Alcohols, oxidizing reagents

DESS - MARTIN Oxidizing Reagent Oxidation of alcohols to aldehydes or ketones by means of penodinanes. 

When used at room temperature in the presence of an active platinum catalyst in an inert solvent, e.g., acetone or ethyl acetate, oxygen will oxidize nonhindered, saturated hydroxyl groups and exposed allylic alcohols. This reagent has found extensive use in sugar chemistry and is particularly suited for the selective oxidation of either 3a- or 3j -alcohols of steroids. Other hydroxyl groups on the steroid skeleton are much less sensitive to oxidation. As a result, this reaction has been used extensively in research on polyhydroxy cardiac-active principles, e.g., the cardenolides and bufadienolides, where the 3-hydroxyl group is easily oxidized without extensive oxidation or dehydration of other hydroxyl groups. The ordinarily difficult selective oxidation of the... 

Various experimental conditions have been used for oxidations of alcohols by Cr(VI) on a laboratory scale, and several examples are shown in Scheme 12.1. Entry 1 is an example of oxidation of a primary alcohol to an aldehyde. The propanal is distilled from the reaction mixture as oxidation proceeds, which minimizes overoxidation. For secondary alcohols, oxidation can be done by addition of an acidic aqueous solution containing chromic acid (known as Jones reagent) to an acetone solution of the alcohol. Oxidation normally occurs rapidly, and overoxidation is minimal. In acetone solution, the reduced chromium salts precipitate and the reaction solution can be decanted. Entries 2 to 4 in Scheme 12.1 are examples of this method. 

In order to overcome these two issues, we reversed the order of the reaction sequence, as summarized in Scheme 1.20. We took advantage of the alcohol functional group in 50. Oxidation ofpMB of 50 with DDQ proceeded smoothly to form cyclic aminal 52 (as a mixture of a and P = 11.5 1) in toluene at 0-10 °C. The resulting DDQH, which is insoluble in toluene, was filtered off, and isolated DDQH could be recycled as we demonstrated in the Proscar process (see p. 92) [32]. Thus, this process minimizes the impact to the environment from an oxidizing reagent. Cyclic aminal 52 was solvolyzed with NaOH in MeOH at 40 °C. The resulted anisaldehyde was reduced in situ to pMBOH 43 by addition of NaBH4 and the desired amino alcohol 53 was isolated by direct crystallization from the reaction mixture, upon neutralization with acetic acid, in 94% yield and >99.9% ee after crystallization from toluene-heptane. 

Such reactions are also possible in vitro, as several mild oxidizing agents are at hand nowadays. Thus, the Dess-Martin periodinane (DMP) [50] has been proven to be a versatile and powerful reagent for the mild oxidation of alcohols to the corresponding carbonyl compounds. In this way, a series of new iodine(V)-mediated reactions has been developed which go far beyond simple alcohol oxidation [51], Ni-colaou and coworkers have developed an effective DM P-mediated domino polycy-clization reaction for converting simple aryl amides, urethanes and ureas to complex phenoxazine-containing polycycles. For example, reaction of the o-hydroxy anilide 7-101 with DMP (2 equiv.) in refluxing benzene under exposure to air led to polycycle 7-103 via 7-102 in a yield of 35 % (Scheme 7.28) [52]. 

There are many ways to categorize the oxidation of double bonds as they undergo a myriad of oxidative transformations leading to many product types including epoxides, ketones, diols, endoperoxides, ozonides, allylic alcohols and many others. Rather than review the oxidation of dienes by substrate type or product obtained, we have chosen to classify the oxidation reactions of dienes and polyenes by the oxidation reagent or system used, since each have a common reactivity profile. Thus, similar reactions with each specific oxidant can be carried out on a variety of substrates and can be easily compared. 

The characteristic end point orange color can be demonstrated by addition of a slight excess of the chromic acid oxidizing reagent to a few milliliters of acetone containing a few drops of isopropyl alcohol. 

SEGPHOS [271, 272]. Using this complex as a precatalyst, transfer hydrogenation of 1,1-dimethylallene in the presence of diverse aldehydes mediated by isopropanol delivers products of ferf-prenylation in good to excellent yield and with excellent levels of enantioselectivity. In the absence of isopropanol, enantio-selective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts. Notably, enantioselective ferf-prenylation is achieved under mild conditions (30-50°C) in the absence of stoichiometric metallic reagents. Indeed, for reactions conducted from the alcohol oxidation level, stoichiometric byproducts are completely absent (Scheme 13). 

Oxidation of alcohols to carbonyl compounds is an important reaction. Stoichiometric oxidants such as chromates, permanganates and MO4 (M = Ru, Os) are the commonly used reagents [19a,59,60]. However, they are going out of favour increasingly because they create heavy metal wastes . In view of this, development of environmentally friendly heterogeneous catalysts for alcohol oxidation is very important. In the use of catalytic amounts of transition metal salts or complexes as homogeneous catalysts for the oxidation of alcohols [61-64], separation of the catalyst from the reaction mixture and its subsequent recovery in active form is cumbersome. Heterogeneous catalysts for this kind of reaction are therefore necessary [65]. Clearly, encapsulation and/or immobilization of known... 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

Common alcohol oxidation methods employ stoichiometric amounts of toxic and reactive oxidants like Cr03, hypervalent iodine reagents (Dess-Martin) and peracids that pose severe safety and environmental hazards in large-scale industrial reactions. Therefore, a variety of catalytic methods for the oxidation of alcohols to aldehydes, ketones or carboxylic acids have been developed employing hydrogen peroxide or alkyl hydroperoxides as stoichiometric oxygen sources in the presence of catalytic amounts of a metal catalyst. The commonly used catalysts for alcohol oxidation are different MoAV(VI), Mn(II), Cr(VI), Re(Vn), Fe(II) and Ru complexes . A selection of published known alcohol oxidations with different catalysts will be presented here. 

They used this new oxidizing reagent for a rapid and selective oxidation of primary and secondary benzylic alcohols to the corresponding aldehydes and ketones in good to excellent yields. BTPCP was later used for oxidation of various alkylbenzenes under neutral conditions in aqueous CH3CN to the corresponding carbonyl compounds in good yields (equation 34) °. ... 

Although difluoroenoxysilanes are typical nucleophiles, they can also react with other nucleophiles via their oxidation into radical cations. The oxidative homocoupling and the cross-coupling with heteroaromatics and alcohols proceeds very well in the presence of Cu triflate as the oxidizing reagent (Figure 2.24). " ... 

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