Covalent self-assembly

One-Pot Reactions. Covalent Self-Assembly Based on Preorganization... 

Figure 2.8. Some examples of covalent self-assembly. Note "zipper reaction (bottom).

Figure 2.9. Further examples of covalent self-assembly of a tetracyclic hydrocarbon (top) the Ugi reaction (middle) atropine synthesis (bottom).

A limiting case of covalent self-assembly may be considered to be the formation of the curved carbon structures of the spheroidal fullerenes C(,q, C70, etc. [9.9a] and of carbon nanotubes [9.9b] in the high-temperature regime of carbon vapour that permits a certain structural fluidity. 

There are many kinds of capsules but few have the capacity to position co-guests in predictable orientations. We used the ability of 1.24.1 to do so, and applied it to evaluate hydrogen-bonding interactions between boronic acids, carboxylic acids, and primary amides [52], The phenyl boronic acids are useful as components of covalently self-assembled systems [53], and we found that the p-methyl, methoxy, ethyl, and isopropyl derivatives all fit as symmetrical dimers inside I.24.I. The structure of the boronic acid dimer has been debated but a recent theoretical study found the doubly hydrogen-bonded exo/endo conformer (Fig. 10) to be lowest in... 

Both of the above examples correspond to assembly processes that involve non-covalent followed by covalent bond formation of course, other sequences are also possible as is totally covalent self-assembly - strategies discussed by Lindsey as early as 1991."... 

Slone R.V., K.D. Benkstein, S. Belanger, J.T. Hupp, LA. Guzei, and A.L. Rheingold (1998). Luminescent transition-metal-containing cyclophanes ( molecular squares ) Covalent self-assembly, host-guest studies and prehminary nanoporous materials applications. Coord. Chem. Rev. 171, 221-243. 

The dimeric borazaromatic compound 32 was covalently self-assembled via a dehydration reaction of monomeric bis(borazaaromatic) ether 31 using 4 A molecular sieves in acetone, as determined by NMR, X-ray, and MALDI-TOF mass spectrometry (Scheme 14) (1999CC2279). The latter method was used to monitor the dehydration reaction over 12 days. Acyclic oligomers 33 were found to predominate as the initial kinetic products... 

In comparison to abundant examples of noncovalent supramolecular assemblies,relatively few structures have been built with strong covalent bonds. This is due to the fact that normal covalent bonds are not easily broken and reformed. One can manipulate the temperature and conditions so that the formation of stable imines, esters, disulfides, hydrazones, and boronate esters is reversible. Some examples of these covalent self-assembled systems include disulfide hosts and covalent organic frameworks. ... 

Figure 8 Formation of Gd +-loaded nanoparticles through non-covalent self-assembly of guest inclusion complexes between alkylated dextran, poly-/S-cyclodextrin, and adamantyl-modified Gd-D03A derivatives. The alkyl chains on the dextran are in yellow, and the Gd-D03A derivatives are represented by the pnrple cylinders. (Adapted from Ref. 32. Wiley-VCH, 2008.)...

Covalent self-assembly A self-assembly process that involves reversible covalent bonding. Synonym of dynamic covalent chemistry. 

Dynamic covalent chemistry Self-assembly processes that involve reversible covalent bonding such as imine formation. Synonymous with covalent self-assembly. 

If we do not like this, a way out is to require self-assembled species to hold together by weak bonds only, and to use a term such as self-construction for the cases of "covalent self-assembly", as proposed in the introduction (section 1.1.2). This would cause the defmition of self-assembly to narrow down to what most chemists, when first asked, would call self-assembly. 

Prof. Eschenmoser defended his position by pointing out that these reactions are in fact quite distinct from the normal synthetic processes, in which each step requires a very specific instruction. He felt that perluq>s it will be best to keep the terms covalent and non-covalent self-assembly. I agree that it is useful to distinguish the two cases, but it seems to me more efficient to use the terms self-assembly and self-construction. 

The unexpected example of the covalent self-assembly of flexible 16-membered macrocyclic tetraphosphines 102 and 103 was found in the course of condensations of secondary diphosphines with formaldehyde and aralkylamines, including those with various heteroaryl fragments (Scheme 12.39). 

Scheme 12.39 Covalent self-assembly of 16-membeied PJSI-containing macrocycles 102 and 103...

The found covalent self-assembly process allowed also to obtain a series of optically active tetraphosphine ligands 103 as single R5S/ -stereoisomers on the basis of various chiral amines [98]. 

The covalent self-assembly approach in the course of a Mannich-type condensation was used for the synthesis of P,N-containing cyclophanes with an amino-methylphosphine backbone. The condensations in the three-component systems primary phosphine/formaldehyde/secondary diamine with angular di(p-pheny-lene)methane spacer (or bis(4-amino-3-carboxyphenyl)methane) or with linear biphenylene spacers led to the formation of N-containing macrocyclic diphosphines 124 as a result of [2 -I- 2]-condensation (Scheme 12.48). The condensations were performed in DMF at the reagents concentrations of 0.1-0.3 M at 100-110 °C or at ambient temperature in the case of N-pyridylmethyl substituted diamines [122]. 

So it has been shown that the covalent self-assembly methodology is also effective for the synthesis of flexible cyclophane macrocyclic systems, the requirements to the building blocks geometry being not very rigid in these cases. 

Scheme 12.48 Covalent self-assembly of P,N-containing cyclophanes with aminomethylphos-phine backbone 124...

Scheme 12.51 Covalent self-assembly of macrocyclic phosphites 130-132...

Scheme 12.71 Covalent self-assembly of cyclophanes 209-210 with two l,5-diaza-3,7-diphos-phacyclooctane fragments in the basic framework...

The condensations were performed in hot DMF (110 °C) or toluene (100 °C) at the phosphine concentrations of 0.1-0.3 M and led to the cage P,N-containing cyclophanes 1-15 in good or satisfactory yields [173-179]. It indicated that the covalent self-assembly took place and this conclusion was confirmed by the NMR monitoring of the reactions which showed that they proceeded through the formation of series of intermediates and the reaction mixtures were enriched by the macrocycles only at the final steps [175]. 

Scheme 12.72 Covalent self-assembly of cyclophanes 211 with chiral intramolecular cavity...

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