Nazarov s reagent

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... 

Vinylcyclopentenones have undergone the Nazarov cyclization in good yield in the presence of Eaton s reagent (eq 4). However, other reagents may be more generally useful, since there are reports of Eaton s reagent not providing optimal results in this... 

Cyclopentenone annelation (cf. 10,444). The reagent undergoes a Nazarov-type cyclization with an a,/S-unsaturated acid chloride to give an annelated 3-phenylthio-cyclopentenone. This reaction was used to prepare the bicyclic cyclopentenone 3, a useful intermediate in synthesis of cyclopentenoid natural products, such as hirsutene (4).3... 

In a similar context, y,5-unsaturated p-ketoesters (Nazarov reagents) have also been employed as suitable functionalized Michael donor substrates for a Michael/Michael cascade reaction with nitroalkenes using, in this case, Takemoto s catalyst 68a (Scheme 7.65). This reaction proceeded in a tandem... 

A similar reaction was also reported by Jprgensen s group regarding the addition of Nazarov reagents (75) to enals (15). The reaction furnishes highly substituted cyclohexanones in high yields and stereoselectivities via an organocatalytic tandem Michael/Morita-Baylis-Hillman reaction catalyzed by the diphenylprolinol derivative VII [50]. 

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