Remote functionality effect

The new finding of the remote functionality effect on the sialyl donor property has given rise to a variety of C5-modified sialyl donors 101-104 (O Scheme 29). 

McNaughton, B. R. Bucholtz, K. M. Camaano-Moure, A. Miller, B. L. Self-selection in olefin cross metathesis The effect of remote functionality. Org. Lett. 2005, 7, 733-736. 

Generally, hypervalent iodine reagents are often better than traditional reagents of similar reactivity, with respect to efficiency and chemoselectivity - sometimes even stereoselectivity. Unusual reactivity is another interesting feature which has often resulted in unexpected transformation. Examples of such reactions may be found in the oxidation of nitrogen-containing compounds, the Hofmann rearrangement in acidic conditions, the acetalization of carbonyl compounds in alkali, the remote functionalization of steroids, etc. Some unique transformations were effected in the... 

Nevertheless, some notable effects have been observed in the metal-mediated activations of alkanols with larger alkyl backbones, where dehydration still persists but activation of internal C-H bonds via remote functionalization also becomes accessible. Thus, regiospecific 3,4-dehydrogenation of l,6-hexandiol/Fe+ [31] is associated with a considerable diastereoselectivity (an SE of about 3.2 can be derived from the experimental data). Similarly, 3,4-dehydrogenation of 1,8-oc-tandiol/Fe+ occurs diastereoselectively [32]. Note, however, that most complexes of the monofunctional alkanols 13 and 16 with Mn+-Co+ show negligible SEs. 

A recent report by Miller and coworkers investigated the effects of remote functionality on the efficiency and stereochemical outcome of the olefin metathesis reaction [55]. Using a series of allyl- and homoallylamides, they demonstrated that both the yield of self-metathesis products and the ratio of cis- and trans-olefin isomers formed were strongly dependent on remote functionalities. Although it does not preclude the use of olefin metathesis in DCC experiments, it is an important factor that needs to be considered when designing olefin-based DCLs. Indeed, in an ideal scenario, one would expect the course of the reaction and product distribution in a DCL to be relatively insensitive to functionality remote from the reacting centers, which is unfortunately rarely the case. 

In a more conventional ligand design, Ros et al. used chiral A -tra 5-2,5-diphenylpyr-rolidinyl imidazole as the starting point to introduce a thioether functionality on a primary alkyl halide carrier (see Figure 4.85) [261], The thioether functionality becomes chiral upon coordination to palladium and the remote chirality effect of the other, the pyrrolidine wingtip group ensures that only one of the two possible sulfur based enantiomers is realised. 

On the basis of this molecular level picture, Rebitsky et al. constructed a corrqrlete kinetic model of the remote control effect in selective oxidation, including transient effects (32). This predicts isothermal bistability in certain conditions. Such bistabilities have been found experimentally in a special reaction (33). For a catalyst of composition (by weight) Rm = acceptor/(acceptor+donor), the model gives the fraction a of Ae potentid sites which are redly active as a function of the reaction conditions (hydrocarbon and oxygen pressures, pnc and P02 respectively, temperature T and time t). 

Remote Functionalization C-H Activation. Substituted 7V (alkoxy)thiazolethiones have been applied in selective C-EI activation reactions. For example, 5-bromohydrins that serve as starting materials for succeeding polar transformations have been prepared from 7V-(l-pentyloxy)-5-(jO-methoxyphenyl)-4-methyl-thiazole-2(3//) thione and BrCCl3 (eq 8). This reaction is preferentially conducted under thermal conditions since the effectiveness of the underlying 1,5-hydrogen translocation benefits from elevated temperatures. ... 

Morton TH and Beauchamp JL (1975) Chainlength effects upon the interaction of remote functional groups. Journal of the American Chemical Society 97 2355- 2362. 

Both Crimmins and Siliphaivanh, as well as Cossy et al., utilized the catalytic base-promoted conjugate addition in the total synthesis of leucascandrolide A. Crimmins first reported on the cyclization of alcohol 17 to provide the A ring THP 18 in very good yield (80 %) and a dr of 12 1 (Scheme 5) [23]. In 2007, Cossy described the same reaction using a very similar substrate to provide the 2,6-cis disubstituted THP with low diastereoselectivity (dr = 3 1) [24]. These examples clearly illustrate the subtle effects that remote functionality bears on stereoselectivity. 

In the main, the physical and chemical properties of saturated and partially unsaturated alicyclic compounds closely resemble those of the analogous acyclic compounds formally derived by cleavage of the carbon ring at a point remote from any functionality. Relatively small, but often significant, differences in properties arise from conformational effects, and from strain effects in small rings, and these differences can be striking in properties which are particularly sensitive to molecular shape. 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

Some olefinic molecules have a second function that anchors itself on the catalyst surface in such a way so as to enforce addition of hydrogen to its own side of the molecule. This anchoring effect, dubbed haptophilicity 112,113), has been observed by many investigators 0,19,74,78,90,120). An example of Gula and Spencer 47) illustrates how the anchoring tendencies of a function remote from the point of saturation may influence the stereochemistry. 

This chemistry becomes synthetically useful when one of the isomeric palladium intermediates can react with a neighboring substituent and the other isomer cannot. Thus, we have taken advantage of this effect to synthesize a range of polycyclic aromatic hydrocarbons by Pd migration and subsequent arylation (Scheme 24).21 This provides a unique way to form new carbon-carbon bonds in a location remote from the original functionality. 

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