Carbocations cyclization reactions

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

Recentiy published crystal structures of antibody 4C6, an antibody that catalyzes another cationic cyclization reaction (Figure 6), revealed that this antibody has exquisite shape complementarity to its eliciting hapten 5. The active site contains multiple aromatic residues which shield the high-energy intermediate from solvent and stabilize the carbocation intermediates through cation-7r interactions. 

Because the immediate product of the polyene cyclization is a carbocation, the reaction often yields a mixture of closely related compounds resulting from the competing modes of reaction of the carbocation. The products result from capture of the carbocation by solvent or other nucleophile or by deprotonation to form an alkene. Polyene cyclization can be carried out on reactants which have special structural features that facilitate transformation of the carbocation to a stable product. Allylic silanes, for example, are... 

Stereoisomeric alcohols (93) and (94) yielded identical ring-expansion products [e.g. (97)] on formation of carbocations.168 This is evidence of a stepwise reaction in sterol biosynthesis, whereby a tertiary cation [e.g. the model (95)] rearranges to a secondary cation (96)-an anti-Markovnikov rearrangement . The synthetic aspects of biomimetic cyclizations of isoprenoid polyenes were reviewed.169 Included was a detailed discussion of carbenium ion-initiated cyclizations, with a discussion of the different mechanisms that have been proposed. A novel biomimetic carbocation polyene cyclization of a daurichromenic ester was reported an unusual 2 + 2-carbocation cyclization occurred as a side reaction.170... 

S. R. Angle, H. L. Mattson-Amaiz, The Formation of Carbon-Carbon Bonds via Benzylic-Cation-Initiated Cyclization Reactions, in Advances in Carbocation Chemistry (J. M. Coxon, Ed.) 1995, 2, JAI, Greenwich, CT. 

Clearly the course of these cyclization reactions is dependent upon the silicon group. In this regard, cyclization of (82) affords the steroid nucleus (83 Scheme 40). The formation of (83) was attributed, in part, to a transition state preference for the formation of the linear vinyl carbocation (84b) rather than the bent vinyl cation (84a), which would be produced in an endocyclic cyclization. The formation of (81) was controlled by the generation of the -silyl carbocation (85a), which may be a precursor to an a-silyl ketone, which undergoes protodesilylation. It is not known whether the formation of (81) as the major cyclization product occurs through a kinetic pathway or by Wagner-Meerwein rearrangement of the kinetically prefened linear carbocation (85b). 

In general, carbonyl groups do not function as good initiators in vinylsilane-mediated cyclization reactions and relatively few examples exist. The cyclization of vinylsilanes with ketones or aldehydes as initiators is a highly underdeveloped reaction that holds considerable potential. As reported by Tius and coworkers, treatment of aldehyde (13) with a catalytic amount of p-toluenesulfonic acid gave a mixture of the tetralins (14) and (15) in a combined yield of 53%, with lesser amounts of the enone (16 Scheme 8). The enone system presumably arises from the intramolecular 1,3-hydride transfer of the intermediate a-silyl carbocation (17). Similarly, the vinylsilane (18) undergoes cyclization to produce the disub-stituted benzene derivative (19), although yields are low. 

The subsequent cyclization reaction, which probably takes place through a carbocation created by attack of a proton on the oxygen atom of fhe epoxide ring (Fig. 

Reaction of a divinyl alkyne such as 137 with aqueous acid generates a conjugated ketone (138), via hydration of an intermediate vinyl cation. Subsequent treatment with a mixture of phosphoric and formic acids leads to a new, oxygen-stabilized carbocation (139), which reacts with the adjacent alkene (a cyclization reaction) to form 140. Elimination led to the conjugated ketone (141). 3 This cationic ring-closing reaction... 

The most commonly used resin in his-azide resists is poly(c/5-isoprene), which is cyclized hy treatment with a mineral acid (Scheme 6.7). The cyclization reaction is quite similar to cationic polymerization. In the first reaction step, the acid cation adds to a double bond, producing a carbocation. The reaction of a nearby double bond with this ion leads to cyclization. ... 

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