Arylation of Diazoesters by a Transient NH Insertion Organocascade

Abstract

It takes two: A unique organocatalyzed cascade for the unsymmetric double arylation of α-nitrodiazoesters is described. This organocascade features the strategic use of carbene-activating anilines in conjunction with a urea catalyst, thus allowing for the synthesis of pharmaceutically attractive α-diarylesters through a transient NH insertion process.

Quantification of Electrophilic Activation by Hydrogen-Bonding Organocatalysts

“… 20 The internally activated BF 2 -urea 9 provided the largest shift within this class, in line with experimental reactivity data reported by Mattson and co-workers. 21 Finally, formally cationic species, including guanidinium, amidinium, and Takenaka’s azaindolium 14 ( 22 ) were the strongest binders, with wavelength shifts ranging from 26 to 34 nm (λ max = 473–465 nm). Interestingly, one of the strongest noncationic binders was thiophosphoramide 16 , possessing a pocket of three potential N–H donors.…”

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…Mattson and co-workers demonstrated this idea very nicely through the use of hydrogen bonds to activate the α-nitrodiazoester 130 in the presence of the urea catalyst 131 (Scheme 165). 460,461 The ability of ureas to recognize nitro groups through intermolecular hydrogen bond interactions forms the basis of a new catalytic process, termed hydrogen bond donor (HBD) activation, which exploits the urea nitro group recognition to facilitate the loss of nitrogen gas and thereby generates a reactive intermediate capable of N−H insertion. These authors made the initial observation that α-nitro-α-diazoesters such as 130 and aniline in the presence of 20 mol % 131 in toluene yielded the α-amino-α-arylester 132.…”

Stereodivergent Synthesis of N‐Heterocycles by Catalyst‐Controlled, Activity‐Directed Tandem Annulation of Diazo Compounds with Amino Alkynes

“…[3] Saµ and co-workers successively described novel cyclizations by trapping the vinyl ruthenium carbene intermediates generated in situ from alkyne and TMSCHN 2 . [6] Five-membered N-heterocycles,s uch as 2,3-dihydropyrroles,2 -methylene pyrrolidines,a nd 3-methylene pyrrolidines,are motifs found in numerous natural products,aswell as in biologically active pharmaceuticals.H owever,p repara-tion of such N-heterocyles generally requires diverse strategies from quite different starting materials. [5] Theh igh efficiency of this strategy and the ability to construct multiple bonds in one step has attracted considerable attention and resulted in the discovery of many novel transformations.…”