Isopropyl radical addition effect

Next, the effects of varying the stereocontrol elements on the oxazolidinone moiety were assessed, with the main goal to examine the change in diastereoselectivity. Without optimizing for yield, isopropyl radical additions to several N acylhydrazones 8a 8e (See Scheme 2.1 for structures) were compared for stereo selectivity (Table 2.4). Although the measurement was not available for 8c, all auxiliaries gave very high diastereoselectivity in addition of isopropyl radical to propionaldehyde hydrazone [24b]. 

Table 2.4 Effect of different stereocontrol elements on diastereoselectivity in isopropyl radical addition.

Prototypical radical additions were examined under manganese-mediated photolysis conditions with InCp as the Lewis acid, coupling isopropyl iodide with a variety of y-hydrazonoesters 35a-35d (Table 6) bearing varied substitution at the position a to the ester. The a-methyl, a,a-dimethyl, and a-benzyloxy substituents appeared to have little effect on reaction efficiency and selectivity, as all provided the isopropyl adducts with consistently high diastereoselectivities and excellent yields (91-98%). Surprisingly, the selectivity was only slightly... 

The effects discussed unfortunately are not mutually exclusive since the reagents used as hydrido complex scavengers also trap radicals. Nevertheless, the results obtained by using these additives help to establish the isopropyl radical and hydrido complex as intermediates in the reaction. 

The diphenylmethyl oxazolidinone proves to be effective in promoting selective additions of radicals to unsymmetrical fumarates 21 [25]. Thus, addition of isopropyl radical to 16 proceeds regioselectively, addition to the carboethoxyl side of the alkene being favored in the absence of Lewis acid 22/23 = 11 1. Diaster-eoselectivity for formation of 17 in the absence of Lewis acid was poor, about 1.6 1. Several lanthanide and prelanthanide Lewis acids used stoichiometrically improve... 

The cumulative effects of multiple substituents have been studied at length in search of particularly stable radicals. It is generally found that the repetitive addition of identical substituents leads to a stepwise decrease in RSE values. This is well illustrated by the comparison of the methyl, ethyl, isopropyl, and ferf-butyl radicals with RSE values of 0.0, - 13.8, - 23.3, and - 28.3 kj/mol. Thus, while the stability of the alkyl radicals clearly increases with the number of alkyl substituents attached to the radical center, the substituent ef-... 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

Efforts to develop a y amino acid synthesis in which the oxidation state need not be adjusted after coupling led to the hypothesis that y hydrazonoesters may be com petent radical acceptors. Would the stereocontrol model be applicable in the presence of an additional Lewis basic ester function in the hydrazone. This question was addressed via prototypical Mn mediated photolytic conditions with InCla as the Lewis acid. Successful coupling was achieved between isopropyl iodide and a variety of y hydrazonoesters 52a S2d (Table 2.7, entries 1 4) bearing methyl, dimethyl, and benzyloxy substituents at the position (1 to the hydrazone (a to the ester). Consistently high diastereoselectivities and excellent yields (91 98%) of the isopropyl adducts S3a S3d indicated that the substitution patterns examined in this study had little effect on reaction selectivity and efficiency. 

Since much of the methane yield appears to be produced via methyl radicals, the yield should be affected by propylene concentration. We found little effect below 1 mole % propylene but the yield fell by 20% as the propylene concentration increased to 10 mole %, both in the presence and absence of SFe. These results, however, do not indicate how much methane is formed from CH3 precursors and how much by molecular processes. The effect of propylene is being studied further in an attempt to obtain this information. The electron scavengers appear to increase the methane yield slightly. Since they do not decrease the yield, this probably means that electron-positive ion neutralization does not produce methane. The reason for the increase in G(CH4) is not clear but it could occur if ion-ion neutralization produced methane, or if some physical interaction caused a transfer of energy from the additives to isopropyl alcohol. The slight increase in CH4 yield with SF concentration tends to favor the latter assumption. 

We have established by additional unpublished research that 2-propanol increases G(Ce ) from 2Gh202 Gh — Goh to 2GH2O2 Gh + G0h- This effect of isopropyl alcohol is consistent with a reaction mechanism which is similar to that proposed for the effects of thallium (I) (24) and formic acid (26, 27) on G(Cem). The OH radical reacts with isopropyl alcohol to yield an intermediate which reduces cerium (IV) ... 

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