Directed Remote Lateral Metalation: Highly Substituted 2‐Naphthols and BINOLs by In Situ Generation of a Directing Group

Patel, Jignesh J.; Laars, Marju; Gan, Wei; Board, Johnathan; Kitching, Matthew O.; Snieckus, Victor

doi:10.1002/anie.201805203

Cited by 13 publications

(6 citation statements)

References 39 publications

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“…[17] Without purification, the mixture was further deprotected through hydrogenolysis under catalysis with Pd/ C to accomplish the desired target, in racemic form, in 65 % yield over 2 steps. The 1 H NMR, 13 C NMR, and mass spectral data obtained for the synthetic (AE)-ABX, whose structure is further unambiguously confirmed by an X-ray crystallographic analysis, [18] are in good agreement with those reported for the naturally occurring product. [11c,d, 19] Vinylogous [4+2] anionic annulation can also be applied to other 1,2-dipolar synthons such as the cyano or imine group to rapidly incorporate a pyridine-2-ol or pyridine-2-one unit in various alkaloid systems, historically, many of which might potentially possess a wide range of biological activities.…”

Section: Angewandte Chemiesupporting

confidence: 70%

Development of a Cross‐Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)‐ABX

Huang

Shia

2020

Angew Chem Int Ed

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The cross‐conjugated vinylogous [4+2] anionic annulation has been newly developed, the cascade process of which has a high preference for regiochemical control and chemoselectivity, giving rise to exclusively Michael‐type adducts in moderate to high yields (up to 94 %, 35 examples). By making use of this approach as a key operation, the first total synthesis of natural antibiotic ABX, in racemic form, has been successfully achieved in a concise 7‐step sequence with an overall yield of about 20 %.

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Section: Angewandte Chemiesupporting

confidence: 70%

Development of a Cross‐Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)‐ABX

Huang

Shia

2020

Angew Chem Int Ed

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“…Such a migration sequence circumvents the removal and introduction of the DMG and would allow the same group to direct functionalization at a new, remote location. In continuing efforts to invent new D o M‐based chemistry, we now report the successful attainment of the DMG dance concept ( 3 → 4 ), which establishes a regioselective route to 7‐azaindoles bearing diverse C2 (see Table ) and C2 and C6 (see Figure ) substitution patterns.…”

Section: Figurementioning

confidence: 89%

Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

et al. 2019

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The regioselective functionalization of 7‐azaindole by controlled annular isomerism employing a directed metalation‐group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenching with an electrophile to furnish C6‐substituted derivatives which, in the presence of a catalytic amount of ClCONR2 promotes a carbamoyl group shift or dance from N7 to N1. A second directed metalation/electrophile quench sequence leads to 2,6‐substituted azaindoles. Optimization of the metalation conditions for C2 and C6, separately and iteratively, is presented. Using the directed metalation group dance strategy, a late‐stage deuteration of an antipsychotic drug is described. Overall, the controlled migration of the carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.

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“…Such amigration sequence circumvents the removal and introduction of the DMG and would allow the same group to direct functionalization at an ew,r emote location. In continuing efforts to invent new DoM-based chemistry, [10] we now report the successful attainment of the DMG dance concept (3!4), which establishes ar egioselective route to 7-azaindoles bearing diverse C2 (see Table 1) and C2 and C6 (see Figure 3) substitution patterns.…”

mentioning

confidence: 85%

Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

et al. 2019

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The regioselective functionalization of 7-azaindole by controlled annular isomerism employing ad irected metalation-group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenchingwith an electrophile to furnish C6-substituted derivatives which, in the presence of ac atalytic amount of ClCONR 2 promotes ac arbamoyl group shift or dance from N7 to N1. As econd directed metalation/electrophile quench sequence leads to 2,6substituted azaindoles.O ptimization of the metalation conditions for C2 and C6, separately and iteratively,i sp resented. Using the directed metalation group dance strategy,alate-stage deuteration of an antipsychotic drug is described. Overall, the controlled migration of the carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.Azaindoles occupy ap rominent position in drug discovery research because of their diverse bioactivities,e specially in protein kinase inhibition for the development of anticancer therapies.Among the four isosteres,the 7-azaindole scaffold, also present in arare class of natural products, [1] has emerged as the key heterocycle for structural modification towards new bioactive molecules ( Figure 1A). [2] Among the synthetic routes for 7-azaindoles,metalation-based methodologies have achieved dominance over classical processes because of the advantages of regioselectivity,m ultiple substitution, and ready modification of the prototype nucleus. [3,4] In previous efforts,w ed emonstrated the power of the directed ortho metalation (DoM) reaction in new halogen-dance strategies, [5] anionic ortho-Fries rearrangement processes, [6] latent directed metalation group (DMG) protocols, [7] and, as demonstrated on the 7-azaindole framework, walk-around-the-ringsequences. [4a,b,8] Whilst synthetically powerful, these metalationbased approaches involve several steps:D MG introduction, its use to direct the functionalization event, and its subsequent removal or modification.

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Directed Remote Lateral Metalation: Highly Substituted 2‐Naphthols and BINOLs by In Situ Generation of a Directing Group

Cited by 13 publications

References 39 publications

Development of a Cross‐Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)‐ABX

Development of a Cross‐Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)‐ABX

Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

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