Oxidative Difunctionalization of Alkenyl MIDA Boronates: A Versatile Platform for Halogenated and Trifluoromethylated α‐Boryl Ketones

Lv, Wenxin; Zeng, Yao‐Fu; Li, Qingjiang; Chen, Yunyun; Tan, Dong‐Hang; Yang, Libin; Wang, Honggen

doi:10.1002/anie.201604898

Cited by 77 publications

(43 citation statements)

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“…Making use of similar vinyl MIDA boronate substrates, Wang has developed a new oxidative difunctionalization reaction. 146 After treating with SIBX along with either a fluorinating or trifluoromethylating reagent, the resulting α-boryl ketones can be converted to highly functionalized furans bearing MIDA boronates. A variety of other heterocycle-forming reactions have also been developed using MIDA boronate-containing substrates.…”

Section: Advances Towards a General Platform For Iterative Small Molementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

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Section: Advances Towards a General Platform For Iterative Small Molementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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“…[3a] The interaction between the p*orbital of the carbonyl group and the sC-B orbital [20] and/or the conjugation of the carbonyl with the aryl moiety in 12 b may provide at hermodynamic driving force for this process.T he scope of the reaction was not limited to aryl a-chloroepoxyboronates,a sa lkyl-substituted substrates were also applicable,a sr epresented by the effective bromination (14)and thiocyanation (15)reactions.It should be noted that the majority of these a-functionalized Boron-containing heteroarenes are of great value because of the versatility of the C À Bb ond in diverse chemical bond formations, [21] thereby facilitating the quick assembly of ah eteroaromatic-based molecular library. KSCN was also an effective nucleophile in providing 10.Inthis case,the evaporation of HFIP before the substitution reaction ensured ahigher yield.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…Interestingly, upon prolonging the reaction time, 12 a was cleanly isomerized intothe a-carbonyl boronate 12 b in good yield. Thea ir present in the reaction vessel might serve as the oxidant for aromatization for the synthesis of quinoxalines.Similarly,the telescoped synthesis of borylated imidazo[1,2-a]pyridines (18 a-g), borylated imidazo[1,2-b]pyridazine (19 a), borylated imidazo[1,2-a]pyrimidines( 19 b-e), were also feasible.I nterestingly,e xpanding the substitution/condensation methodology with phenylhydrazine resulted in af ormation of borylated 1,2-dihydro-1,2-diazete product (20). [1c, 22] The2 -boryl heteroarenes,h owever, are typically unstable, [23] and precludes their practical utilization.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…[3a] The interaction between the p*orbital of the carbonyl group and the sC-B orbital [20] and/or the conjugation of the carbonyl with the aryl moiety in 12 b may provide at hermodynamic driving force for this process.T he scope of the reaction was not limited to aryl a-chloroepoxyboronates,a sa lkyl-substituted substrates were also applicable,a sr epresented by the effective bromination (14)and thiocyanation (15)reactions.It should be noted that the majority of these a-functionalized Boron-containing heteroarenes are of great value because of the versatility of the C À Bb ond in diverse chemical bond formations, [21] thereby facilitating the quick assembly of ah eteroaromatic-based molecular library. [3,4,20] To the best of our knowledge,2 -boryl derivatives of imidazo[1,2-b]pyridazine (19 a)a nd 1,2-dihydro-1,2-diazete (20)have not been reported in the literature. Thee ngagements of ahaloketones as dielectrophiles in heterocycle synthesis encouraged us to examine the synthetic potential of achloroepoxyboronates in downstream transformations leading to borylated heterocycles,p articularly those among the privileged scaffolds in medicinal chemistry.…”

Section: Angewandte Chemiementioning

confidence: 99%

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Diversity‐Oriented Synthesis of α‐Functionalized Acylborons and Borylated Heteroarenes by Nucleophilic Ring Opening of α‐Chloroepoxyboronates

