Dynamic covalent chemistry relates to chemical reactions carried out reversibly under conditions of equilibrium control. The reversible nature of the reactions introduces the prospects of "error checking" and "proof-reading" into synthetic processes where dynamic covalent chemistry operates. Since the formation of products occurs under thermodynamic control, product distributions depend only on the relative stabilities of the final products. In kinetically controlled reactions, however, it is the free energy differences between the transition states leading to the products that determines their relative proportions. Supramolecular chemistry has had a huge impact on synthesis at two levels: one is noncovalent synthesis, or strict self-assembly, and the other is supramolecular assistance to molecular synthesis, also referred to as self-assembly followed by covalent modification. Noncovalent synthesis has given us access to finite supermolecules and infinite supramolecular arrays. Supramolecular assistance to covalent synthesis has been exploited in the construction of more-complex systems, such as interlocked molecular compounds (for example, catenanes and rotaxanes) as well as container molecules (molecular capsules). The appealing prospect of also synthesizing these types of compounds with complex molecular architectures using reversible covalent bond forming chemistry has led to the development of dynamic covalent chemistry. Historically, dynamic covalent chemistry has played a central role in the development of conformational analysis by opening up the possibility to be able to equilibrate configurational isomers, sometimes with base (for example, esters) and sometimes with acid (for example, acetals). These stereochemical "balancing acts" revealed another major advantage that dynamic covalent chemistry offers the chemist, which is not so easily accessible in the kinetically controlled regime: the ability to re-adjust the product distribution of a reaction, even once the initial products have been formed, by changing the reaction's environment (for example, concentration, temperature, presence or absence of a template). This highly transparent, yet tremendously subtle, characteristic of dynamic covalent chemistry has led to key discoveries in polymer chemistry. In this review, some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820020503%2941%3A9%3C1460%3A%3AAID-ANIE11111460%3E3.0.CO%3B2-N

Dynamic covalent chemistry.

Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3757%2820020503%29114%3A9%3C1528%3A%3AAID-ANGE11111528%3E3.0.CO%3B2-Z

Dynamische kovalente Chemie

Ring-closing metathesis (RCM) of dienes is one of the most important methodologies now in use for the assembly of cyclic organic compounds. First employed by Villemin and by Tsuji nearly three decades ago,1,2 the reaction has risen to astonishing prominence in organic synthesis over the past decade, owing largely to the development of easily handled catalysts that enable controlled reaction.3 RCM represents a key step in many synthetic sequences: recent reviews describe its use in, inter alia, construction of synthetically valuable building blocks such as heterocyclic rings containing phosphorus,4 sulfur,4 oxygen,5 or nitrogen,5,6 including aromatic heterocycles;7 spirocyclic,8,9 cyclophane,8 and polycyclic compounds;8,9 and compounds of biological and medicinal relevance such as peptidomimetics,10,11 carbohydrate derivatives,11-14 alkaloids,11,15-19 bioactive cyclic molecules,20,21 and polycyclic ethers,22 including macrocyclic aza-crown ethers23 and topologically interesting molecules and “molecular machines”.24,25 While the common rings of 5-7 members have historically been dominant, owing in part to their greater ease of access, important advances have been made in the synthesis of medium20,26-30 and macrocyclic16,17,23,27,31-35 targets. One aspect of this review will examine the increased tendency of many medium and large rings to participate in equilibrium metathesis, and the resulting implications for selectivity and yields.

Equilibrium ring-closing metathesis.

In the presence of the third generation Grubbs catalyst, the ring-expanding olefin metathesis of a monocyclooct-4-en-1-yl functionalized salen ligand and the corresponding Co(II)(salen) complex at low monomer concentrations results in the exclusive formation of macrocyclic oligomeric structures with the salen moieties being attached in an unsymmetrical, flexible, pendent manner. The TOF-MALDI mass spectrometry reveals that the resulting macrocyclic oligomers consist predominantly of dimeric to tetrameric species, with detectable traces of higher homologues up to a decamer. Upon activation under aerobic and acidic conditions, these Co(salen) macrocycles exhibit extremely high reactivities and selectivities in the hydrolytic kinetic resolution (HKR) of a variety of racemic terminal epoxides under neat conditions with very low catalyst loadings. The excellent catalytic properties can be explained in terms of the new catalyst's appealing structural features, namely, the flexible oligomer backbone, the unsymmetrical pendent immobilization motif of the catalytic sites, and the high local concentration of Co(salen) species resulting from the macrocyclic framework. This ring-expanding olefin metathesis is suggested to be a simple way to prepare tethered metal complexes that are endowed with key features--(i) a high local concentration of metal complexes and (ii) a flexible, single point of attachment to the support--that facilitate rapid and efficient catalysis when a bimetallic transition state is required.

Ring-expanding olefin metathesis: A route to highly active unsymmetrical macrocyclic oligomeric co-salen catalysts for the hydrolytic kinetic resolution of epoxides

Lothar Reif

Papers

Kinetics and thermodynamics of the metathesis reaction of cycloolefins. 2. Molecular weight distribution