Halocyclopropanes from Halocarbenes

Abstract

This chapter reviews methods for the generation of halocarbenes and the reaction of the latter with unsaturated substrates. Chemical transformations of the derived halocyclopropanes are discussed in sufficient detail to demonstrate the synthetic utility of this class. The formation of dihalocyclopropanes from dihalocarbenes was first accomplished in 1954 by Doering and Hoffmann who used chloroform t‐ butoxide to generate the dichlorocarbene. Since that time a variety of other methods have been developed for the generation of halocarbenes. The various methods are discussed.

Interfacial Processes—The Key Steps of Phase Transfer Catalyzed Reactions

“…This was confirmed experimentally because it was shown that under PTC conditions overall rate of the consumption of chloroform correlates with rate of the addition of DCC, therefore is a function of nucleophilicity of alkenes [26]. On the other hand, under classical conditions: treatment of chloroform with t-BuOK in strictly anhydrous solvent, DCC is generated irreversibly, because dissociation of trichloromethyl carbanion results in formation of insoluble KCl [24,25] (Scheme 13). The strongly promoted extraction mechanism, namely ion exchange between TAA chloride and sodium hydroxide producing TAA hydroxide that enter the organic phase where deprotonation of chloroform and further reactions take place, is excluded for two reasons: equilibrium of this ion exchange is unfavorable for TAA hydroxide, and particularly due to observation that attempts to use separately prepared TAA hydroxide for generation and reactions of DCC gave negative results-the carbene is mostly hydrolyzed.…”

“…Thus, inhibition of the alkylation by iodide anions is observed for carbanions generated via deprotonation of weak CH acids whereas the alkylation of carbanions derived from stronger CH acids (and also heteroacids) is not inhibited by iodide anions. Moreover since alkyl iodides are more active alkylating agents than chlorides, peculiar regularities can be observed-under similar conditions PTC alkylation of some strong CH acids proceeds more efficiently by alkyl iodide than alkyl chloride, whereas less acidic CH acids are alkylated by alkyl chlorides, but not by alkyl iodides [23,24] Moreover, no catalytic generation and reactions of dichlorocarbene was observed in the presence of these pyridinium salts. The experiments with these pyridinium salts clarify contribution of the variant of the interfacial mechanism known as modified interfacial mechanism (MIM) ( [17], pp.…”

“…Thus, inhibition of the alkylation by iodide anions is observed for carbanions generated via deprotonation of weak CH acids whereas the alkylation of carbanions derived from stronger CH acids (and also heteroacids) is not inhibited by iodide anions. Moreover since alkyl iodides are more active alkylating agents than chlorides, peculiar regularities can be observed-under similar conditions PTC alkylation of some strong CH acids proceeds more efficiently by alkyl iodide than alkyl chloride, whereas less acidic CH acids are alkylated by alkyl chlorides, but not by alkyl iodides [23,24] It appears therefore that inhibitory effect of iodide anions in PTC alkylation of carbanions is not due to competitive transfer of these anions into organic phase, but due to accumulation of iodide anions on the surface of the aqueous phase, hence its basicity is diminished. In this situation deprotonation of weak CH acids does not proceed, therefore alkylation of carbanions is inhibited, whereas more acidic carbanion precursors are deprotonated and the produced carbanions are efficiently alkylated by active alkylating agents-alkyl iodides.…”

“…Successful generation and reactions of dichlorocarbene (DCC) under action of aqueous NaOH on chloroform [8] was really surprising because all preceding reports stressed the necessity of strictly anhydrous conditions and even use of sublimed potassium t-butoxide as a base [24]. Efficiency of the PTC system is due to a few reasons: a) 50% (saturated) aqueous NaOH, in which approximately there is one molecule of water for one ion, is in fact a strong desiccation agent, hence there are no traces of water in the organic phase; b) upon deprotonation of chloroform on the interface generated trichloromethyl anions are introduced into organic phase as lipophilic ion pairs with TAA cation.…”

“…This undesired lack of selectivity is due to reversibility of the dissociation of initially generated dibromochloromethyl anions to bromochlorocarbene and its reactions with halogen anions [26]. On the other hand, irreversible dissociation of dibromochloromethyl anions generated in the presence of potassium t-butoxide assures selective formation of bromochlorocyclopropanes [24].…”