Cyclization reactions termination

CATIONIC CYCLIZATION REACTIONS TERMINATED BY PBVACOL REARRANGEMENTS... 

The cyclization reactions discussed here either involve the intramolecular reaction of a donor group D with an acceptor group A or a cyclizing dimerization of two molecules with two terminal acceptors and two donors. A polymerization reaction will always compete with cyclization. For macrolides see p. 146 and p. 319 — 329. 

An approach to isobacteriochlorins1 ln-e makes use of Pd(II) or metal-free bilatrienes 1 as starting materials. Cyclization of the corresponding bilatriene derivatives is induced by base in the presence of palladium(II) or zinc(II) which exercise a template effect. Zinc can be readily removed from the cyclized macrotetracycles by acid whereas palladium forms very stable complexes which cannot be demetalated. Prior to the cyclization reaction, an enamine is formed by elimination of hydrogen cyanide from the 1-position. The nucleophilic enamine then attacks the electrophilic 19-position with loss of the leaving group present at the terminal pyrrole ring. 

Polyene cyclizations are of substantial value in the synthesis of polycyclic terpene natural products. These syntheses resemble the processes by which the polycyclic compounds are assembled in nature. The most dramatic example of biosynthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, an enzyme not only to induces the cationic cyclization but also holds the substrate in a conformation corresponding to stereochemistry of the polycyclic product.17 In this case, the cyclization is terminated by a series of rearrangements. 

Tandem addition-cyclization reactions can be used for a simultaneous construction of the central and terminal rings. This is illustrated in Equation (10) by the synthesis of 121 from 120 <2002BMC1275>. 

Another method of activation we considered was the use of a secondary amine to generate a more electrophilic iminium species, examples of which have been used in vinylsilane-terminated cyclization reactions, particularly by Overman and co-workers [Eq. (4.8)] [51]. In our case, the unsaturated iminium ion would be activated for... 

The benzoquinone 66 is similarly prepared by the regioselective cycloaddition of 64, derived from 63. The cyclization reaction is based on the electronic effect of the substituent of 65 [34]. The maleoylcobalt complex 67, substituted by PPh3, is unreactive towards terminal alkynes. The reaction course is altered... 

Hypothetical (carbene)gold(i) structures of intermediates and reaction coordinates have been calculated (B3LYP/ 6-31G and LAN2DZ levels) for (H3P)Au+-catalyzed cyclization reactions of terminal enynes. The endocyclic skeletal rearrangement reactions were found to proceed exclusively via cyclopropylcarbene complexes.240... 

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

The very first example of the catalytic reductive cyclization of an acetylenic aldehyde involves the use of a late transition metal catalyst. Exposure of alkynal 78a to a catalytic amount of Rh2Co2(CO)12 in the presence of Et3SiH induces highly stereoselective hydrosilylation-cyclization to provide the allylic alcohol 78b.1 8 This rhodium-based catalytic system is applicable to the cyclization of terminal alkynes to form five-membered rings, thus complementing the scope of the titanocene-catalyzed reaction (Scheme 54). 

Alkynes are interesting radical acceptors for cyclization reactions because the products contain double bonds that can be subjected to further transformations. In the case of terminal alkynes, the desired products can be obtained in high yields as single isomers. With non-terminal alkynes as acceptors, the alkene products are generated as mixtures of ( )- and (Z)-isomers in high yields but with low selectivity [36],... 

Grigg expanded his Pd-catalyzed cascade cyclization reactions to include carbonylation as the termination step [427]. Thus, indoline 329 is obtained in excellent yield and the spiroindoline 330 is secured as a single diastereomer. Thallium acetate results in significant improvement in these reactions by allowing for low-pressure carbonylation. 

The rhodium-catalyzed hydroboration has opened the way to cyclization reactions starting from dienes [92], For instance, rhodium-catalyzed hydroboration of the terminal alkenyl group of an os/Tunsaturated lactone followed by reaction with the PTOC-OMe chain transfer reagent afforded the bicyclic a-S-pyridyl lactone in 63% yield (Scheme 39). After oxidation of the sulfide with m-CPBA, thermal elimination of the sulfoxide afforded the corresponding a-methylene lactone in 65% yield. Interestingly, such bicyclic a-methylenelactones are substructures that can be found in many natural products such as mirabolide [93]. 

The palladium-catalyzed elimination-cyclization reaction of biscarbamates 254 opens up a further route to nitrogen-substituted allenes (Scheme 8.68) [149]. This transformation proceeds for certain substitution patterns with surprisingly high regioselectivity, favoring allenes 256 with a terminally unsubstituted C=C bond. 

The symmetrical anhydride is prepared using dicyclohexylcarbodiimide in dichloromethane, the urea and solvent are removed, and the anhydride is dissolved in dimethylformamide and added to the peptide-resin (see Section 2.5). The anhydride is a more selective acylating agent than the 0-acylisourea and, thus, gives cleaner reactions than do carbodiimides, but twice as much amino-acid derivative is required, so the method is wasteful. It avoids the acid-catalyzed cyclization of terminal glutaminyl to the pyroglutamate (see Section 6.16) and is particularly effective for acylating secondary amines (see Section 8.15). 

The rate constants for reaction of Bu3SnH with the primary a-alkoxy radical 24 and the secondary ce-alkoxy radical 29 are in reasonably good agreement. However, one would not expect the primary radical to react less rapidly than the secondary radical. The kinetic ESR method used to calibrate 24 involved a competition method wherein the cyclization reactions competed with diffusion-controlled radical termination reactions, and diffusional rate constants were determined to obtain the absolute rate constants for the clock reactions.88 The LFP calibrations of radical clocks... 

Although terminal alkynes can easily be converted into vinylidene complexes, vinylidene complexes have not yet been extensively used as intermediates in organic synthesis [150,546,576-578,944]. Some cyclization reactions, which might proceed by transient formation of vinylidenes, are listed in Table 3.23 (see also Sections 2.1.5.1 and 2.2.2). 

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. 

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