Autocatalytic Domino Michael Reaction Leading to Bicyclo[2.2.2]octane-2,5-dione Derivatives

Abstract

In the presence of a catalytic amount of lithium amide, the reaction of oxophorone with electron-deficient olefins afforded bicyclo[2.2.2]octane-2,5-dione derivatives in high yields. The reaction proceeds autocatalytically by an enolate of bicyclo[2.2.2]octane-2,5-dione, generated by an initial domino Michael reaction.

Anionic Diels–Alder Chemistry of Cyclic Sodium Dien-1-olates Delivering Highly Stereoselective and Functionalized Polycyclic Adducts

“…In sharp contrast, when a strong base DBU was used, a high selectivity for product 10 over 9 was observed, particularly in a more polar solvent DMF (entry 19 vs 20). According to Table , not only was the trans isomerism of dienophile 8 constantly preserved in products, but also no Michael-addition intermediates were detected in all cases examined . To elucidate these outcomes, a plausible mechanism is proposed as follows.…”

Recent Advance of Domino Michael Reaction in Natural Product Synthesis

“…Example of the domino Michael reaction using a catalytic amount of base is rare. 58 Recent developments in the area of organocatalysts has changed the game in the domino Michael reaction. The use of organocatalysts has widely expanded the degree of freedom in the design of reaction and the substrate scope and has greatly advanced the domino Michael reaction, in which a variety of frameworks have been constructed [11][12][13][14][15][16]59 under mild reaction conditions employing a variety of organocatalysts.…”

“…Clinprost (58) in Figure 6 is a stable analogue of prostacyclin (PGI 2 ) and exhibits a potent neuroprotective activity in animal studies. According to the same [3 + 2] domino Michael strategy as in the Figure 5, Umekubo and Hayashi demonstrated a total synthesis of clinprost (58) (Figure 7).…”

Original Mitsunobu-Triggered Sequence Involved in a One-Pot Domino Process toward Tetracyclic Systems Bearing a Bis-N,O-acetal Junction

“…The late 20th and early 21st centuries have witnessed an unprecedented increase of powerful tools such as domino sequences , and multicomponent , reactions to access architecturally complex molecular frameworks. This modern conception of organic chemistry is quickly replacing traditional stepwise approaches to meet environmental and economic demands, in particular for the high-throughput screening of novel scaffolds of biological interest.…”