Alkyl radicals, geometry

Lott WB, Chagovetz AM, Grissom CB. Alkyl radical geometry controls geminate cage recombination in alkylcobalamins../ Am Chem Soc 1995 117 12194-201. 

From a synthetic point of view, the regioselectivity and stereoselectivity of the cyclization are of paramount importance. As discussed in Section 11.2.3.3 of Part A, the order of preference for cyclization of alkyl radicals is 5-exo > 6-endo 6-exo > 7-endo S-endo > 1-exo because of stereoelectronic preferences. For relatively rigid cyclic structures, proximity and alignment factors determined by the specific geometry of the ring system are of major importance. Theoretical analysis of radical addition indicates that the major interaction of the attacking radical is with the alkene LUMO.321 The preferred direction of attack is not perpendicular to the it system, but rather at an angle of about 110°. 

For a long time, this knowledge on carbon-centred radicals has driven the analysis of spectroscopic data obtained for silicon-centred (or silyl) radicals, often erroneously. The principal difference between carbon-centred and silyl radicals arises from the fact that the former can use only 2s and 2p atomic orbitals to accommodate the valence electrons, whereas silyl radicals can use 3s, 3p and 3d. The topic of this section deals mainly with the shape of silyl radicals, which are normally considered to be strongly bent out of the plane (a-type structure 2) [1]. In recent years, it has been shown that a-substituents have had a profound influence on the geometry of silyl radicals and the rationalization of the experimental data is not at all an extrapolation of the knowledge on alkyl radicals. Structural information may be deduced by using chemical, physical or theoretical methods. For better comprehension, this section is divided in subsections describing the results of these methods. 

Table 1.1 shows that the nature of the a-substituent in the radical centre enormously influences the Si hfs constants. These constants, which can be used as a guide to the distribution of unpaired electron density, were initially correlated to changes in geometry at the radical centre by analogy with C hfs constants of a-substituted alkyl radicals. Indeed, it was suggested that by... 

Alkyl radicals exhibit trigonal planar geometry. 

To summarize the considerable available structural data with respect to fluorine substitution, one can conclude that non-conjugated carbon radicals bearing at least two fluorine substituents will be strongly pyramidal, a-radicals, while //-fluorine substituents appear to have little influence on the geometry of a radical. The strong a-character of CF3, CHF2, and perfluoro-n-alkyl radicals has a considerable influence on their reactivity. 

If an attempt were made to apply the rules of valence shell electron pair repulsion theory to radicals, it would not be clear how to treat the single electron. Obviously, a single electron should not be as large as a pair of electrons, but it is expected to result in some repulsion. Therefore, it is difficult to predict whether a radical carbon should be sp2 hybridized with trigonal planar geometry (with the odd electron in a p orbital), sp3 hybridized with tetrahedral geometry (with the odd electron in an sp3 AO), or somewhere in between. Experimental evidence is also somewhat uncertain. Studies of the geometry of simple alkyl radicals indicate that either they are planar or, if they are pyramidal, inversion is very rapid. 

FIGURE 11.1 Geometries of n-bromopropane, primary, secondary, and tertiary alkyl radicals. Parameters are calculated at the MP2(full)/6-31G(d) level of theory. 

Most of the chemistry that is discussed in this chapter involves alkyl radicals ( CR3). The alkyl radical is a seven-electron, electron-deficient species. The geometry of the alkyl radical is considered to be a shallow pyramid, somewhere between sp2 and sp3 hybridization, and the energy required to invert the pyramid is very small. In practice, one can usually think of alkyl radicals as if they were sp2-hybridized. 

Marks and co-workers (12) have studied the alkyl substituted compounds 7-16. Assuming that INDO/2 molecular orbital calculations on alkyl radicals can reasonably predict experimental electron-nuclear hyperfine coupling constants, a, they have calculated the a values for each of the alkyl substituents. Taking the ratio of the contact shifts of the ortho positions in 7 and vinylic position in 16 as equal to the ratio of calculated a values and the ratio of the geometry factors as equal to the ratio of pseudocontact shifts, Marks and co-workers could solve for the contact and pseudocontact shifts in 7 and 16. Factoring the... 

With this information in hand, it seemed reasonable to attempt to use force field methods to model the transition states of more complex, chiral systems. To that end, transition state.s for the delivery of hydrogen atom from stannanes 69 71 derived from cholic acid to the 2.2,.3-trimethy 1-3-pentyl radical 72 (which was chosen as the prototypical prochiral alkyl radical) were modeled in a similar manner to that published for intramolecular free-radical addition reactions (Beckwith-Schicsscr model) and that for intramolecular homolytic substitution at selenium [32]. The array of reacting centers in each transition state 73 75 was fixed at the geometry of the transition state determined by ah initio (MP2/DZP) molecular orbital calculations for the attack of methyl radical at trimethyltin hydride (viz. rsn-n = 1 Si A rc-H = i -69 A 6 sn-H-C = 180°) [33]. The remainder of each structure 73-75 was optimized using molecular mechanics (MM2) in the usual way. In all, three transition state conformations were considered for each mode of attack (re or ) in structures 73-75 (Scheme 14). In general, the force field method described overestimates experimentally determined enantioseleclivities (Scheme 15), and the development of a flexible model is now being considered [33]. 

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