Intrinsic Gas-Phase Electrophilic Reactivity of Cyclic N-Alkyl- and N-Acyliminium Ions

Abstract

The intrinsic gas-phase reactivity of cyclic N-alkyl- and N-acyliminium ions toward addition of allyltrimethylsilane (ATMS) has been compared using MS(2) and MS(3) pentaquadrupole mass spectrometric experiments. An order of electrophilic reactivity has been derived and found to agree with orders of overall reactivity in solution. The prototype five-membered ring N-alkyliminium ion 1a and its N-CH(3) analogue 1b, as well as their six-membered ring analogues 1c and 1d, lack N-acyl activation and they are, accordingly, inert toward ATMS addition. The five- and six-membered ring N-acyliminium ions with N-COCH(3) exocycclic groups, 3a and 3b, respectively, are also not very reactive. The N-acyliminium ions 2a and 2c, with s-trans locked endocyclic N-carbonyl groups, are the most reactive followed closely by 3c and 3d with exocyclic (and unlocked) N-CO(2)CH(3) groups. The five-membered ring N-acyliminium ions are more reactive than their six-membered ring analogues, that is: 2a > 2c and 3c > 3d. In contrast with the high reactivity of 2a, its N-CH(3) analogue 2b is inert toward ATMS addition. For the first time, the transient intermediates of a Mannich-type condensation reaction were isolated-the beta-silyl cations formed by ATMS addition to N-acyliminium ions-and their intrinsic gas-phase behavior toward dissociation and reaction with a nucleophile investigated. When collisionally activated, the beta-silyl cations dissociate preferentially by Grob fragmentation, that is, by retro-addition. With pyridine, they react competitively and to variable extents by proton transfer and by trimethylsilylium ion abstraction-the final and key step postulated for alpha-amidoalkylation. Becke3LYP/6-311G(d,p) reaction energetics, charge densities on the electrophilic C-2 site, and AM1 LUMO energies have been used to rationalize the order of intrinsic gas-phase electrophilic reactivity of cyclic iminium and N-acyliminium ions.

Biomimetic oxidation of praziquantel catalysed by metalloporphyrins

“…4. The parent ion (PI) of PZQ, at m/z 313, is formed by protonation of one of the amide groups [31]. The PZQ MS 2 spectrum, Fig.…”

One‐Step Synthesis of the 1‐Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf)2‐Catalyzed Cycloisomerization

“…In the similar N ‐acyliminium ion spirocyclization, Kibayashi et al. have suggested that the spirocyclization preferentially occurs via the intermediacy of five‐membered ring N ‐acyliminium ions rather than via the six‐membered ring analogue such as II , [11] because the LUMO energy of five‐membered ring N ‐acyliminium ions with exocyclic amide carbonyl groups is lower than that of six‐membered ring analogues [12] . Thus, the less electrophilic reactivity of the six‐membered ring N ‐acyliminium ion II would inhibit the cyclization to 7 d .…”

“…In the similar N-acyliminium ion spirocyclization, Kibayashi et al have suggested that the spirocyclization preferentially occurs via the intermediacy of five-membered ring Nacyliminium ions rather than via the six-membered ring analogue such as II, [11] because the LUMO energy of fivemembered ring N-acyliminium ions with exocyclic amide carbonyl groups is lower than that of six-membered ring analogues. [12] Thus, the less electrophilic reactivity of the sixmembered ring N-acyliminium ion II would inhibit the cyclization to 7 d. Therefore, exogeneous H 2 O contaminant reacts with the iminium ion moiety in II, yielding the diketone intermediate III which would be led to the unwanted diketone 8 d and α,βunsaturated ketone 9 d (path b). The factors of the unsuccessful cycloisomerization to 7 d could be related to steric bulkiness of an N-Boc group as well as the aforementioned less electrophilic reactivity of six-membered ring N-acyliminium ion II.…”

Katalytische asymmetrische Additionen von Enolsilanen an in situ erzeugte zyklische, aliphatischeN‐Acyliminiumionen

“…Wir stellten die Hypothese auf, dass die Schwierigkeit, diese hochreaktiven Iminiumionen zu bändigen, in (1) ihrer extremen Elektrophilie und (2) der Existenz von zwei sich schnell umwandelnden s-cis/strans-Konformern liegen könnte. [20,21] Angesichts der Fähigkeit von sehr starken und umzäunten IDPi-Katalysatoren, Reaktionen mit flexiblen, energiereichen Kationen zu kontrollieren, folgerten wir, dass solche Organokatalysatoren auch eine Lösung für diese seit langem bestehende Herausforderung bieten könnten. Hier berichten wir über eine hoch enantioselektive Silylium-IDPi-katalysierte Mukaiyama-Mannich-Reaktion, bei der Enolsilane mit in situ erzeugten N-(exo-Acyl)iminiumionen reagieren, um verschiedene nützliche α-substituierte Stickstoff-Heterozyklen zu liefern, darunter Zwischenprodukte für verschiedene Naturstoffe (Abbildung 1).…”