A Simple and Broadly Applicable C−N Bond Forming Dearomatization Protocol Enabled by Bifunctional Amino Reagents

Abstract

A C−N bond forming dearomatization protocol with broad scope is outlined. Specifically, bifunctional amino reagents are used for sequential nucleophilic and electrophilic C−N bond formations, with the latter effecting the key dearomatization step. Using this approach, γ‐arylated alcohols are converted to a wide range of differentially protected spirocyclic pyrrolidines in just two or three steps.

Dearomatizing Amination Reactions

“…[38,39] More recently, Bower and co-workers have reported a base mediated method that exploits direct displacement of the NÀ O bond of activated hydroxylamine based systems 57. [40] For processes involving indoles, smooth dearomatization occurred under very simple conditions to provide spirocyclic pyrrolidines such as 58 a-e (Scheme 17A). Here, the O-based leaving group is either tosylate or pentafluorobenzoate, and a variety of carbamate and sulfonamide N-protecting groups are tolerated.…”

Advances in the Synthesis of Benzo‐Fused Spiro Nitrogen Heterocycles: New Approaches and Modification of Old Strategies

“…In the case of R 4 , R 5 or R 6 substituted homologs 191, diastereomeric pairs of spiro cycles 192 are formed, the ratio of which ranges from 2 : 1 to 20 : 1 (Scheme 50). [234] The halogen atom transfer radical cyclization has been evaluated on N-(indolylmethyl)trichloroacetamides 193 under Cu(I)Cl catalysis using nitrogen containing ligands, such as tetramethylethylene diamine, pentamethyldiethylene triamine or bipyridine. The ring closure leads to the formation of 3,3-spiro-3Hindoles 194 in moderate to good yields by a 5-exomechanism.…”

Rapid Oxidation Indoles into 2‐Oxindoles Mediated by PIFA in Combination with n‐Bu4NCl ⋅ H2O

“…Treating hypervalent iodine compounds, such as PhI(OAc) 2 (PIDA), with halides is well-known to generate diacetoxyiodate(I) anions or acetyl hypoiodites that can react with double bonds or activated methylene groups to deliver a range of unusual CÀ C, CÀ O, or CÀ N bond-forming reactions (Figure 2B). [9,10] Considering the above-mentioned limitations for the construction of 3-substituted 2-oxindoles and our continued interest in the development of mild conditions for the functionalization of heterocyclic compounds, [11] we believed that an alternative protocol that rapidly transforms indoles into 2-oxindoles under mild conditions with broad functional group tolerance represents a practical advantage. In particular, we wished to pursue an efficient way of generating HOX in situ, which would chlorohydroxylate the indole and then rapidly eliminate HX to generate the 2-oxindole product.…”