et al. 2019

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The ring-opening reactions of N-methyliminodiacetyl (MIDA) a-chloroepoxyboronates with different nucleophiles allowt he modular synthesis of ad iverse arrayo f organoboronates.T hese include seven types of a-functionalized acylboronates and seven types of borylated heteroarenes, some of which are difficult-to-access products using alternative methods.T he common synthons, a-chloroepoxyboronates, could be viably synthesized by at wo-step procedure from the corresponding alkenyl MIDAb oronates.M ild reaction conditions,g ood functional-group tolerance,a nd generally good efficiency were observed. The utility of the products was also demonstrated.There is growing interest in the chemistry of acylborons. [1] Their synthetic value,e xemplified by their involvement in chemoselective amide formation, [1b,d,2] as well as in the synthesis of borylated heterocycles [3] and a-aminoboronic acids, [4] have rendered them appealing targets in organic synthesis.T wo classic approaches toward acylboron preparation include the reaction of ab oryl metal species [5] with ac arbonyl electrophile,a nd the reaction of an acyl anion equivalent (generated under strong basic conditions) with an electrophilic boryl reagent. [2a, 6] An elegant alternative to these approaches is the Bode acylboron synthesis,wherein an electrophilic zwitterionic boronate reagent is used to react with organometallic reagents to afford potassium acyltrifluroborates (KATs). [2f, 7] Despite the great value,t he harsh reaction conditions associated with these methods eliminate their applicability in the preparation of more functionalized or complex acylboron. Very recently,B ode invented an ew trifluoroborate iminium reagent bearing at in moiety which could undergo Stille coupling with aryl-or vinylhalides to provide KATs. [8] By taking advantage of the stability of boronates with sp 3 -hybridized B, several conceptually new routes to acylborons based on the late-stage functional-group manipulation of ab oron-containing organic precursor were also developed (Scheme 1a). In this regard, the groups of Yudin and Ito reported the oxidation reaction of a-hydroxy boronates into acylboron compounds.T he key a-hydroxy boronate intermediates were prepared by Barton radical decarboxylation of MIDA a-borylcarboxylic acid, [3a] ringopening of 2-boryl oxirane, [3b] dihydroxylation of alkenyl boronates, [3c] oxidation of unsymmetrical geminal diborylalkanes, [9] and copper(I)-catalyzed borylation of aldehydes. [10] Remarkably,r ecent advances from the groups of Perrin, [11] Ito,and Bode [12] demonstrated the mild and concise synthesis of acylborons by means of chemoselective oxidative fragmentation of alkenyl N-methyliminodiacetyl (MIDA) boronates,e ither by dihydroxylation/meta-periodate cleavage or direct ozonolysis.Y et, the linear synthetic sequence involved may greatly compromise the overall efficiency as well as the diversity of the products.Herein, we report our realization of ad ivergent acylboron synthesis by an unexpected nucleophilic ring-opening/substitutio...

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“…[9] Thes p 3 -hybridized MIDAb oron center shows special stability,u nique reactivity,a nd was found to be indispensable in these transformations. [9] Thes p 3 -hybridized MIDAb oron center shows special stability,u nique reactivity,a nd was found to be indispensable in these transformations.…”

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gem‐Difluorination of Alkenyl N‐methyliminodiacetyl Boronates: Synthesis of α‐ and β‐Difluorinated Alkylborons

Lv,

Li,

et al. 2018

Angew Chem Int Ed

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Organofluorine compounds are widely used in pharmaceutical, agrochemical, and materials sciences.T he syntheses and applications of fluorinated organoborons facilitate the rapid and modular assemblies of fluorine-containing molecules because of the versatility of C À Bb onds in diverse chemical transformations.R eported herein is am igratory geminal difluorination of aryl-substituted alkenyl N-methyliminodiacetyl (MIDA) boronates using commercially available Py·HF as the fluorine source and hyperiodine as the oxidant. The protocol offers facile access to a-a nd bdifluorinated alkylboron compounds,b oth of which have previously been challenging to prepare.M ild reaction conditions,b road substrate scope,g ood functional-group tolerance,and moderate to good yields were observed. The utility of these products is demonstrated by further transformations of the CÀBbond into other valuable functional groups.

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Oxidative Difunctionalization of Alkenyl MIDA Boronates: A Versatile Platform for Halogenated and Trifluoromethylated α‐Boryl Ketones

Cited by 77 publications

References 64 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Diversity‐Oriented Synthesis of α‐Functionalized Acylborons and Borylated Heteroarenes by Nucleophilic Ring Opening of α‐Chloroepoxyboronates

gem‐Difluorination of Alkenyl N‐methyliminodiacetyl Boronates: Synthesis of α‐ and β‐Difluorinated Alkylborons

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