Carbopalladation of C–C σ-bonds enabled by strained boronate complexes

Abstract

Transition metal-catalysed cross-coupling reactions, particularly those mediated by palladium, are some of the most broadly used chemical transformations. The fundamental reaction steps of such crosscouplings typically include oxidative addition, transmetalation, carbopalladation of a -bond, and/or reductive elimination. Herein, we describe an unprecedented fundamental reaction step: a C−C σ-bond carbopalladation. Specifically, an aryl palladium(II) complex interacts with a −bond of a strained bicyclo[1.1.0]butyl boronate complex to enable addition of the aryl palladium(II) species and an organoboronic ester substituent across a C−C -bond. The overall process couples readily available aryl triflates and organoboronic esters across a cyclobutane unit with total diastereocontrol. The pharmaceutically-relevant 1,1,3-trisubstituted cyclobutane products are decorated with an array of modular building blocks, including a boronic ester which can be readily derivatized.

High‐Throughput Ligand Screening Enables the Enantioselective Conjugate Borylation of Cyclobutenones to Access Synthetically Versatile Tertiary Cyclobutylboronates

“…[9,10] To develop ag eneral, complementary approach to access cyclobutylboronates,w e envisioned using ac opper-catalyzed conjugate borylation of cyclobutenones.P ioneering work by Hosomi [11] has shown that conjugate borylation provides an extremely efficient entry into optically enriched cyclopentyl-and cyclohexylboronates, [12,13] however the cyclobutane equivalent is lacking in the literature.T oaddress this void, we targeted the conjugate borylation of a,b-disubstituted cyclobutenones (Figure 2c), which would provide the first examples of enantioenriched tertiary cyclobutylboronates. [14] Furthermore,i tw ould also allow access to polysubstituted cyclobutanones,f or which catalytic enantioselective approaches remain scarce. [15] The expected keto-boronate products can undergo bidirectional functionalizations,making them valuable medicinal chemistry intermediates.…”

“…Protodeboronation resulted in the formal anti cyclobutenone hydrogenation product 8 in moderate yield and 10:1 dr. Thep otassium trifluoroborate salt 9 was obtained in ah igh 94 %y ield and was found to be as uitable substrate for ar hodium-catalyzed aldehyde addition to obtain diketone 10 as amixture of diastereomers upon oxidation. [27] Alternatively,t he corresponding ketal 11 can serve as av iable substrate for an umber of carbon-carbon bond forming processes.Z weifel olefination, alkynylation, and acetylation were possible in good to high yields (12)(13)(14), using previously established stereoselective lithiation-1,2boryl migration chemistry,which has been largely developed by Aggarwal and co-workers. [28] In summary,acatalytic enantioselective approach to novel tertiary cyclobutylboronates by conjugate borylation of a-alkyl,b-aryl/alkyl cyclobutenones has been successfully developed.…”

Visible‐Light‐Driven Strain‐Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

“…Finally, we explored the versatility of the boronic ester moiety in the benzo‐fused cyclobutenes, since functionalization of less strained cyclobutyl boronic esters has already been described . As depicted in Scheme , spirolactone 11 a could be quantitatively prepared by an oxidation/lactonization sequence .…”

“…Finally, we explored the versatility of the boronic ester moiety in the benzo-fused cyclobutenes, since functionalization of less strained cyclobutyl boronic esters has already been described. [8,18] As depicted in Scheme 4, spirolactone 11 a could be quantitatively prepared by an oxidation/lactonization sequence. [19] Zweifel olefination [20] or Matteson homologation [21] enabled the construction of new CÀC bonds, leading to alkene 11 b and boronic ester 11 c in good yields, respectively.…”

Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines

“…We elected to trap 4 as a sulfoxide, since this would potentially offer a stable, solid reagent from which 4 could be conveniently regenerated. 13 Therefore, 4 was trapped with methyl 4-methylbenzenesulfinate (7) to give azabicyclo[1.1.0]butyl sulfoxide 8 in 62% yield (Scheme 1A). Sulfoxide 8 was formed as a single regioisomer, showing that selective deprotonation had indeed occurred, and problems relating to polymerization did not materialize, presumably due to a fast, low temperature lithiation step.…”