Oxygenation base-catalyzed

Oxidation of amines to amides. It is usually difficult to oxidize selectively the a-methylene group of an amine to obtain the corresponding amide. However, arylmethylamines (2) condense with 1 to afford 3 in satisfactory yield. Base-catalyzed oxygenation of 3 results in amides (4) with regeneration of 1. Two conditions for oxygenation can be used. Potassium f-butoxide in t-butanol gives 4 in 36-85% yield, but 1 is recovered in only 10% yield (1 is unstable under these conditions). Alternatively, the combination of KOH in ethanol leads to 4 in 15-79% yield with better recovery of 1 (70%). ... 

Nishinaga has studied the base-catalyzed oxygenation of tert-butylated phenols63 64). In methanol, ethanol, or 2-propanol containing KOH, the oxygenation of 1 at 0 °C gave rise to the corresponding p-hydroperoxides 2 in nearly quantitative yields. 

Base-catalyzed oxygenation of 2,6-di-t-butylphenols (in which oxidative coupling is hindered) in alkaline alcohol solution yields 2,6-di-t-butyl-4-hydroperoxy-2,5-cyclohexadienones [8-10] ... 

Base-catalyzed oxygenation of 3,5-DTBC in 75% aqueous methanol at pH 9-11 affords 12, 13 and 14 [27]. In the presence of divalent metal ions, the only product is 12, while under UV or visible irradiation in methanol, the sole product is 15. 

Similarly to the base-catalyzed oxygenation of phenols (see Chapter 5.1. ), dioxygen attacks the keto-tautomer 18 to give peroxide 19, which transforms to cleavage products ... 

As cobalt complex-mediated oxygenation of these hindered phenols (11) occurs 30 times faster than base-catalyzed oxygenation 62), the phenolato Co(III) complex (12) evidently possesses special activation for reaction with molecular oxygen. In keeping with the desirability of a localized, soft anionic center in an oxygenase substrate, we can only assume that the metal is able to localize the n-anionic charge into an orbital with more [sp ] character. 

Nishinaga, a., T. Shimizu, and T. Matsuura Reaction of Potassium Superoxide with Phenoxy Radicals. On the Mechanism of Base-Catalyzed Oxygenation of Phenols. Chem. Letts 1977, 547. 

Nishinaga, A., T. Shimizu, and T. Matsuura Base-catalyzed Oxygenation of tert-Butylated Phenols 3. Base-catalyzed Reaction of Peroxyquinols Derived from Oxygenation of 2,6-Di-tert-butylphenols and Mechanism of Regioselective Formation of Epoxy-o-quinol from 2,4,6-Tri-tert-butylphenol. J. Org. Chem. 44, 2983 (1979). 

The mechanism of this reaction is outlined m Figure 17 8 It is analogous to the mech anism of base catalyzed hydration m that the nucleophile (cyanide ion) attacks the car bonyl carbon m the first step of the reaction followed by proton transfer to the carbonyl oxygen in the second step... 

The proton transfer equilibrium that interconverts a carbonyl compound and its enol can be catalyzed by bases as well as by acids Figure 18 3 illustrates the roles of hydroxide ion and water m a base catalyzed enolization As m acid catalyzed enolization protons are transferred sequentially rather than m a single step First (step 1) the base abstracts a proton from the a carbon atom to yield an anion This anion is a resonance stabilized species Its negative charge is shared by the a carbon atom and the carbonyl oxygen... 

The slow step m base catalyzed enolization is formation of the enolate ion The second step proton transfer from water to the enolate oxygen is very fast as are almost all proton transfers from one oxygen atom to another... 

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

Mechanism of Base-Catalyzed Hydration The base-catalyzed mechanism (Figure 17.5) is a two-step process in which the first step is rate-detennining. In step 1, the nucleophilic hydroxide ion attacks the carbonyl group, forming a bond to carbon. An alkoxide ion is the product of step 1. This alkoxide ion abstracts a proton from water in step 2, yielding the geminal diol. The second step, like all other proton transfers between oxygen that we have seen, is fast. 

Mechanism of base-catalyzed enol formation. The intermediate enolate ion, a resonance hybrid of two forms, can be protonated either on carbon to regenerate the starting keto tautomer or on oxygen to give an enol. 

Reactions 16-38-16-49 are base-catalyzed condensations (though some of them are also catalyzed to acids). In 16-38-16-47, a base removes a C—H proton to give a carbanion, which then adds to a C=0. The oxygen acquires a proton, and the resulting alcohol may or may not be dehydrated, depending on whether an a hydrogen is present and on whether the new double bond would be in conjugation with double bonds already present ... 

Similar to the thermal rearrangements discussed in the previous subsection, the base-catalyzed rearrangements of cyclic four-membered sulfones to five-membered sulfinates have also been reported. For example, Dodson and coworkers have observed the rearrangement of cis- and trans-2,4-diphenylthiethane 1,1 dioxides to cis- and trans-3, 5-diphenyl-1,2-oxathiolane (2,3)-cis-2-oxides, respectively (equation 35), on treatment with t-butoxymagnesium bromide, which is stereospecific with respect to the phenyl group but stereoselective with respect to the oxygen atoms on sulfur. 

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