Oxidative Amidation of Phenols through the Use of Hypervalent Iodine Reagents: Development and Applications

Abstract

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain.

General One‐Pot Reductive gem‐Bis‐Alkylation of Tertiary Lactams/Amides: Rapid Construction of 1‐Azaspirocycles and Formal Total Synthesis of (±)‐Cephalotaxine

“…The fact here, however, seemed to preclude the role of DTBMP as a nucleophile to first react with triflic anhydride. Indeed, it has been reported that due to its steric hindrance, DTBMP does not react with triflic anhydride to generate the reactive pyridinium intermediate G. [22a] Thus, although the exact role of DTBMP is not yet clear at this stage, a new plausible mechanism for the Tf 2 Oactivated addition of organometallic reagents to lactams and [3][4][5][6][7][8]. Mention should be made that to ensure complete lactam activation, the activation time may be prolonged to 2 h, or the reaction temperature may rise from À78 to 0 8C before cooling back to À78 8C for Grignard reagent addition.…”

“…Representative bioactive alkaloids containing 1-aza-A C H T U N G T R E N N U N G spirocycles are shown in Figure 1. [4] Although much effort has been made to construct such structural motif, [5,6] the transformation of lactams and amides into the corresponding tert-alkylamines by one-pot reductive bis-alkylation with different organometallic reagents (Scheme 1) is both a highly desirable and a challenging objective. [6] The merit of this transformation is also linked to the high stability of lactams/amides, the powerful directing ability of lactams/ amides for metallation [7] and C À H activation, [8] as well as the ready availability of both lactams/amides [9] and Grignard/organolithium reagents.…”

“…[14] The second tactic is based on activation of amide by conversion to N-carbamoyl lactam derivatives, followed by stepwise transformations such as organometallic reagents addition and a-amidoalkylation of the resulting N-acyliminium ion precursors. [4,6] The third one, developed by Murai [15] and Renaud, [16] consists of transforming amides/lactams into thioamide or selenoamide derivatives, followed by in situ activation by using S-methylation and the addition of organometallic reagents. On the basis of the latter work, Renaud and co-workers have thus established a flexible approach to 1-azaspirocycles.…”

Crystal structure of 2,3,6a,9-tetrahydro-1H-6,9-methanopyrrolo [2,1-i][2,1]benzisothiazol-10(6H)-one 5,5-dioxide, C11H13NO3S

“…The title compound is an intermediate in an ongoing synthetic study on Himandrine and related alkaloids [1,2]. The lattice contains two crystallographically independent molecules in the asymmetric unit, however there are no significant geometric differences between the two molecules.…”

Biomimetic Synthesis of Alkaloids Derived from Tyrosine: The Case of FR‐901483 and TAN‐1251 Compounds

“…This precise transformation was unknown until the late-1990s, and, indeed, it was believed not to be feasible. This lore was rooted in an important Technology for oxidative amidation of phenols finally emerged in 1998 thanks to research carried out in our own laboratories [19]. First of all, we perceived a mechanistic analogy between the formation of lactone 67 upon oxidative activation of the phenol and the results obtained by Knapp during a study of the iodoamidation of olefins [20].…”