Reaction macrocyclization

The Ciamician-Dennstedt reaction has been used to prepare macrocycles. Reaction of 2,3-alkyl linked indole derivatives 10, 11, 13, and 15 with phenyl(trichloromethyl)-... 

Scheme 1 outlines the retrosynthetic analysis of the Woodward-Eschenmoser A-B variant of the vitamin B12 (1) synthesis. The analysis begins with cobyric acid (4) because it was demonstrated in 1960 that this compound can be smoothly converted to vitamin B12.5 In two exploratory corrin model syntheses to both approaches to the synthesis of cobyric acid,6 the ability of secocorrinoid structures (e. g. 5) to bind metal atoms was found to be central to the success of the macrocyclization reaction to give intact corrinoid structures. In the Woodward-Eschenmoser synthesis of cobyric acid, the cobalt atom situated in the center of intermediate 5 organizes the structure of the secocorrin, and promotes the cyclization... 

Finally, allyl radicals have successfully been employed in macrocyclization reactions, in which the slower rate of reaction of allyl radicals with hydrogen donors turned out to be advantageous46. Thus, radical 11 cyclizes in 1 A-endo mode to provide, after trapping with tin hydrogen, the product 12 as a fi -mixture of the C2/C3 double bond. No products derived from 6-exo or 10-exo cyclizations could be found (equation 8). This can be rationalized by assuming a faster rate of addition of the nucleophilic allyl radical to the electron-deficient terminal double bond than to the C6 or CIO double bonds. 

RCM-based macrocyclization reactions as they potentially sequester the catalyst in an unproductive form. A recent total synthesis of gloeosporone 86 addresses this aspect and describes a simple, yet efficient way to overcome this limitation [31]. 

One of the most convenient of these tether-directed functionalization strategies exploits the macrocyclization of C60 with bismalonate derivatives in a double Bingel reaction.156,571 With the exception of the cis-1 bisaddition product, all possible bisaddition patterns have been obtained by this macrocyclization reaction (Figure 13). As a general... 

In a recent study, some mechanistic aspects of this templated process have been determined quantitatively [28]. Using UV-Vis spectroscopy to monitor the kinetics of the macrocyclization reaction, it has been established that the rate of ring closure of the cationic precursor to the [ljimidazoliophane (4) is increased up to ten times in the presence of 0.04 mol/1 solution of a chloride source. The chloride stabilizes the transition state (i.e. a kinetic template) favouring the macrocyclization through hydrogen bonding. 

The field of alkyl radical macrocyclization reactions was further augmented with an n + 1) strategy, which incorporates a CO unit in the macrocycle [93], Thus, in the presence of highly diluted (0.005-0.01 M) (TMS)3SiH, co-iodoacrylates underwent an efficient three-step radical chain reaction to generate 10- to 17-membered macrocycles in 28-78% yields, respectively (Reaction 7.82). 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

Diisonitriles 98 and 101 were subsequently employed in a double Ugi macrocyclization reaction under pseudo-dilution conditions, where the di-... 

Diacid 108, diamine 109, and diisonitrile 110 were all successfully used in double or fourfold Ugi macrocyclization reactions [78, 97]. 

In the previous cases, the two or four Ugi reactions taking place were either identical or similar, but in this case, the reaction taking place at the oxime side involves other components than the reaction on the carboxylic acid side. In effect, two four-component reactions are combined to give a five-component macrocyclization reaction. 

One of the most striking demonstrations of the Heck reaction on solid phase was an efficient macrocyclization reaction by Hauske et al. They cyclized the resin-bound species 19 under mild conditions and obtained products with high post-cleavage purity (Scheme 19).49 The efficiency of these reactions for a variety of structural modifications in the ring seems to suggest that the pseudodifution effects of site isoiation on resin are important. 

Complexes of nickel(II), copper(II), cobalt(III), zinc(II), iron(II), palladium(II), platj-num(II) and vanadyl can be obtained. Although the reaction sequence is fairly general for metal ions, it is not easily extendable to substituted 2-aminobenzaldehydes. However, 2-amino-5-me-thylbenzaldehyde has recently been used successfully in the macrocyclization reaction.147... 

Include them Synthetic chemists are accustomed to publishing communications or letters in which the conditions of relatively standard procedures are summarized in a scheme. Except for special reactions such as macrocyclizations, reaction concentrations are rarely included in these schemes. However, the... 

Hayward CM, Yohannes D et al (2002) Total synthesis of rapamycin via a novel titanium-mediated aldol macrocyclization reaction. J Am Chem Soc 115 9345-9346... 

Figure 6 Representative examples of C6o bis-adducts directly produced by the Bingel macrocyclization reaction.

The synthesis of interlocked molecules has become commonplace over the past 25 years with the gradual development of a number of highly facile template methods for their construction. What were once laboratory curiosities have now taken a prominent place in the broad field of supramolecular chemistry, especially regarding their uses and further potential as molecular switches and machines [1], We present here an overview of the main synthetic approaches to these molecules, with a focus on methods in which macrocyclization reactions result in interlocked products. The analysis is by no means meant to be comprehensive or exhaustive in detail, but rather to convey the variety and utility of the selected synthetic strategies in generating abiotic rotaxane and catenane superstructures. 

Figure 10.1 Clipping strategies in macrocyclization reactions resulting in interlocked products such as [2]rotaxanes and [2]catenanes.

The macrocyclization reaction described above has been used to generate a great number of catenane (12) and rotaxane (13) architectures (Scheme 10.4) using both crown ethers [preformed macrocyclic components 14 (strategy A)] and hydroqui-none-based dumbbell-shaped polyethers [preformed acyclic components 15 ( clipping )] as templates [14b, 15]. These templates are also relatively robust with regard to the substitution of different groups into both the tetracationic cyclophane and the neutral frameworks. 

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