Isopropyl radical addition

The methyl radical adds to the terminal carbon of propadiene (la) with a rate constant fc= 1 x 104 M-1 s-1 [27]. This elementary reaction requires an activation energy of 34 kj mol-1 based on an Arrhenius analysis of data recorded in the temperature range 100-210 °C. Comparable results were obtained for ethyl and isopropyl radical addition to substrate la (Table 11.3) [27]. 

Diastereoselectivity in radical additions to hydrazones 3 and 7 proved to be quite promising, with diastereomer ratios ranging from 93 7 to 99 1 (Table 3) [47]. In search of optimal stereocontrol, substituents on the oxazolidinone moiety were varied. Thus, isopropyl radical additions to several /V-acylhydrazones 3a-3e were compared for stereoselectivity (Scheme 3). High diastereoselectivities were observed in all adducts 13a-13e, although a rigorous measurement was not obtained on 13c. All of the auxiliaries impart stereocontrol suitable for practical synthetic application [48],... 

Scheme 3 Role of oxazolidinone substituents on diastereoselectivity in isopropyl radical addition...

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]. 

When )3-scission can occur in the radical, further reactions compete with acid amide formation. Thus oxaziridine (112) with iron(II) ion and acid yields stabilization products of the isopropyl radical. If a-hydrogen is present in the Af-alkyl group, radical attack on this position in (113) occurs additionally according to the pattern of liquid phase decomposition. 

Shevlin and coworkers30 studied the radiolysis-induced addition of the a-hydroxy isopropyl radical to substituted 1,6-heptadienes and analogs containing a heteroatom. The radical was generated by /-irradiation of propanol solutions of various 1,6-heptadienes. It was found that the adduct to the double bond decomposed to give a compound containing a five-membered ring (equation 26). 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

Chilton and Gowenlock85,87 pyrolyzed (z -C3H7)2Hg with NO and N2 as a carrier gas in a flow system at 230-280°C. They found (CH3)2 CHN=0 and (CH3)2C=NOH as products,85 the latter arising from the isomerization of the former. Woodall and Gunning454 studied the sensitized [Hg 6(3.Pi) plus NO Ilj)] decomposition of propane and its deuterated analogs at room temperature. Both n-propyl and isopropyl radicals were produced and added to NO. The product isomers, i.e., the respective oximes, were the principal products. An unusual feature of this study was that the oximes were formed readily at room temperature. The authors suggested that the reactant radicals might have been hot, and this coupled with the heat of addition could have facilitated the isomerization. 

Vaughan et al. (103) studied the photobromination of ethylene, propylene, 1-butene, isobutene, and vinyl chloride in the gas phase and found in every case where a distinction could be made that the product was almost entirely the so-called abnormal addition product in terms of the Markownikoff s rule. However, the more recent work of Skell et al. (95) shows that 2-bromo-w-propyl radical may rearrange very rapidly to 1-bromo-isopropyl radical. In view of this the observed exclusive terminal addition of Br atoms in the case of propylene could be in part due to rapid rearrangement. 

When the same kind of reaction is carried out in the presence of a Lewis acid, instead of intramolecular hydrogen bonding, the formation of addition product with high diastereoselectivity can be achieved [18-23]. Eq. 10.10 shows the chiral addition of an isopropyl radical to Lewis acid-chelated chiral a,(3-unsaturated-A-enoyloxazolidinone 6-membered rigid ring [IY] in the presence of Lu(OTf )3 (Tf = CF3S02). 

The first test of the chiral /V-acylhydrazones was in tin-mediated radical addition [47,48]. Addition of isopropyl iodide to propionaldehyde hydrazone 3a was chosen for initial screening (Scheme 2). Using the tin hydride method with triethylborane initiation [51, 52] (Bu3SnH, Et3B/02), with InCl3 and ZnCU as Lewis acid additives, desired adduct 13a was obtained with high diastereoselectivity. In contrast, 13a was produced with poor selectivity (diastereomer ratio, dr 2 1) in the absence of Lewis acid. 

Because disconnection of a-alkoxy-y-amino acid 28 calls for (3-alkoxyhydra-zone 30, the potential for (3-elimination of the alkoxy group from the hydrazone precursor 30 (Scheme 7) makes non-basic conditions critical. In fact, treatment of 30 with TBAF in THF led to just such a (3-elimination (Marie, University of Iowa, unpublished). However, the manganese-mediated radical addition of isopropyl iodide proceeded in 77% yield, without any evidence of (3-elimination, to afford 31 as a single diastereomer. Reductive removal of the chiral auxiliary and oxidation to the carboxylic acid gave 28 in good overall yield [103]. 

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... 

Terpenoid Synthesis from Isoprene.—Interest continues in new syntheses of iso-prene and its derivatives the dioxan (37) is obtained108 in good yield by the Prins reaction of methylallyl chloride with formaldehyde (cf. Vol. 5, p. 8) free-radical addition of isopropyl alcohol to vinyl acetate yields compound (38) which gives isoprene by acid-catalysed reaction over alumina.109 (Z)-2-Methylbut-2-en-l-ol and dimethylallyl alcohol are readily available from frans-crotyl alcohol.110... 

The e.s.r. spectrum of a deposit formed by the deposition of hydrogen atoms on propylene in a matrix of adamantane is shown in Fig. 18. Comparison with the spectra of the two possible product radicals, n-propyl and isoprop3d, shows clearly that addition has occurred almost exclusively to the terminal CH2-group to form the isopropyl radical. The possibility that a small amount of n-propyl radical is present cannot be ruled out, but from an analysis of the e.s.r. spectrum it is conservatively 3... 

Fig. 18. First derivative e.s.r. spectra in adamantane of (a) isopropyl radical, (b) radical formed by addition of H-atoms to propene, and (c) n-propyl radical.

The mechanism of this addition involves the conjugate addition of the isopropyl radical to... 

---