An Investigation of the Reactions of Substituted Homoallylic Alcohols with Various Oxidation Reagents

Substituted homoallylic alcohols have been synthesised both by [2,3]-Wittig rearrangement of unsymmetrical bis-allylic ethers and reaction of alkenyl chloromethyl oxiranes with Mg/THF. These substrates were then oxidized using four different oxidants. When the substituted homoallylic alcohols were oxidized with pyridinium chlorochromate or zinc chlorochromate nonahydrate the corresponding carbonyl compounds were produced. The same substrates formed the corresponding allylic oxidation products together with epoxidation products when oxidized with t-BuOOH. When and t-BuOOH and catalytic amounts of OsO4 were used the allylic oxidation reaction was prevented and the only products formed were those in which the substituted double bond was epoxidized.

almost every day. It is well known that different organic substrates can be converted into varied oxidation products depending on the type of oxidant used. For example, Zn(ClCrO 3 ) 2 ·9H 2 O (ZCC) is an oxidant which can be used under very mild conditions [1]. Pyridinium chlorochromate (PCC) will oxidize a primary alcohol to an aldehyde and stop at that stage. PCC also does not attack double bonds [2,3].
t-Butyl hydroperoxide (t-BuOOH) oxidizes olefins to epoxides and allylic oxidation products in the presence of a Cr(VI) catalyst. The allylic oxidation and the t-BuOOH decomposition are freeradical reactions, but the epoxidation is evidently not [4]. Under microwave irradiation 3Å molecular sieves promote the oxidation of secondary (linear and cyclic) and benzylic alcohols to the corresponding carbonyl compounds by t-BuOOH. Under the same conditions α,β-unsaturated alcohols are converted into α,β-epoxy alcohols in a regio-and diasteroselective manner [5]. OsO 4 can be used to oxidize alkenes to 1,2-diols (syn hydroxylation). If t-BuOOH is used with OsO 4 allylic alcohols have been converted into α,β-epoxy alcohols. Beck and Seifert have investigated the oxidation of steroidal allylic alcohols with t-BuOOH and catalytic amounts of OsO 4 [6].
Substituted homoallylic alcohols have been used in the synthesis of pheromones and antibiotics [7,8] and these compounds show very strong antimicrobial activities [9]. Various methods have been reported in the literature for the synthesis of substituted homoallylic alcohols [10][11][12][13][14][15]. The oxidation reactions of substituted homoallylic alcohols have not been investigated in detail. Therefore we have now studied the oxidation of these compounds with four different oxidation reagent systems.

Results and Discussion
When compounds 4a-d were oxidized with PCC (Method A) or ZCC (Method B) the corresponding carbonyl compounds 5a-d were formed (Scheme 1). On the other hand, 2-methyl-1,5-hexadiene-3,4-dione (6a) together with 5a was formed when 4a was oxidized with ZCC. This could be expected since ZCC in CH 2 Cl 2 is reported to be a strong oxidizing agent that oxidizes benzylic and allylic C-H bonds to give carbonyl groups [1]. Compound 6a was thus formed from oxidation of both the allylic hydrogen and hydroxyl groups of 4a.
Oxidation of 4d with PCC and ZCC produced benzaldehyde (6d), 3-Phenylpropenal (7d) and 1phenyl 1,5-hexadiene-3-one (5d). The yield of benzaldehyde formed is higher when Method A is used compared to Method B. Thus the oxidation products of 4d included small molecules (such as 6d and 7d), formed by the breakage of the bonds close to the phenyl group The oxidation of olefinic molecules containing allylic hydrogen atoms is thought to follow two possible pathways: allylic oxidation and direct attack on the double bond. When using oxygen-transfer reagent, such as t-BuOOH or H 2 O 2 and a metal catalyst, the metal can serve as a relay for the transfer of the oxygen atom from the hydroperoxide to the olefin via an oxometal intermediate. The dismutation of t-BuOOH in the presence of transition-metal catalysts to produce t-BuOH and O 2 has been documented [4]. t-BuOOH oxidizes olefins to epoxides and allylic oxidation products in the presence of a transition-metal catalyst. Catalytic epoxidation and allylic oxidation reactions follow different paths. The epoxidation is an oxygen transfer reaction (Scheme 2) while the allylic oxidation follows a free radical reaction. The epoxidation could occur via the activation of the peroxidic oxygens.

Scheme 2. The oxidation of substituted homoallylic alcohols by Methods
When the substituted homoallylic alcohols 4c,d are oxidized with t-BuOOH under OsO 4 catalysis (Method C), the substituted double bonds of 4c,d were epoxidized and no allylic oxidation products are formed. Thus, when compound 4d was oxidized by this method only the α,β−epoxyalcohol and benzaldehyde were formed.
Compounds 4c,d when oxidized with only t-BuOOH (Method D) gave allylic oxidation products and epoxidation products. The oxidation reaction of 4c,d with t-BuOOH shows completely radical character. While all the substituted-1,5-hexadien-3-ols 4a-d have allylic hydrogen and hydroxyl groups, compound 4d compound has benzylic hydrogens in addition to allylic hydrogen and hydroxyl groups. t-BuOOH thus oxidized the hydroxyl group to a carbonyl group and simultaneously one or both of double bonds were converted to an epoxide.

Acknowledgements
We are indebted to the Fõrat University Research Foundation (FÜNAF) for financial support of this work (Project number: 295)

Oxidation Reactions of Substituted Homoallylic Alcohols: Method A: Oxidation of 4a-d with PCC (General Method)
PCC (1.5 mmol) is dissolved in CH 2 Cl 2 (2 mL) and then NaOAc (0.03 mmol) is added to this solution. The substituted homoallylic alcohol (1 mmol) dissolved in CH 2 Cl 2 (15 mL) and then added dropwise to the PCC solution. After 1-2 hours, the reaction is checked by TLC to determine completion. The reaction mixture is filtered, the residues are washed with twice with ether, dried with MgSO 4 , and concentrated in vacuo give the crude product that was purified by column chromatography over silica gel.

Method B: Oxidation of 4a-d with ZCC (General Method).
A solution of substituted homoallylic alcohol (8 mmol) in CH 2 Cl 2 (70 mL) was prepared in a 200 mL round-bottomed flask equipped with a magnetic stirrer. The ZCC (16 mmol) was added in four separate portions within 15 min. with vigorous stirring. Stirring was continued for 2 hours. The mixture was diluted with CH 2 Cl 2 (120 mL) and filtered. The filtrate was evaporated on a rotatory evaporator under reduced pressure.

Method D: Oxidation of 4c,d with t-BuOOH
Oxidation of compounds 4c and 4d with t-BuOOH is described in Method C. In this method the OsO 4 was omitted.