Oxidation of active methylene groups

The oxidation of active methylene groups by periodate both in acyclic... 

Periodate oxidation of activated methylene groups (ArCHRC02H -> ArCOR)... 

The analogous oxidation of active methylene groups formed during the oxidation of a variety of carbohydrates by periodate has been considered in detail.22... 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

OXIDATION WITH p-NITROSODIMETHYLANILINE Oxidation of Activated Methylene Group to Carbonyl [986]... 

Riley oxidations. Oxidations of organic compounds with selenium dioxide, e.g., the oxidation of active methylene groups to carbonyl groups. 

Oxidation of activated methylene groups can provide convenient access to carbonyl compounds which are otherwise difficult to prepare. Thus, t-butyl hydroperoxide and catalytic... 

Scheme 3.8 Green, clean, and selective oxidation of activated methylene groups to ketones.

In certain condensation reactions hydrogen may be replaced by oxygen, with interchange of the oxidation states of the carbon atoms that are to be bonded to one another. In such cases it is particularly nitroso compounds and derivatives of nitrous acid that serve as oxidant with active methylene groups they form Schiff bases or oximes, which afford the oxo compound on hydrolysis. 

Periplanone B is the most active sex pheromone found in the alimentary tract and excreta of the American cockroach Periplaneta americana. An elegant total synthesis of this germacrane sesquiterpene was achieved by SCHREIBER and SANTINI Cyclodecatrienone 1 is an obvious precursor. One of the oxirane rings arises from epoxidation of the enone CC double bond, the other from [2-1-1]-cycloaddition of a carbene to the carbonyl bond of the enone. Oxidation of the methylene group introduces the additional carbonyl double bond. The CC double bond of the enone results from an elimination of HX in the a-X-substituted cyclodecadienone 2, which, on its part, is feasible by substitution of cyclodecadienone 3. An electrocyclic opening of the cyclobutene ring in 4 provides the 1,3-diene substructure in 3. 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

This variation provides a regiospecific synthesis of isoxazoles with a great variety of substituents. The nitrile A-oxide does not react with the doubly activated methylene group in neutral or acidic medium, but under alkaline conditions the reaction proceeds exother-... 

At elevated temperatures in the presence of oxygen the aluminium oxide layer catalyzes the formation of blue fluorescent aluminium oxide surface compounds with 4-hydroxy-3-oxo-A -steroid structures [4]. Aluminium oxide acts as an oxidation catalyst for an activated methylene group. 

Conventional conversion of amide, lactam, imide, and urea carbonyl groups into enaminones, enamino esters, or enamino nitriles requires prior activation of the carbonyl groups either by alkylation to imino ethers, followed by reaction with activated methylene groups, or by thiation, e.g. with P2S5, to thiocarbonyl groups followed by alkylation (and possibly also oxidation), and, again, subsequent reac-... 

The oxidation of an activated methylene grouping is somewhat slower than the other periodate reactions.14 Sprinson and Chargaff89 found that... 

Nickel halides and nickel complexes resulting from oxidative addition can also give rise to subsequent replacement and insertion reactions. Replacement reactions have been described mainly with arylnickel halide complexes (examples 23, 29, and 31, Table III). Carbanionic species replace halide ions and can undergo coupling or insertion reactions. An example of application of a carbanionic reaction to the synthesis of a natural product is the coupling step between an aromatic iodo-derivative and an active methylene group to form cephalotaxinone (example 23, Table III). 

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