Intermolecular Aminocarbonylation of Alkenes using Concerted Cycloadditions of Iminoisocyanates

Abstract

The aminocarbonylation of alkenes is a powerful method for accessing the β-amino carbonyl motif that remains underdeveloped. Herein, the development of intermolecular aminocarbonylation reactivity of iminoisocyanates with alkenes is presented. This includes the discovery of a fluorenone-derived reagent, which was effective for many alkene classes and facilitated derivatization. Electron-rich substrates were most reactive, and this indicated that the LUMO of the iminoisocyanate is reacting with the HOMO of the alkene. Computational and experimental results support a concerted asynchronous [3 + 2] cycloaddition involving an iminoisocyanate, which was observed for the first time by FTIR under the reaction conditions. The products of this reaction are complex azomethine imines, which are precursors to valuable β-amino carbonyl compounds such as β-amino amides and esters, pyrazolones, and bicyclic pyrazolidinones. A kinetic resolution of the azomethine imines by enantioselective reduction (s = 13-43) allows access to enantioenriched products. Overall, this work provides a new tool to convert alkenes into β-amino carbonyl compounds.

Crystal Structure of the Chiral Azomethine Imine, (Z)-(S)-4-(tert-Butylcarbonylamino)-2-(2-methoxybenzylidene)-5-oxopyrazolidin-2-ium-1-ide, Obtained by the Cyclization of tert-Butyl (S)-2-[2-(methoxybenzylidene)hydrazine]-1-(hydroxymethyl)-2-oxocarbamate

“…The pyrazolyl ring has a betaine character with opposite charges on N1 and N2 atoms. The bond lengths and angles in the betaine ring are within the regions found for related compounds [4][5][6][18][19][20][21]. The C7-C12 bond length, 1.429(6) Å, is noticeably longer than the other C-C bond lengths, 1.377(6)-1.399(6) Å, in the phenyl ring, which indicates a degree of bond fixation arising.…”

“…In Table 3, selected data are provided for a number of 5-oxopyrazolidin-2-ium-1-ide derivatives, 12 of which contained an arylidene sbstituent [4,6,19,21,[25][26][27][28][29]. It is argued that the smaller this angle the greater possibilitythere will be for conjugation between the two fragments.…”

“…Various preparations of azomethine imide derivatives have been reported with more accessible routes involving reactions of pyrazolidin-3-ones with substituted benzaldehydes or using substituted acylhydrazines, RCONHNHR as precursors [4][5][6][7].…”

Aminimide Synthesis Using Concerted Amination Reactions of Alkenes: Scope and Mechanistic Information

“…Toward this end, we developed the thermal hydroamination of alkenes with hydrazide derivatives and discovered the propensity of related carbazate precursors to undergo a divergent aminocarbonylation reaction . In each case, concerted cyclizations (Cope-type for hydroamination , /[3 + 2] for aminocarbonylation) were proposed and supported by density functional theory (DFT) calculations. Despite these supporting data, corroborating experimental evidence was essential, both for the sake of fully understanding the mechanism and to guide potential future work on this system.…”

O‐Isocyanates as Uncharged 1,3‐Dipole Equivalents in [3+2] Cycloadditions

“…The first objective was to assess the feasibility of the intermolecular O ‐isocyanate cycloaddition. Analogous N ‐isocyanates have served as 1,3‐dipole equivalents in intermolecular [3+2] cycloadditions with π‐systems, notably forming stable azomethine imines, unlike the unisolable aza‐oxonium ylide [6i–l, 28] . Since reactivity through pathway A (Scheme 2) was validated in the corresponding intramolecular reaction, it was logical to target this pathway first in an intermolecular system.…”