Pd-Catalyzed, Cu(I)-Mediated Cross-Couplings of Bisarylthiocyclobutenediones with Boronic Acids and Organostannanes

Abstract

Bisarylthiocyclobutenedione 7 reacted smoothly with a variety of both organostannanes and (hetero) aryl boronic acids in the presence of a catalytic amount of Pd and a stoichiometric amount of CuTC, to produce symmetrical disubstituted cyclobutenediones in yields that range from 37 to 94% (18 examples).Over the last three decades, various research groups have demonstrated the remarkable versatility of cyclobutenedione 1 and squaric acid ester derivatives 2 in the synthesis of organic compounds. Particularly, the groups of Liebeskind, 1 Moore, 2 Paquette, 3 and Danheiser 4 have been very active in this area.Starting from either 1 or 2, a wide variety of different compounds have been prepared, including triquinanes 3, 3a angularly-fused aromatic systems 4 ,5 bisquaryls 5 ,6 and 2-pyrones 6 7 just to mention a few (Figure 1).Squaric acid derivatives have also been used as ion sensors, 8 ligands, 9 and to prepare cyclo [n]carbons. 10 E-mail: eduardop@quijote.ugto.mx. † Universidad de Guanajuato ‡ Emory University Supporting Information Available: Experimental procedures and compound characterization data, copies of the NMR spectra of the compounds prepared. This material is available free of charge via the Internet at http://pubs.acs.org. Accordingly, the need for new protocols that allow for a practical functionalization of the 3 and 4 positions becomes evident. NIH Public AccessTo date, there are several reports in the literature describing the introduction of simple alkyl, aryl, heteroaryl, alkynyl, and alkenyl 11 functional groups in those positions of cyclobutenedione. However, they require the use of highly-reactive Grignard or organolithium derivatives which limits the functional groups that can withstand these reaction conditions. Few milder transition metal-mediated methods to prepare such derivatives have been reported. Namely, Knochel et al. reported the reaction of 3,4-dichlorocyclobutendione and zinc-copper reagents. 12 Likewise, Liebeskind disclosed an efficient synthesis of 3-(tri-n-butylstannyl)-3-cyclobutene-1,2-dione. This stannylcyclobutenedione underwent cross-couplings with organic iodides and triflates catalyzed by the PhCH 2 ClPd(PPh 3 ) 2 /CuI system. 1k,6,13 The same group reported the Stille couplings of monohalocyclobutenediones with organostannanes. 14 Against this background, we decided to explore the use of the palladium-catalyzed, coppermediated cross-couplings of thioorganics with both organostannanes and boronic acids 15 to develop a mild protocol to functionalize the vinyl positions of cyclobutenedione with both aryl and heteroaryl groups.Bisthiocyclobutenediones 7-9 where prepared in order to study the influence of the substituent on sulfur in the cross-couplings. Thus, the corresponding thiols were reacted with 3,4-dichlorocyclobutene-1,2-dione 16 10 in the presence of triethylamine (Scheme 1).Thiocyclobutenediones 7-9 were obtained in a straightforward manner as stable yellow powders which could be handled in air with no evident signs of decomposition even after several w...

Ruthenium‐ and Rhodium‐Catalyzed Strain‐Driven Cleavage and Reconstruction of the C–C Bond

“…[72] In particular, Liebeskind, Moore, Paquette, and Danheiser have been very active in this area. [73] The conversion of cyclobutenediones into quinones [74] and 5-alkylidene-2-cyclopentene-1,4-diones [75] by using a stoichiometric amount of the transition metal complex to form a (maleoyl)metal intermediate has been studied in detail. However, neither a transformation of cyclobutenediones catalyzed by transition metal complexes nor a synthetic reaction that proceeds through a metallacyclopentenedione or metallacyclobutenone intermediate, instead of a (maleoyl)metal intermediate, has been reported.…”

The Liebeskind–Srogl CC Cross‐Coupling Reaction

“…[30] In a subsequent step, the cyclobutadienone ring was coupled with boronic acids or organostannanes at the thio-substituted carbon atom in the presence of a stoichiometric quantity of a copper(I) carboxylate to form the corresponding bisaryl cyclobutadienones 3 in moderate to excellent yields (44-90 %; Scheme 14 b). [30,31]…”

Copper‐Catalyzed CC Coupling of Thiol Esters and Boronic Acids under Aerobic Conditions

“…[8] In the past few years the usefulness of this Pd-catalyzed, Cu I -mediated C À C cross-coupling method in the absence of a base (generally referred to as Liebeskind-Srogl reaction) [9] has been explored. Successful CÀC bond formation with either boronic acids or organostannanes has been achieved for a wide variety of thioorganic starting materials such as peptidylthiol esters, [10] heteroaromatic thioethers, [11] benzylthiocyanates, [12] thioalkynes, [13] bis(arylthiobutenediones), [14] methyl thiopseudourea derivatives, [15] and cyclic thioamides. [16] Two recent applications of the Liebeskind-Srogl ketone synthesis for the preparation of the natural products (À)-d-erythro-sphingosine [17] and litseaverticillol B [18] are highlighted in Scheme 2.…”

“…[6] reaction conditions. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] In contrast, the novel Cu-catalyzed protocol depends solely on an active Cu species without the need for a Pd source. Both the absence of Pd in the catalytic sequence and the lack of any precedent for oxidative addition of the thiol ester to Cu I point to a mechanistically unparalleled system for the construction of CÀC bonds.…”