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

Abstract

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...

Recent Advances in the Synthesis of Acylboranes and Their Widening Applicability

“…Lastly, two methods furnishing α-functionalized acyl MIDA-boronates should be described as these compounds have great synthetic value, especially in the synthesis of borylated heterocycles. 18 In 2017, the Yudin group reported a procedure to provide oxalyl boronates, which can also be viewed as α-keto functionalized acyl boronates ( Scheme 5 , entry 4). 18a Similar to the Perrin group above, they made use of the Upjohn dihydroxylation, but they used vinyl MIDA-boronates, so the reaction yielded boryl-substituted vicinal diols.…”

A Versatile Route to Acyl (MIDA)Boronates

“…Selective perborate cleavage of unsymmetrical gem‐diboronates 11 as described by Sharma is another route to alcohols 9 [14] . Finally, Wang disclosed that the reaction of chloroepoxides 12 (X=Cl) either with a Lewis acid or with various nucleophiles also furnishes acylborons 5 (path F ) [15] …”

One-Step Synthesis of Acylboron Compounds via Cu-Catalyzed Carbonylative Borylation of Alkyl Halides

“…More recently, Wang reported the nucleophilic ring opening of -chloroepoxyboronates to synthesize -functionalized acylborons. 12 Although these methods provide diverse approaches for synthesis of acylborons, they generally suffer from multi-step preparation of the precursors or limited substrate scope due to the use of stoichiometric reactive organometallic reagents and oxidants.…”