Keto ethers, formation

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

The reductive ether formation from keto epoxides is an acid-catalyzed process (Eqs. 234407 and 235408). 

The review starts with a discussion of the mechanism of keto-enol tautomerisation and with kinetic data. Included in this section are results on stereochemical aspects of enolisation (or enolate formation) and on regioselec-tivity when two enolisation sites are in competition. The next section is devoted to thermodynamic data (keto-enol equilibrium constants and acidity constants of the two tautomeric forms) which have greatly improved in quality over the last decade. The last two sections concern two processes closely related to enolisation, namely the formation of enol ethers in alcohols and that of enamines in the presence of primary and secondary amines. Indeed, over the last fifteen years, data have shown that enol-ether formation and enamine formation are two competitive and often more favourable routes for reactions which usually occur via enol or enolate. 

Why must the diketone tautomerize to the keto-enol before the addition of EtOH can occur By the principle of microscopic reversibility, both enol ether formation and enol ether hydrolysis must proceed by the same sequence of steps (only in reverse of one another). Protonation of the enol ether, the first step in its hydrolysis, would certainly occur on the carbonyl O, not on C, so enol ether formation must proceed through the same intermediate. 

The laser jet system of irradiation allows the observation of multi-photon processes and is becoming more popular. Under these conditions, the keto ether (35) in carbon tetrachloride solution undergoes two processes to give 4-phenyl-benzaldehyde (one photon) and 4-phenylbenzyl chloride (two photons), while from ethanol solutions of (35), evidence is obtained to suggest that the formation of the ether (36) arises from a three-photon process (Adam and Schneider). 

Chemistry of the Tricyclic Diterpenoids.— The conversion of virescenol A (66 R = OH) into virescenol B (66 R = H) was complicated by the ease of 2,19-ether formation. In the event the transformation was achieved through hydro-genolysis of the keto-furan (67). The chirality of nucleophilic reactions at the C-4 axial aldehydes and methyl ketones has been examined in the podocarpane series. The reaction of some ring B enol-acetates with thallium(l) acetate and iodine has been studied.lodination at the 6a-position is followed by elimination to form a/8-unsaturated ketones. 

As discussed earlier (see also Chapter 6), oxime derivatives are often prepared for polyfunctional compounds containing ketone groups in order to prevent the formation of mixed enol-silyl ethers. An alternative approach is to use a catalyst to enhance the yield of enol-silyl ethers (see also above. Section 4.2.3, for TMS ethers). The use of potassium acetate in toluene as catalyst is reported to produce a quantitative yield of TBDMS ethers and >96% yield of TBDMS-enol ethers of a, -unsaturated keto steroids [326]. An alternative to this approach, set out below, uses sodium formate to catalyse enol-silyl ether formation with fewer by-products being produced [12, 13]. 

The configuration of a keto-ether (301 R = OMe) obtained in 28% yield on methanolysis of the diazoketone (301 R = Nj) has been shown to have the i -glycero-ii-galacto configuration, rather than the d- or. -glycero- j-altro configuration previously suggested by c.d. (see Vol. 8, p. 135), by formation of the AT-acetyl-lincosamine derivative (302) and its C-6 epimer. ... 

Benzisoxazoles, also called anthranils as derivatives of anthranilic acid, are most commonly formed by the closure of bonds C(l)—C(2) or C(2)—C(3), or the introduction of atom C(3) resulting in formation of bonds C(2)—C(3) and C(3)—C(3a). As with the 1,2-benzisoxazole series, many early structural ambiguities were present in assignments (67AHC(8)277, 62HC(17)1, 66Dis(B)102). The 3-hydroxy compound is primarily in the keto form and only recently have ethers been reported. 

The reaction can be performed under a variety of conditions. Origin-aiiyi2o,i26,234 acetylene and potassium in liquid ammonia were used. Subsequently, this was simplified by the use of potassium r-amylate in r-amyl alcohol and later this system was found to react selectively at C-17 in the presence of an A-ring a,j5-unsaturated ketone. A closer investigation of these reaction conditions revealed the formation of a small amount (2-3 %) of the disubstituted acetylene this can be avoided by reacting the 17-keto steroid with acetylenedimagnesium bromide in ether-tetrahydrofuran (see chapter 10.)... 

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