1,2‐Oxazine N‐Oxides as Catalyst Resting States in Michael Additions of Aldehydes to Nitro Olefins Organocatalyzed by α,α‐Diphenylprolinol Trimethylsilyl Ether

Abstract

By combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D6)benzene, 4‐Å molecular sieves, room temperature) intermediates of the corresponding catalytic Michael‐addition cycles were formed and characterized (IR, NMR, X‐ray analysis; Schemes 3–6 and Fig. 1–3). Besides cyclobutanes 2, 1,2‐oxazine N‐oxide derivatives 3–6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3–5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2).

Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions Generating All‐Carbon Quaternary Stereogenic Centers

“…For example, N-tosylated pyrrolidine 4 was obtained by reductive amination of gnitroaldehyde 3 a followed by tosylation (Scheme 2a). [15,20] Thus, for the herein presented peptidic catalyst H-d-Pro-Pro-NHCH(Ph)CH 2 -4-Me-C 6 H 4 (1 g) the presence of an additional acid was expected to be important. Reduction of the aldehyde moiety within g-nitroaldehyde 3 c using NaBH 4 yielded after intramolecular cyclisation of the initially formed hydroxyester the crystalline g-butyrolactone 5 in 95 % yield (Scheme 2 b).…”

Mechanism of Diphenylprolinol Silyl Ether Catalyzed Michael Addition Revisited—but Still Controversial

“…[8] This compound has previously also been shown to be an intermediate in stoichiometric processes. In addition to the cyclobutane 2 a minor product, which equilibrates with 2 and which proved to be the 1,2-oxazine N-oxide 6 resulting from a formal [2+4] addition of the enamine and nitro olefin, was identified (Scheme 3).…”

“…In addition to the cyclobutane 2 a minor product, which equilibrates with 2 and which proved to be the 1,2-oxazine N-oxide 6 resulting from a formal [2+4] addition of the enamine and nitro olefin, was identified (Scheme 3). [8] This compound has previously also been shown to be an intermediate in stoichiometric processes. [5] The zwitterionic intermediate 3, which is excluded from Blackmonds modified catalytic cycle, plays according to Seebach a crucial role in the reaction as it may lead to dissociation to enamine and nitro olefin, to cyclobutane 2 and oxazine 6, as well as to product.…”

“…In the initial part of the reaction, the cyclobutane derivative 2 (Scheme 2) is rapidly formed, as evidenced by reaction calorimetry reported by Blackmond and co-workers, [7] as well as by in situ NMR spectroscopy by Seebach, Hayashi and co-workers, [6] and later also by X-ray crystallographic studies. [8] The cyclobutane is obtained as a single isomer by reversible formal [2+2] cycloaddition of the enamine and the nitro olefin, most likely occurring via the zwitterionic intermediate 3, [9] which results from reversible addition of the enamine to the nitro olefin. The cyclobutane was found to serve as the off-cycle resting state of the catalyst.…”

Die Diarylprolinolsilylether: zehn Jahre später

“…Diese Reaktion wurde von den Arbeitsgruppen von Blackmond, Seebach, Hayashi, Pµpai und Pihko auf verschiedene Weise,u nter anderem durch NMR-Spektroskopie,R eaktionskalorimetrie,R eaktionskinetik und rechnerische Methoden, untersucht. [23] Diesen Untersuchungen zufolge entstehen während der Reaktion mehrere klar getrennte Zwischenstufen, darunter ein Cyclobutan und ein 1,2-Oxazin-N-oxid, die sich vermutlich auf die Selektivität und das kinetische Profil der Reaktion auswirken. Diese Arbeiten machen deutlich, dass die grundlegenden Prinzipien der Aminokatalyse zwar auf einfachen Konzepten beruhen, die wirkenden Mechanismen aber kompliziert sein kçnnen und dass die Vorstellung,a minokatalytische Umwandlungen seien mechanistisch einfach, trügen kann.…”