Catalytic Metal-free Allylic C–H Amination of Terpenoids

Abstract

The selective replacement of C–H bonds in complex molecules, especially natural products like terpenoids, is a highly efficient way to introduce new functionality and/or couple fragments. Here, we report the development of a new metal-free allylic amination of alkenes that allows the introduction of a wide range of nitrogen functionality at the allylic position of alkenes with unique regioselectivity and no allylic transposition. This reaction employs catalytic amounts of selenium in the form of phosphine selenides or selenoureas. Simple sulfonamides and sulfamates can be used directly in the reaction without the need to prepare isolated nitrenoid precursors. We demonstrate the utility of this transformation by aminating a large set of terpenoids in high yield and regioselectivity.

Enantioselective Catalytic C-H Amidations: An Highlight

“…In the presence of an achiral Co(III) catalyst, and a bulky chiral carboxylic acid derived from tert-Leucine, βamino thiocarbonyl derivatives bearing an α-quaternary center were obtained in high enantioselectivities (Scheme 6). Besides, intramolecular C(sp 3 )-H functionalizations, branch-selective allylic C-H amidation of terminal double bonds have been described [26][27][28][29]. Based on stoichiometric studies with TsNH 2 and the isolation of an allyl-Ir(III) complex, an inner sphere nitrenoid insertion of an η 3 -allyl irididium intermediate is advocated in these reactions (Scheme 5) [26].…”

“…Based on stoichiometric studies with TsNH 2 and the isolation of an allyl-Ir(III) complex, an inner sphere nitrenoid insertion of an η 3 -allyl irididium intermediate is advocated in these reactions (Scheme 5) [26]. Besides, intramolecular C(sp 3 )-H functionalizations, branch-selective allylic C-H amidation of terminal double bonds have been described [26][27][28][29]. Based on stoichiometric studies with TsNH2 and the isolation of an allyl-Ir(III) complex, an inner sphere nitrenoid insertion of an η 3 -allyl irididium intermediate is advocated in these reactions (Scheme 5) [26].…”

“…Undoubtedly, this work opens the door to future achievements on late-stage functionalization of other natural products. Besides, intramolecular C(sp 3 )-H functionalizations, branch-selective allylic C-H amidation of terminal double bonds have been described [26][27][28][29]. Based on stoichiometric studies with TsNH2 and the isolation of an allyl-Ir(III) complex, an inner sphere nitrenoid insertion of an η 3 -allyl irididium intermediate is advocated in these reactions (Scheme 5) [26].…”

Stereoretentive and regioselective selenium-catalyzed intermolecular propargylic C–H amination of alkynes

“…These protecting groups had also proved to be the highest yielding in the allylic amination, though we do not nd the same simple trend of increasing yield with more electron-poor sulfonamides as we did in our allylic amination. 42 We tested a variety of terminal and silyl alkynes (Scheme 3) under our optimized amination conditions. We found that alkynes bearing a wide range of functional groups, including ethers, esters, nitriles, protected alcohols and amines, and alkyl and aryl halides were aminated in high yields.…”

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

“… 2 These transformations can potentially be used as the basis of a terpene-based biorefinery, so the development of scalable processes to produce additional biorenewable products from bulk monoterpene feedstocks is highly desirable. 4 − 7 We have recently reported an optimal acid catalyzed ring opening process (6 M H 2 SO 4 , 90 °C, 2–4 h) to convert the major bicyclic monoterpene components (α-pinene, β-pinene, and 3-carene) present in the bulk monoterpene feedstocks CST, turpentine, and eucalyptus oil (cineole) into thermodynamic mixtures of p -menthadienes (α-terpinene, γ-terpinene, and isoterpinolene) ( p -MeDs) ( Figure 1 ). 8 Importantly, significant quantities of other biorenewable p -MeD feedstocks are also available as byproducts of acid catalyzed hydrolysis processes used to convert turpentine into α-terpineol and camphene, while ∼30 000 t of limonene (a p -MeD) is available as a waste product from fruit peel generated by the citrus industry.…”