Ethyl 3-oxo-4-pentenoate

ETHYL 3-OXO-4-PENTENOATE (NAZAROVS REAGENT) (4-Pentenoic acid, 3-oxo-, ethyl ester)... 

Ethyl 3-oxo-4-pentenoate (Nazarov s reagent) is a well known annelating agent that has been used in several terpene and alkaloid8 syntheses. 

Other preparations of Nazarov s reagent and its analogs have been reported,7 but many of the procedures are labor-intensive and/or require special apparatus. The reported preparation of ethyl 3-oxo-4-pentenoate is facile (2 steps) and efficient (52% overall yield). Ail starting materials are commercially available, relatively inexpensive, and easily purified. The synthesis is also amenable to scale up and has been carried out successfully on a 1-mol scale. Other esters have also been synthesized by this method with overall yields ranging from 45-58% (see Scheme l).8 Finally, methacrolein and crotonaldehyde are also suitable reactants (see Scheme I). 

The final procedure in the volume documents a convenient synthesis of the classical annulating reagent ETHYL 3-OXO-4-PENTENOATE (NAZAROV S REAGENT). 

The conditions of Jones oxidation are compatible with complex organic compounds containing functional groups such as esters, ketones, amides and alkenes. For example, ethyl 3-hydroxy-4-pentenoate (7.3) on oxidation with Jones reagent gave ethyl 3-oxo-4-pentenoate (Nazarov s reagent) (7.4). 

Similar reactions can be employed for the preparation of quinolizines, usually from tetra-hydropyridines bearing a donor group on the C—N bond. Equation (30) summarizes two such syntheses, both employing ethyl 3-oxo-4-pentenoate (Nazarov s reagent) as the Michael acceptor... 

The catalyst was added to a mixture of (2R)-tert-b xiy 2- >SAR)- -[ R)- tert-butyldimethyl-silyloxy)ethyl]-2-oxo-4-(2-propenyl)- l-azetidinyl -4-pentenoate and (25)-tert-h xiy 2- (35,47 )-3-[(17 )-(f rf-butyldimethylsilyloxy)ethyl]-2-oxo-4-(2-propenyl)-l-azetidinyl -4-pentenoate in CH2CI2 (2 mL). The mixture was stirred for 12 h before destruction of the catalyst by exposure to air. The mixture was then evaporated, and the residue was chromatographed to afford a colorless oil as a mixture of the following-inseparable diastereoisomers (27 ,77 ,85)-f rf-butyl-l-aza-8-[(lR)-(f rf-butyldimethylsilyloxy)ethyl]-9-oxobicyclo[5.2.0]non-4-ene-2-carboxylate and 2S,1 R, S)-tert-hvXy l-aza-8-[(17 )-(f r -butyldimethyl-silyloxy)ethyl]-9-oxobicyclo[5.2.0]non-4-ene-2-carboxylate, in a yield of 97%, Rf = 0.41 (Et20 hexanes = 3 2). 

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