Cyclizations of acetoacetates to α-acyltetronic acids

Intramolecular oxygen versus carbon alkylation of naphthoate esters. A caveat on the mechanistic aspects of neocarzinostatin chemistry

“…General procedure D (acetic acid, <5 min, 43%). NMR (300 MHz, CDCI3) : 12.21 (s, 1H, OH); 8.76 (d, 1H, 8.8 Hz); 7.90 (d, 1 , 9.0 Hz); 7.75 (d, 1H, 8.0 Hz); 7.57 (dd,1H,8.8 Hz,7.2 Hz); 7.38 (dd, 1H, 7.2 Hz, 8.0 Hz); 7.17 (d, 1H, 9.0 Hz); 6.10 (dd, 1H, 5.0 Hz, 16 Hz); 6.00 (dd, 1H, 5.0 Hz, 16 Hz); 5.04 (2£)-4-Hydroxy-2-butenyl 2-Hydroxy-l-naphthoate (36t-OH). General procedure D (acetone,<5 min,59%).…”

“…Several apparent exceptions to the rule of intramolecular oxygen alkylation are shown in Scheme V which involve reactions of 12A,'412B,15 and 12C. 16 In each of these instances, the kinetic intermediates 14A-14C would be expected to be in ready equilibrium with the starting material, thereby providing an avenue for ultimate formation of the observed carbon-alkylated adducts 13A-13C.…”

“…A bona fide example of five ring formation via kinetic intramolecular carbon alkylation of a ketone enolate involves the base-promoted cyclization of ds-allyl halide 15c (prepared in situ from the reaction of acetoacetate and the corresponding ene-1,4 dihalide).17 Treatment of this material under various conditions provides a mixture of cyclopentene 18 and vinyl cyclopropyl esters 16 in ratios which vary from 97:3 to 3:97 (only traces of the O-alkylation product 17 were isolated) (Scheme VI). Similar reaction of trazis-allyl halide 15t affords mixtures of 16 and 17, production of cyclopentene ester 18 being geometrically impossible.18 Formation of 18 from 15c is formally in accord with the Baldwin postulate of preference for a 5-(enolexo) process over one which is 5-(enol-endo).19 However, it must also be recognized that those factors which serve to insure (17) Deprés, J.-P.; Greene, A. E. J. Org.…”

Synthesis and Chemistry of Tetronic Acids

“…The base-promoted Dieckmann cyclization of glycolyl acetoacetates 4 (Scheme 1) is one of the most synthetically useful methods for the preparation of these 3-acyl derivatives. [8][9][10][11][12][13][14]26,28 The ability of these intermediates to cyclize is highly dependent on the presence of substituents at the α'-position. Thus, while the cyclization of α'-substituted glycolyl acetoacetates is a very easy process, the unsubstituted derivatives require vigorous reaction conditions to success.…”