Iterative direct C<sub>(sp3)</sub>–H functionalization of amines: diastereoselective divergent syntheses of α,α′-disubstituted alicyclic amines

Mahato, Sujit; Jana, Chandan K.

doi:10.1039/c6ob02257j

Cited by 16 publications

(27 citation statements)

References 65 publications

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“…In the above reaction, a byproduct was isolated and identified as the multisubstituted phenol 3, the O-deacetyl product of 2, through characterization by 1 H NMR, 13 C NMR, and HMRS. This observation prompted us to explore a diverse synthesis of multisubstituted phenols 3 17 directly starting from the same starting material 1.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

Wan

Zhang

et al. 2018

J. Org. Chem.

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Novel acylamino-directed relay disubstitutions realize the sequential difunctionalizations of anilides (1) under mild and metal-free conditions for the first time. This [bis(trifluoroacetoxy)iodo]benzene (PIFA) and BF3·Et2O promoted straightforward reaction produces a series of p-acetoxyl- or p-alkoxyl-o-nitro-N-arylamides (2), which are key scaffolds of various drugs, functional materials, and bioactive molecules. The flexibility with respect to the functional groups in these products affords this novel protocol excellent versatility for synthetic applications.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…Ethyl acetate is abbreviated as EA. 1 H NMR and 13 C{ 1 H} NMR spectra were recorded on a Bruker Avance/600 ( 1 H, 600 MHz; 13 HRMS (>95%) was confirmed by 1 H NMR and 13 C{ 1 H} NMR spectroscopic analysis. Melting points were measured on a melting point apparatus equipped with a thermometer and were uncorrected.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

Wan

Zhang

et al. 2018

J. Org. Chem.

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“…The iterative C(sp 3 )–H activation of cyclic amines to afford the N,O‐acetals by Ag 2 O following alkyl Grignard addition has been applied in the synthesis of α,α′‐disubstituted cyclic amines . We envisioned that the opening of aminal 2c/3c by an alkyl Grignard following the second activation/Grignard addition can provide the 2,5‐disubstituted pyrrolidine intermediate needed for the synthesis of 3,5‐disubstituted indolizidine 223AB .…”

Section: Methodsmentioning

confidence: 99%

C‐H Functionalization of Amino Alcohols by Osmium Tetroxide/NMO or TPAP/NMO: Protecting Group‐Free Synthesis of Indolizidines (–)‐223AB and 3‐epi‐(–)‐223AB

Chen

Wang

2019

Eur J Org Chem

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The oxidative cyclization of amino alcohols by osmium tetroxide/NMO or tetrapropylammonium perruthenate (TPAP)/NMO was found to provide an N,O-acetal moietyThe functionalization of a carbon adjacent to a tertiary amine nitrogen via a C(sp 3 )-H activation has been developed over the past decade, and such methods include oxidative cross-dehydrogenative coupling (CDC) reactions, [1,2] electro-oxidative activations and photoredox reactions. [3,4] In these processes, the generated iminium cations are important intermediates for the subsequent C-C, C-O, and C-N bond formations. In particular, the formation of a C-O bond by the addition of an oxygen nucleophile to the iminium cation gives an N,O-acetal moiety. Such manipulation can simultaneously activate and protect a specific carbon, thus providing greater efficiency and flexibility for subsequent synthetic transformations. Since the N,O-acetal moiety can be assembled or cleaved whenever carbon activation or subsequent functionalization is needed, tedious protection/deprotection steps in the synthetic sequence can be avoided.Unfortunately, existing N,O-acetal generation strategies involving the trapping of oxygen by the iminium cation are better suited to the addition of phenolic oxygens via Cu(OAc) 2 , Ag 2 O or I 2 /H 2 O 2 mediated oxidations (Scheme 1a), [5][6][7] or reactions of aryl aldehydes/aryl alkyl ketones with amines under metal and oxidant free conditions (Scheme 1b). [8] The limited examples involving nonphenolic hydroxyl groups include the electrooxidative cyclization or Ir(ppy) 2 (dtb-bpy)PF 6 catalyzed photooxidation of hydroquinoyl and hydroisoquinoyl alcohols (Scheme 1c), [4b,4c] and FeCl 3 [9] or CHDFe(CO) 3[10] mediated oxidations of saturated amino alcohols (Scheme 1d). Herein, we disclosed two novel and general procedures for the oxidative cyclization of saturated amino alcohols. When amino alcohols 1a and 1b were used as test substrates, we were surprised to find that a catalytic amount of OsO 4 with NMO or a catalytic amount of tetrapropylammonium perruthenate (TPAP) with NMO are ef- [a]

