New Oxidation of Primary & Secondary Alcohols

Oxidation reactions of primary alcohols and secondary alcohols to the corresponding aldehydes and ketones, respectively, are important reactions in organic synthesis. To date, many oxidizing agents utilizing chromium oxides such as Jones reagents, Sarett reagents, Collins reagents, and oxidizing methods using activated DMSO have been reported. Among them, the method to activate DMSO with oxalyl chloride is called Swern oxidation and is widely used as one of the most practical oxidation methods. However, the reaction temperature must be strictly controlled due to the thermal instability of the activated intermediates formed by the reaction of DMSO and oxalyl chloride in the Swern oxidation. Furthermore, because the by-product, dimethyl sulfide, has a stench, it is considered to be unsuitable for mass production.

Mukaiyama and co-workers have reported oxidation of alcohols using a sulfinimidoyl compound 1.¹⁾ According to their method, 1, nearly similar to activated DMSO in structure, oxidizes primary or secondary alcohols to the corresponding aldehydes or ketones in near quantitative yields under mild conditions.

1 reacts directly with alcohols without pre-activation to afford the corresponding carbonyl compounds. The oxidation method using 1 can be performed at room temperature without the strict control of reaction temperature required in the Swern oxidation. Moreover, the oxidation reaction is applicable to oxidation of acid-labile compounds since the reaction proceeds under basic conditions.

Catalytic oxidation of alcohols to aldehydes or ketones has also been explored. To date, the oxidation methods using tetrapropylammonium perruthenate (TPAP) and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as a catalyst have been reported and put into practical use. The oxidation method of alcohols reported by Mukaiyama and co-workers using sulfenamide 2 is one of such catalytic oxidation methods.²⁾

In this method N-chlorosuccinimide (NCS) can be used as a co-oxidant to yield the corresponding aldehydes and ketones from primary alcohols or secondary alcohols in near quantitative yields without requiring strict temperature control. The method using 2 is receiving much attention as a safe and simple catalytic oxidation method of alcohols.

Matano and his group are developing an oxidation method of alcohols using hypervalent organobismuth compounds.³⁾ This reaction progresses as shown below, and yields the desired carbonyl compounds in excellent yields.

This reaction has fairly high reactivity, and the reactions are completed at room temperature within a short period of time. Matano and co-workers are conducting comparative oxidation studies on the selectivity of the Dess-Martin periodinane and tris(2-methoxyphenyl)bismuth dichloride 3 upon conjugated alcohols and unconjugated alcohols.

According to their studies, 3 has higher selectivity over Dess-Martin periodinane upon conjugated alcohols. 3 is becoming recognized as a non-explosive, non-toxic, highly reactive and selective oxidizing agent.

Recently, Katsuki and co-workers reported that the oxidation method of alcohols using (nitrosyl)Ru-Salen complex as a catalyst. This catalyst is activated by photo-irradiation and can be used to oxidize primary alcohols to aldehydes selectively.⁴⁾