Divergent Chemo-, Regio-, and Diastereoselective Normal Electron-Demand Povarov-Type Reactions with α-Oxo-ketene Dienophiles

Abstract

The reactions between electron-rich 2-aza-dienes and α-oxo-ketenes derived from the Wolff rearrangement of 2-diazocycloalkane-1,3-diones chemo- and regioselectively produced spiro hydropyrid-4-ones with good to excellent diastereoselectivities. These reactions are likely to proceed via a domino Wolff/Friedel-Crafts/intramolecular Mannich process. Prolonged domino sequences also allowed the expeditious preparation of a series of pyrazolopyridine and pyridopyrimidine heterocycles.

Recent advances in ketene chemistry

“…Ketene 365 from thermolysis of diazo ketone 363 reacts with the iminopyrazole 364 by spiro-cyclization proposed to involve Friedel-Crafts type addition followed by hydrogen transfer and intramolecular cyclization leading to 366 (Scheme 128), as supported by computational studies. 175 The calculated transition state for the hydrogen transfer is shown in Figure 13. …”

An Efficient Synthesis of 6‐oxa‐spiro[3.4]octan‐1‐one Derivates Through 3‐diazochroman‐4‐one and Alkene

“…The reaction was presumably initiated by loss of nitrogen gas from 1 in the presence of Rh (II) forming benzofuran ketene intermediate through Wolff rearrangement, then captured by an alkene through [2+2] cycloaddition to give 6‐oxa‐spiro[3.4]octan‐1‐one . This cycloaddition proceeded with regio‐, stereo‐, and often chemoselectivity, as a result of the orbital‐controlled transformation in a concerted asynchronous mechanism . Configuration is dependent on the ketene substituents.…”

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

“…Over the past decade, asymmetric organic catalysis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], quite powerful for synthesizing various heterocyclic molecules, has formed the basis of several elegant approaches to construct chiral single-heterocycle piperidine skeletons with high efficiency and low toxicity under environmentally friendly conditions . In contrast, relatively few organocatalytic methods have been described to stereo-selectively form spirocyclic piperidine derivatives [30][31][32][33][34][35][36], particularly ones with a quaternary stereocenter [37][38][39].…”