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“…Amines with α-substitution are doubtlessly crucial components in pharmaceuticals and natural products. [32,33] As such, there is a broad interest in developing these motifs using direct functionalization of CÀ H bonds present next to the nitrogen atom. Recently, transition metal-free strategies such as Nlithiation mediated imine formation of cyclic amines followed by reaction with organometallic nucleophiles [34] and quinone mediated ketimine formation from primary amines followed by in situ oxidation [35] have emerged for α-functionalization of amines among others.…”

Section: α-Cà H Activation and Functionalization Of Aminesmentioning

confidence: 99%

“…Amines with α‐substitution are doubtlessly crucial components in pharmaceuticals and natural products [32,33] . As such, there is a broad interest in developing these motifs using direct functionalization of C−H bonds present next to the nitrogen atom.…”

Section: α‐C−h Activation and Functionalization Of Aminesmentioning

confidence: 99%

Site‐Selective C(sp³)−H and C(sp²)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

et al. 2020

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Amines represent an important class of industrial feedstock as many pharmaceuticals, agrochemicals, petrochemicals, and healthcare products are derived from them. Researchers are developing methodologies for the functionalization of aliphatic and aromatic amines by improving their functionalgroup tolerance, regioselectivity, chemoselectivity, and time efficiency. Among the most studied methods for the derivatization of amines, CÀ H activation is gaining significant interest due to easy-to-follow, environmentally friendly, and time-economic protocols. Transition-metal-catalyzed C(sp 3)À H and C (sp 2)À H activation is a fascinating field of chemistry where the electronics of the structure, functional group characteristics, and nature of the directing group (DG) decide the outcome of the chemical reaction. Under carefully tailored reaction conditions and by a selection of the correct substrates/reagent, site-specific CÀ H functionalization can be achieved at different positions with respect to the amine group. This review provides an overview of the combination of carbon-carbon and carbon-heteroatom functionalizations and describes recent state-of-the-art methodologies, as well as challenges in this emerging field. 1. Introduction 2. α-CÀ H Activation and Functionalization of Amines 3. β-CÀ H Activation and Functionalization of Amines 4. γ-CÀ H Activation and Functionalization of Amines 5. δ-CÀ H Activation and Functionalization of Amines 6. Concluding Remarks

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Iterative direct C_(sp3)–H functionalization of amines: diastereoselective divergent syntheses of α,α′-disubstituted alicyclic amines

Cited by 16 publications

References 65 publications

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

C‐H Functionalization of Amino Alcohols by Osmium Tetroxide/NMO or TPAP/NMO: Protecting Group‐Free Synthesis of Indolizidines (–)‐223AB and 3‐epi‐(–)‐223AB

Site‐Selective C(sp³)−H and C(sp²)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

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Iterative direct C(sp3)–H functionalization of amines: diastereoselective divergent syntheses of α,α′-disubstituted alicyclic amines

Cited by 16 publications

References 65 publications

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation

C‐H Functionalization of Amino Alcohols by Osmium Tetroxide/NMO or TPAP/NMO: Protecting Group‐Free Synthesis of Indolizidines (–)‐223AB and 3‐epi‐(–)‐223AB

Site‐Selective C(sp3)−H and C(sp2)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

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Iterative direct C_(sp3)–H functionalization of amines: diastereoselective divergent syntheses of α,α′-disubstituted alicyclic amines

Site‐Selective C(sp³)−H and C(sp²)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy