Carbenes from haloforms

In the 1950s and 1960s chemists learned how to generate carbenes from haloform, diazirine and diazo compound precursors as transient intermediates in solution. [1,5,6] The chemists of this era identified the products of carbene reactions and learned how to make these reactions synthetically useful. They postulated a framework for carbenes (Scheme 1) with ground or low lying triplet states which is still the starting point in all mechanistic discussions. 

The production of carbenes from haloforms (Eq. 10.54) is an interesting reaction. The reaction sequence displays second-order kinetics, first order in both base and haloform. This supports a mechanism involving an equilibrium deprotonation prior to rate-determining a-halogen departure. The loss of an equivalent of HCl from HCCI3 constitutes an elimination reaction, and is specifically called a 1,1-elimination or an a-elimination. 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

When carbenes are generated from haloforms with potassium hydroxide, exclusive insertion of carbene into a /3-C-H bond has been reported <1980JOM(198)29> (Scheme 57). 

The formation of dihalocarbene is one of the most useful phase-transfer processes developed in organic chemistry. The dihalocarbenes, once generated from haloform and base, can undergo addition or insertion reactions (3, 11, 12). If the double bond is complexed to a metal, addition by the carbene will not occur, but rather insertion into a saturated carbon-hydrogen bond will take place. 

Dihalocarbenes generated from haloforms and strong bases e.g. alkoxides) or from haloforms and alkali metal hydroxides under phase transfer conditions " or organomeicuiytrihalomethanes, add to azomethines to yield 2,2-dihaloaziridines (49 equation 30). The following carbenes have been used for such purposes dichlorocarbene, " dibromocarbene, " difluorocarbene, bromochlorocar-bene and bromofluorocarbene. The addition of dihalocarbenes to azoxybenzene or azobenzene affords dihaloaziridines e.g. 50 equation 31) among other products. 

It should be stressed that this methodology is of general use for generation of other dihalocarbenes via oc-elimination of hydrogen halide from haloforms, and many other carbenes which can be generated via base-induced a-eliminations ... 

Among the oldest and more spectacular applications of PTC is the generation of carbenes (mostly dihalocarbenes) from haloforms, aqueous concentrated alkaline hydrox-... 

The generation of carbenes under sonication from haloforms and strong bases in the solid state appeared in the literature in 1982 (Eq. 38). 05 method can be performed in common cleaning baths and is thus accessible to many laboratories. Addition to olefins occurs in yields at least equivalent to or higher than conventional methods, with the advantage of shorter times (p. 344). 

Intermediate carbenes are also involved in the alkylation by haloforms of carbanions derived from Schiff bases of a-ammo esters [126] or aminomalonates... 

Addition of bromochlorocarbene (carbenoid) to an alkene results in the formation of 1-bromo-1-chlorocyclopropanes. The preparative value of this process depends on the structure of the carbene source, the type of base used for a-elimination of hydrogen bromide from the haloform, reaction conditions etc. 

Elimination Reactions. t-BuOK is a widely used base for both a- and /3-elimination reactions. It is the most effective base in the conventional alkoxide-haloform reaction for the generation of dihalocarbenes. This procedure still finds general use (eq 19), but since it requires anhydrous conditions, it has been replaced to a degree by use of phase-transfer catalysts. Vinylidene carbenes have also been produced from the reaction of a-halo allenes with f-BuOK. ... 

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