Cyclization reactions cation

The C-coordinated thiazolium complexes are the result of the proton-induced cyclization reactions (980M513). Thus, complex 1 on protonation with tetrafiuoroboric acid yields the C-coordinated thiazolium structure 2. In turn, the nitrile complex 3 under these conditions is transformed to the thiazolium cationic species 4. Protonation of the amido complex 5 with tetrafiuoroboric acid also results in a cyclization but it proceeds differently. The amino group of the CONH2 moiety is lost and BF3-framework is coordinated via the carbonyl oxygen in an overall neutral complex 6. 

Closely related to the polyepoxide cascade procedure for the synthesis of polycyclic systems is Corey s biomimetic-type, nonenzymatic, oxirane-initiated (Lewis acid-promoted) cation-olefin polyannulation. By this strategy, compound 96, containing the tetracyclic core of scalarenedial, was constructed by exposure of the acyclic epoxy triene precursor 95 to MeAlCl2-promoted cyclization reaction conditions (Scheme 8.25) [45]. 

In the oxygen-independent Type III reactions the excited/sensi-tized psoralen donates its excitation energy directly to, or reacts with, the target compound. This occurs if the substrate and the target compound (e.g., DNA) are already in close proximity or intercalated. The reactions will proceed very rapidly via the excited singlet state, and are, typically, cyclization reactions or electron-transfer between the sensitizer and the target. In addition, the psoralen can be ionized, either directly or via the excited state, and react with the target compound in the form of a radical cation. Furocoumarins are also employed in treatment of cutaneous T-cell lymphoma and some infections connected with AIDS, by so-called photopheresis processes [71, 74-76]. In this case, peripheral blood is exposed to, e.g., photoactivated (sensitized) 8-methoxypsoralen (8-MOP) in an extracorporeal flow system. This... 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Since Pedersen s original work on the use of cations to template the formation of crown ethers [18-20], a large number of different templating agents for macro-cyclization reactions have been reported. While the initial work concentrated on the use of metal cations, further developments demonstrated that species with hydrogen bonding donor or acceptor properties could be equally useful to template the synthesis of macrocyclic molecules. 

Alternative, also stereoselective, routes to allenic steroids take advantage of cationic cyclization reactions [108] or [2,3]-sigmatropic rearrangements [109]. For example, the allenic Michael acceptor 112 was prepared with 57% chemical yield by reaction of mestranol (111) with diethyl chlorophosphite and was found to inhibit the sterol biosynthesis of the pathogen responsible for Pneumocystis carinii pneumonia (PCP), the most abundant AIDS-related disease (Scheme 18.36) [110]. 

The benzannulated enyne-allenes 48 were likewise synthesized in situ from coupling between 41b and the bromoallene 47 (Scheme 20.11) [39]. Under the reaction conditions, 48 presumably underwent a spontaneous cation-mediated Myers-Saito cyclization reaction with a concomitant 1,2-shift of the trimethylsilyl group to give the naphthalene derivatives 49. 

Scheme 20.11 Cation-mediated Myers-Saito cyclization reaction.

Further examples of catalytic antibodies that are presumed to control rotational entropy are AZ-28, which catalyses an oxy-Cope [3.3]-sigmatropic rearrangement (Appendix entry 13.1) (Braisted and Schultz, 1994 Ulrich et al, 1996) and 2E4, which catalyses a peptide bond isomerization (Appendix entry 13.3) (Gibbs et al., 1992b Liotta et al., 1995). Perhaps the area for the greatest opportunity for abzymes to achieve control of rotational entropy is in the area of cationic cyclization reactions (Li et al., 1997). The achievements of the Lerner group in this area (Appendix entries 15.1-15.4) will be discussed later in this article (Section 6). 

The cyclic metabolite 11.169 was also a substrate in further biotransformations, being (V-demethylated to the corresponding endocyclic imine, and oxidized to phenolic metabolites. Very little if any of the secondary amine metabolite (11.168) appeared to undergo direct (V-demethylation to the primary amine, in contrast to many other tertiary amines, presumably due to very rapid cyclization of the secondary amine facilitated by steric and electronic factors. The possibility for the iminium cation (11.169 H+) to become deprotonated (a reaction impossible for the iminium 11.166 in Fig. 11.20) should also drive the cyclization reaction. 

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. 

Cyclization Reactions Involving Radical Cations and Radical Anions... 

Whereas the design and application of free radical cyclization reactions have been extensively covered in excellent reviews [3-5], there is no comprehensive report on the synthetic application of their charged counterparts radical cations and radical anions. 

On the one hand, this particular feature makes it more difficult to distinguish between reactions involving radical cations, free radicals or carbenium ions, but on the other hand the chemist acquires an additional tool to control the course of the intended reaction. Some illustrative examples of cyclization reactions that utilize cleavage of the radical cations, primarily generated by single-electron oxidation, will be given in the following sections. 

For clarity and convenience the following examples of radical-ion cyclization reactions are compiled according to the type of the electron donor from which the radical cation is generated. 

Again, the exclusive formation of six-membered rings indicates that the cyclization takes place by the electrophilic attack of a cationic center, generated from the enol ester moiety to the olefinic double bond. The eventually conceivable oxidation of the terminal double bond seems to be negligible under the reaction conditions since the halve-wave oxidation potentials E1/2 of enol acetates are + 1.44 to - - 2.09 V vs. SCE in acetonitrile while those of 1-alkenes are + 2.70 to -1- 2.90 V vs. Ag/0.01 N AgC104 in acetonitrile and the cyclization reactions are carried out at anodic potentials of mainly 1.8 to 2.0 V vs. SCE. 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

The one-electron chemistry of enols has been intensively studied by Schmit-tel [108]. He has shown that the thermodynamic stability order of the ketone tautomer and the enol tautomer in the solution phase is inverted upon one-electron oxidation [109, 110]. Therefore enols are much more easily oxidized than the corresponding ketone tautomer. Supposing that the enolization is faster than the electron transfer, it ought to be possible to oxidize the enol present in small amounts beside the ketone in the equilibrium mixture. The following cyclization reactions are as useful approach to the chemistry of enol radical cations and can be considered as the a-umpolung of ketones. 

---