The Suzuki-Miyaura cross-coupling reaction is one of the most widely used reactions in synthesis.

Changing behavior: A nucleophilic sp2 carbene‐type boryl moiety, formed upon interaction of tetraalkoxydiboranes and a Lewis base, can attack non‐activated CC bonds. Computational studies identify the interaction as the overlap between the strongly polarized BB σ bond (HOMO) and the antibonding π* orbital (LUMO) of the CC bond. Conceptually, the normally electrophilic boron becomes nucleophilic and forces the olefin to act as an electrophile.

The stereospecific cross-coupling of secondary boronic esters with sp2 electrophiles (Suzuki–Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel–Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C–C bond. Elimination (preceded by further oxidation in the former case) would result in rearomatization giving the coupled product stereospecifically. Initial work was examined with 2-furyllithium. Although the oxidants tested were unsuccessful, electrophiles, particularly NBS, enabled the coupling reaction to occur in good yield with a broad range of secondary and tertiary boronic esters, bearing different steric demands and functional groups (esters, azides, nitriles, alcohols, and ethers). The reaction also worked well with other electron-rich heteroaromatics and 6-membered ring aromatics provided they had donor groups in the meta position. Conditions were also found under which the B(pin)- moiety could be retained in the product, ortho to the boron substituent. This protocol, which created a new C(sp2)–C(sp3) and an adjacent C–B bond, was again applicable to a range of secondary and tertiary boronic esters. In all cases, the coupling reaction occurred with complete stereospecificity. Computational studies verified the competing processes involved and were in close agreement with the experimental observations.

Dedicated in memory of Lµszló Gulyµs.Enantioenriched a-chiral boron compounds were first obtained using chiral rhodium-phosphine complexes from the catalytic hydroboration of prochiral alkenes.[1] There are three reasons why metal-mediated asymmetric induction in C À B bond formation is more successful than existing methods involving interactions between the substrate and a chiral borane reagent [2] in the absence of a metal: 1) the low cost/ availability of the achiral borane reagent, 2) the milder reaction conditions, and, most importantly, 3) the possibility for optimization and maximization of the asymmetric induction by screening the chiral ligands. Considerable progress has since been made, particularly in relation to the enantioselective metal-mediated hydroboration, [3] diboration, [4] and bboration [5] of electron-deficient olefins. However, one challenge still remains to be overcome: the development of a metal-free asymmetric boron-addition reaction with achiral boron reagents.Our group has recently studied metal-mediated asymmetric conjugate borylation reactions in the presence of copper, [5c,d] palladium, [5g] nickel, [5h] and iron [5j] complexes that were modified with either chiral phosphine or carbene ligands. This field has recently been elegantly reviewed by Oestreich and co-workers, [6] and the authors conclude that asymmetric metal-free approaches to conjugate borylation might be the next pioneering step forwards. Hoveyda and coworkers recently reported an efficient metal-free b-boration of cyclic and acyclic a,b-unsaturated carbonyl groups promoted by N-heterocyclic carbenes (NHCs).[7] Mechanistic studies revealed that 10 mol % of carbene alone can activate the diboron reagent, bis(pinacolato)diboron (B 2 pin 2 ), by nucleophilic attack at one of the boron atoms (Scheme 1).After 1,4-addition of the reagent to the substrate the carbene is regenerated, this making the reaction catalytic.Attempts by Hoveyda and co-workers [7] to promote the bboration of 2-cyclohexen-1-one with PPh 3 and PCy 3 as nucleophilic reagents in the absence of a metal were unsuccessful. However, an early example by Hosomi and co-workers [8] showed that PBu 3 could induce slight conversion of benzylideneacetophenone into the b-borated ketone in the absence of the catalyst precursor CuOTf (Scheme 2).

Copper complexes containing chiral N-heterocyclic carbene ligands catalyze the regioselectiVe nucleophilic boryl attack at the β-carbon of R,β-unsaturated esters with enantioselectiVities up to 74% ee, depending on the nature of the ester group.

Bases play an important role in organocatalytic boron conjugate addition reactions. The sole use of MeOH and a base can efficiently transform acyclic and cyclic activated olefins into the corresponding β-borated products in the presence of diboron reagents. Inorganic and organic bases deprotonate MeOH in the presence of diboron reagents. It is concluded, on the basis of theoretical calculations, NMR spectroscopic data, and ESI-MS experiments, that the methoxide anion forms a Lewis acid-base adduct with the diboron reagent. The sp(2) B atom of the methoxide-diboron adduct gains a strongly nucleophilic character, and attacks the electron-deficient olefin. The methanol protonates the intermediate, generating the product and another methoxide anion. This appears to be the simplest method to activate diboron reagents and make them suitable for incorporation into target organic molecules.

The use of phosphines to assist the organocatalytic β-boration reaction of α,β-unsaturated carbonyl compounds has been demonstrated with a selected number of substrates. The new method eludes the use of Brönsted bases to promote the catalytic active species and PR(3) becomes essential to interact with the substrate resulting in the formation of a zwitterionic phosphonium enolate. This species can further deprotonate MeOH when B(2)pin(2) is present forming eventually the ion pair [α-(H),β-(PR(3))-ketone](+)[B(2)pin(2)·MeO](-) that is responsible for the catalysis.

Diphenyl(3-methyl-2-indolyl)phosphine (C(9)H(8)NPPh(2), 1) gives stable dimeric palladium(II) complexes that contain the phosphine in P,N-bridging coordination mode. On treating 1 with [Pd(O(2)CCH(3))(2)], the new complexes [Pd(mu-C(9)H(7)NPPh(2))(NCCH(3))](2) (2) or [Pd(mu-C(9)H(7)NPPh(2))(mu-O(2)CCH(3))](2) (3) were isolated, depending on the solvent used, acetonitrile or toluene, respectively. Further reaction of 3 with the ammonium salt of 1 led to the substitution of one carboxylate ligand to afford [Pd(mu-C(9)H(7)NPPh(2))(3)(mu-O(2)CCH(3))] (4), in which the bimetallic unit is bonded by three C(9)H(7)NPPh(2)(-) moieties and one carboxylate group. Using this methodology, [Pd(2)(mu-C(6)H(4)PPh(2))(2)(mu-C(9)H(7)NPPh(2))(mu-O(2)CCX(3))] (X=H (7); X=F (8)) were synthesised from the ortho-metalated compounds [Pd(C(6)H(4)PPh(2))(mu-O(2)CCX(3))](2) (X=H (5); X=F (6)). Complexes 3, 4, 7, and 8 have been found to be active in the catalytic beta-boration of alpha,beta-unsaturated esters and ketones under mild reaction conditions. Hindrance of the carbonyl moiety has an influence on the reaction rate, but quantitative conversion was achieved in many cases. More remarkably, when aryl bromides were added to the reaction media, complex 7 induced a highly successful consecutive beta-boration/cross-coupling reaction with dimethyl acrylamide as the substrate (99% conversion, 89% isolated yield).