Acyclic and cyclic unsymmetrical ketones 1 are regioselec-phenyl isothiocyanate as acylating agents. Subsequent acidic tively acylated via their corresponding metalated dimethyl-hydrolysis leads to the 1,3-diketones 6 in acceptable to excelhydrazones 3 by using acid chlorides or anhydrides, arylni-lent overall yields. The tautomeric structure of the product triles, ethyl formate, carbon disulfide/methyl iodide, alkyl hydrazones 4, 5, ?, and 8 is determined. Cyanation of 3 with chloroformates, dialkyl carbonates, phenyl isocyanate, or cyanogen bromide affords the a-cyano dimethylhydrazones 9. However, it is a well-known fact that 1 : 1 acylations of metal enolates are associated with various problems, such as 0-and diacylations, proton exchange between the enolate and the acylation product and thus low yields, as well as the formation of regioisomers[341. To circumvent these problems, several alternatives have been developed as, for instance, the strict control of reaction condition~[~'] or the use of indirect methods by employing e n a m i n e~ [~~-~~I , enaminosilanes['"'l, silyl We now wish to report the experimental details of an efficient and regioselective 1 : 1 acylation of ketones to 1,3-diketones with acid chlorides, acid anhydrides, esters, arylnitriles and dialkyl carbonates based on the dimethylhydrazone method[471.
Results and DiscussionMetalated dimethylhydrazones (DMHs) have proven to be versatile enolate equivalents in a variety of electrophilic substitutions a to the carbonyl group of aldehydes and ke-[*I Alexander von Humboldt fellow, University of GieDen, 1980, Universit of Bonn, 1980, 1983, and RWTH Aachen, 1991. -y+*l Part of the Diplomarbeit of P. W., University of GieDen, 1978.tones, and problems of classical carbonyl chemistry mentioned above could be solved efficiently[471. This turned out to be true also in acylation reactions by employing a great variety of acylating electrophiles. As depicted in Scheme 1, cyclic and acyclic, mainly unsymmetrical, ketones 1 were converted into their corresponding dimethylhydrazones 2, which in turn were metalated with n-butyllithium in tetrahydrofuran (THF) at -78 "C (methyl ketone DMHs) or lithium diisopropylamide (LDA) at 0°C to yield the lithiated species 3. The T H F suspension of the azaenolates 3 thus obtained was then added to a solution of the acylation reagent (acid chloride, anhydride, ester, or arylnitrile) in THF at -78 "C, which after quenching and workup resulted in the formation of the acylated hydrazones 4 and 5, respectively. Finally, 4 and 5 were dissolved in methanol and hydrolyzed with 2 N HCI under heating to the desired 1,3-diketones 6, which are thus available in a regioselective way and with acceptable to excellent overall yields (see Experimental).When the lithiated DMHs 3 were trapped with acid chlorides, ethyl formate, or acid anhydrides, the hydrazones 4[481 were obtained, which according to the spectroscopic data (IR, 'H and 13C NMR) in the cases of R2 = H (4a-f,m) entirely exist as the keto-enehydrazine tautomers 4A. The...
