Tetronic acids, protection

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Methoxyethoxymethyl, 365 Enamino Derivatives, 365 4-Methyl-1,3-dioxolanyl Enol Acetate, 365 Pyrrolidinyl Enamine, 365 Benzyl Enol Ether, 366 Butylthio Enol Ether, 366 Protection of Tetronic Acids, 366 Trimethylsilyl Enol Ether, 367... 

Duffield, J.J. and Regan, A.C. (1996) Asymmetric synthesis of tetronic acids by Blaise reaction of protected optically active cyanohydrins. Tetrahedron Asymmetry, 7, 663-666. 

Ally] esters (R2 = CH2C(R3)=CH2) could be transformed to the corresponding 3-allyltetronic acids by maintaining microwave irradiation at 120 °C for 60 min [59]. However, cleavage of the tetronic acids under the above mentioned conditions remained somewhat troublesome. To obtain satisfactory amounts of product, the polymer-bound intermediates had to be protected at the 04 position so that cleavage could be accomplished with a mixture of trifluoroacetic acid/dichloromethane (1 9) (Scheme 7.44). 

Wadsworth-Emmons olefination with a variety of aldehydes to afford (E)-a,B-unsaturated and diene acyl tetramic and tetronic acids in good to excellent yields upon treatment with potassium tert-butoxide (2 equiv) in tetrahydrofuran. For readily enolizable substrates use of the N-protected systems is generally required. The following compounds have been prepared, in the indicated yields, in this manner ... 

Methyl-l,3-dioxolanyl Enol Acetate, 529 Pyrrolidinyl Enamine, 530 Benzyl Enol Ether, 530 Butyl Thioenol Ether, 530 Protection of Tetronic Acids, 530... 

The tetronic acid 181 is easily made by bromination of the ketoester 179 and treatment of 180 with KOH. Protection with the MOM group (MeOCH2-) gives 182 from which an extended enolate might be made. 

Tetronic Acids. - An attractive new route to tetronic acids (368) consists simply of a Blaise reaction between protected... 

The au rie2Si group is used to protect in the synthesis of morphine, methynoLide from D-glucose, C+)-Aplasmomycin, thromboxane B and lOa-homothrom-boxane A, prostaglandin t d in carbapenein synthesis.3u Ph,Si protects OH in the preparation of the optically pure TriF fragment of acyl tetronic acid... 

Tetronic acids (Scheme 18) are of great interest because their derivatives are widespread in nature. The Blaise reaction (addition of the zinc derivative of an a-bromo ester to a nitrile) has been applied to optically active 0-protected cyanohydrins. Isolation of the tetronic acids was achieved, in moderate yields, by acid hydrolysis and cyclization of the intermediate imines [94]. Better results were obtained in an optimized reaction sequence [141] (Scheme 18). 

A partial reduction of O-protected chiral cyanohydrins is also possible by reaction with Reformatsky reagents (Blaise reaction). The primarily formed imino intermediates can be hydrolyzed under very mild conditions to give the enamines ( )-15, which yield by treatment with strong acids the tetronic acids (R)-16 (Scheme 9) [39,40]. 

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