. 

Starting from (silyl)(phosphino)diazomethane derivatives, stable pseudo-diazoalkenes and carbenes have been obtained. The diazomethylenephosphoranes are very reactive dipolarophiles but are also synthetic equivalents of naked carbon C . The stable carbenes react in a similar manner to their transient analogues, but also exhibit new reactions the synthesis of unsaturated three-membered heterocycles is particularly noteworthy. Ring expansion reactions involving the latter are of special interest since they afford novel non-antiaromatic four-7t-electron four-membered heterocycles. 

In this section, transfer to C-C double bonds of the divalent C, building blocks of type A, either as free carbenes or via synthetic equivalents thereof, are covered. 

This section deals with the transfer of the following carbenes (or their synthetic equivalents) to alkenes. 

When the donor character of the amino substituent at the transition-metal-carbene carbon atom is reduced, it should be possible to influence the thermal stability and reactivity in favor of the desired cyclopropanation process. Indeed, pyrrol-1 -ylcarbene complexes 18 of chromium, molybdenum and tungsten do exhibit the desired reactivity. In the last step, the pyrrole ring of 19 can be converted to the NH2 function in 20 after oxidative cleavage with ozone.In this respect, the pyrrole heterocycle represents a synthetic equivalent of the amino function. 

The direct synthesis of benzocyclopropene (1) from benzyne and a carbene or from synthetic equivalents thereof has not yet been realized, but arc-generated carbon reacted with benzene at — 196°C to give benzocyclopropene (1) in 11% yield, together with toluene (24%), cyclo-heptatriene (17%), 7-phenylcycloheptatriene (21%) and heptafulvene (17%). Phenylcarbene in an excited state is a possible intermediate in the formation of benzocyclopropene. ... 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

Besides reacting with nucleophiles, penicillin-derived sulfenic acids are trapped by the electron-poor carbon atom of alkynes, allenes and carbenes [47]. The conjugate addition to alkynes, first explored by Barton et al. [94], generates ene-sulfoxides 152, which can be considered synthetic equivalents of thioesters... 

Singlet carbenes are formed by treatment of CHCI3 with t-BuOK (results in loss of HCl to give iCCy, by loss of N2 from diazo compounds, such as diazomethane (CH2N2), or by reaction of CH2I2 with zinc-copper amalgam (cyclo-propanation with the resulting CH2 synthetic equivalent, called a carbenoid, is the Simmons-Smith reaction). 

Chromium (and tungsten) imino carbene complexes 113 are found to be synthetic equivalents for nitrile ylides on the basis of the resonance structure (Scheme 5.23) [34]. The reaction of the imino carbene complex 113 with alkyne 114 affords pyrrole 115. Imidazoles 116 and 120, pyrrolidines 118, and oxazoline 119 are also obtained by the [3+2] cycloaddition of the imino carbene complexes 113 with benzonitrile, alkenes 117, and benzaldehyde, respectively. Although the regiochemical outcome of these reactions is unpredictable, the regioselectivity can be correlated with the resonance structure in the case of the reaction with 3-hexyn-2-one. 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

Diazoester aziridinations may be carried out in ionic liquids [39]. Other carbene equivalents have been investigated in aziridination reactions, though not to the same extent as diazocarbonyl compounds. Dibromo(tert-butyldimethylsilyl)me-thyllithium, for example, aziridinates N-arylimines to give l-bromo-2-aryl-3-silyla-ziridines these compounds function as useful synthetic intermediates, reacting... 

The potential synthetic utility of titanium-based olefin metathesis and related reactions is evident from the extensive documentation outlined above. Titanium carbene complexes react with organic molecules possessing a carbon—carbon or carbon—oxygen double bond to produce, as metathesis products, a variety of acyclic and cyclic unsaturated compounds. Furthermore, the four-membered titanacydes formed by the reactions of the carbene complexes with alkynes or nitriles serve as useful reagents for the preparation of functionalized compounds. Since various types of titanium carbene complexes and their equivalents are now readily available, these reactions constitute convenient tools available to synthetic chemists. 

Almost all stable carbenes behave as 2-electron-CT-donating ligands with a few exceptions. In particular, in almost all cases corresponding Rh(I) complexes were targeted due to the easy synthetic method. An exception is the cyclopropenylidene carbene, with an extremely acute carbene angle. In this case, a second equivalent of carbene squeezes into the rhodium center, eliminating a chloride anion, giving the cationic dicarbenic rhodium(l) complex [51] (Scheme 5). 

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