Alkylation of formyl ketones

Acetylenedimagnesium bromide, 66, 84, 137 Acyl-alkyl diradical disproportionations, 299 Acyl-alkyl diradical recombination, 296 Alkaline hydrogen peroxide, 10, 12, 20 Alkylation of formyl ketones, 93 Alkylation via enolate anions, 86 17a-Alkynyl steroids from 17-ketones, 67 2a-Al]yl-17jS-hydroxy-5a-androstan-3 -one, 9 5 Allylic acetoxylation, 242 Allylmagnesium bromide, 64 17 -Aminoandrost-5-en-3 -ol, 145 17 a-Aminomethy 1-5 a-androstane-3, 1718-diol, 387... 

Generally the most practical procedure for monoalkylation of steroidal ketones bearing geminal a-hydrogens is via formyl or oxalyl ketones. Some examples of the former method are described in this section. The alkylation of oxalyl ketones is described in the following section. 

Intramolecular versions of reactions other than aldols can also be considered as useful options to prepare five- or six-membered rings from their corresponding bifunctional precursors. Several examples to illustrate the diverse approaches to construct five-membered rings are given in Scheme 2.110. A high-yield method to prepare cyclopentenone 284 is given in the sequence (i) alkylation of formyl-anion equivalent 285 to give 286 (ii) Michael addition of the latter to methyl vinyl ketone (iii) removal of the carbonyl protection and (iv) intramolecular cyclization of the 1,4-diketone, 287. 

A somewhat similar method to that mentioned above involves alkylation of 4,4-dimethyl-1,3-oxathiolane 5,5-dioxide 32 at the 2 position followed by FVP at 400°C, which results in fragmentation with loss of SO2 and isobutene to give the aldehydes 33. Other electrophiles that may be used include aldehydes, ketones, and McsSiCl, making this a convenient formyl anion equivalent (79TL3375). 

The well-known reaction of a-alkyl-/3-ketoaldehydes and hydroxyl-amine has been applied to the elucidation of the structure of formyl-ation products of ketones the conclusions are, however, open to question. Some workers attempted to overcome the ambiguity of the reaction of j8-ketoaldehydes and hydroxylamine, which results in a mixture of 3- and 5-monosubstituted isoxazoles and thus considerably lowers the preparative value of the method, by using various derivatives of yS-ketoaldehydes, especially those of their enolic forms (jS-substituted vinylketones) investigated by Kochetkov et al. The use of readily available /3-chlorovinylketones (12) in the reaction with hydroxylamine represents a rather useful preparative method to synthesize monoalkylisoxazoles but again gives rise to a mixture of 3- (13) and 5-alkylisoxazoles (14). This is due to the attack... 

The most important method for the synthesis of aromatic ketones 3 is the Friedel-Crafts acylation. An aromatic substrate 1 is treated with an acyl chloride 2 in the presence of a Lewis-acid catalyst, to yield an acylated aromatic compound. Closely related reactions are methods for the formylation, as well as an alkylation procedure for aromatic compounds, which is also named after Friedel and Crafts. 

Block one side of the ketone by introducing a removable group. Alkylation takes place on the other side the blocking group is then removed. A common reaction for this purpose is formylation with ethyl formate (10-119) this generally blocks the less hindered side. The formyl group is easily removed by alkaline hydrolysis (12-41). 

Acylation of ketones having reactive methylene groups by higher esters has been shown to be an excellent method for preparing /3-diketones (method 203). If the acylating ester is an alkyl formate, then a keto aldehyde is formed (50-80%). The formylation is simply brought about by adding sodium metal to a mixture of the ketone and ester in anhydrous ether. Oftentimes, the product is isolated as the sodium salt of the hydroxymethylene form. The point of attack is unpredictable in unsymmetrical ketones, CHjCOCHjR. ... 

Alkylation + hydrogenation. The dual activity for the transformation of ketoalde-hydes by complexes of (diamine)RuCl2 with this copolymer is clearly demonstrated. Alkylation of the formyl group with organozinc reagents (e.g., Et2Zn) followed by hydrogenation of the ketone is readily accomplished. 

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