Henrik Gulyás

Activation of Diboron Reagents with Bronsted Bases and Alcohols: An Experimental and Theoretical Perspective of the Organocatalytic Boron Conjugate Addition Reaction

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.

Asymmetric organocatalytic diboration of alkenes

The use of chiral alcohols to form the Lewis acid-base *RO(-)→ bis(pinacolato)diboron adduct, in situ, provides an opportunity to induce asymmetry in the organocatalytic diboration of alkenes and complements the well established transition metal-mediated enantioselective diboration.

Nucleophilic boron strikes back

It has been demonstrated that the interaction of a simple Lewis base with tetraalkoxydiboranes generates an unusual nucleophilic character in one of the boryl moieties. The interaction of amines, N-heterocyclic carbenes (NHCs), and alkoxides with a diboron reagent results in the formation of a Lewis acid–base adduct, in which the formally intact sp2 boryl moiety becomes nucleophilic. We describe in this work the application of this new type of nucleophilic boron synthon in the selective preparation of organoboranes through β-boration and diboration reactions.

Tandem β-Boration/Arylation of α,β-Unsaturated Carbonyl Compounds by Using a Single Palladium Complex To Catalyse Both Steps

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).

Catalytic 1,3-difunctionalisation of organic backbones through a highly stereoselective, one-pot, boron conjugate-addition/reduction/oxidation process.

A simple one-pot, three-step synthetic route to chiral 1,3-amino alcohols and 1,3-diols has been established. Considering the overall stereocontrol of the synthetic protocol, the first and key step is an enantioselective β-boration of α,β-unsaturated imines and ketones, respectively. The enantioselectivity provided by the Cu(I) catalyst modified with Josiphos- and Mandyphos-type ligands has been examined. The oxidative substitution of the boryl unit with a hydroxyl group proceeds with complete retention of configuration at the C(β)-atom. In parallel, the stoichiometric reduction of the imino or carbonyl group provides a second stereogenic centre. Depending on the nature of the reducing reagent, exceptionally high diastereoselectivity is achieved, especially for syn-1,3-amino alcohols and 1,3-diols.

Organocatalytic versus iron-assisted β-boration of electron-deficient olefins.

In the light of current debates surrounding sustainable and green chemistry, iron has now become an attractive alternative to the most commonly used expensive noble metals in a number of homogenous catalytic reactions, as it is abundant, inexpensive, less toxic, and environmentally more acceptable. Despite the intense interest in the homogenous catalytic applications of iron complexes, the only known examples of iron-mediated C B bond formation are the 1,4-hydroboration of 1,3-dienes to obtain linear (E)-gdisubstituted allylboranes, and the C H activation/borylation of furans and thiophenes catalyzed by a half-sandwich iron N-heterocyclic carbene complex. Consequently, we became interested in exploring the benefits of iron in the bboration of electron-deficient olefins, comparing it with the known catalytic systems of copper and nickel complexes, and in particular with the most recently developed organocatalytic systems. In this study, we focused on the bboration of a,b-unsaturated esters and imines, which are highly versatile reactions to access polyfunctionalized molecules. We started our study by exploring whether the addition of iron salts has any positive influence on the b-boration of a,b-unsaturated esters and imines with diboron reagents. Therefore, we selected bis(pinacolato)diboron (B2pin2) as the boron source, methanol as the proton source, ethylcrotonate 1 a, and (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methanamine 1 b as the substrates for the model reactions (Scheme 1). The readily available iron(II) and ironACHTUNGTRENNUNG(III) salts, Fe ACHTUNGTRENNUNG(acac)2 (acac=acetylacetonate), FeACHTUNGTRENNUNG(acac)3, FeCl2, and Fe ACHTUNGTRENNUNG(OMe)2 were selected as iron sources (2 mol % catalytic loading of iron). However, none of these salts were able to promote the b-boration reaction of 1 a and 1 b, even at 70 8C. However, the addition of a base (Cs2CO3) to the reaction medium favored the b-boration of ethylcrotonate (Table 1, entries 1– 4). The positive influence of base in this reaction was first observed in the case of the CuCl/KOAc catalyst. The catalytic system FeACHTUNGTRENNUNG(acac)2/PPh3 (Fe/PPh3 = 1:2) was also inactive, but the presence of the base, Cs2CO3, allowed the bboration of ethylcrotonate in quantitative conversions, within 6 hours (Table 1, entries 5–8). Lowering the reaction temperatures substantially diminished the reaction rate (Table 1, entries 9 and 10). The catalytic activity observed for the Fe ACHTUNGTRENNUNG(acac)2/PPh3/Cs2CO3 system can be directly compared with the corresponding PPh3/Cs2CO3 and Cs2CO3 catalysts (Table 1, entries 8, 11, and 12). The base alone provides 45 % conversion under the chosen catalytic conditions (Table 1, entry 12). Combining the base with phosphine increases the activity but the conversion is still moderate (Table 1, entry 11). The addition of the iron salt to the PPh3/ Cs2CO3 system is strikingly beneficial; this results in complete conversion (Table 1, entry 8). A similar trend has been observed for the b-boration of (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methanamine 1 b, which to the best of our knowledge, has only been b-borated with a copper catalyst modified with phosphine ligands. While Fe ACHTUNGTRENNUNG(acac)2 did not show catalytic activity, its combination with Cs2CO3 resulted in 28 % conversion (Table 2, entry 1). The benefits of the addition of base were also ob[a] A. Bonet, C. Sole, Dr. H. Guly s, Dr. E. Fern ndez Department F sica Qu mica i Inorg nica Faculty of Chemistry University Rovira i Virgili C/Marcel.l Domingo s/n (Spain) Fax: (+34) 977-559563 E-mail : mariaelena.fernandez@urv.cat henrik.gulyas@urv.cat Homepage: http://www.quimica.urv.cat/~ tecat/catalytic_ organoborane_chemistry.php Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201000826. Scheme 1. b-boration model reaction of activated olefins.

SPOs as new ligands in Rh(III) catalyzed enantioselective transfer hydrogenation

The self-assembly of Secondary Phosphine Oxides (SPOs) into anionic bidentate chelates was used to construct unique systems for metal catalyzed transfer hydrogenation of ketones in isopropanol. Chelating bidentate or tridentate ligands were formed by assembly of secondary phosphine oxides through hydrogen bonding in the presence of rhodium trichloride as demonstrated by means of NMR spectroscopy and X-ray diffraction. When a chiral version of an SPO was used in asymmetric transfer hydrogenation of isopropanol and acetophenone, an enantiomeric excess of 89% was achieved. The presence of at least two ligands in the catalytically active species was confirmed by a positive non-linear effect. DFT calculations were applied to characterize several intermediates for the isopropanol dehydrogenation to produce a rhodium hydride complex and acetone. A transition state for the hydrogen-transfer was fully characterized, which revealed that the process occurs via a concerted outer-sphere mechanism.

Highly active, chemo- and enantioselective Pt-SPO catalytic systems for the synthesis of aromatic carboxamides

Platinum complexes modified with a chiral non-racemizing SPO preligand 1 have been applied in the hydration of aromatic nitriles. [Pt(1)3Cl]Cl formed readily from Pt(COD)Cl2. The chiral secondary phosphine oxide complex showed moderate activity in the hydration of para- and meta-substituted benzonitriles, but failed in converting the ortho-substituted derivatives. The hydride complex PtH(PR2OH)(PR2O–H⋯OR2P) (PR2OH = 1) formed from Pt(PPh3)4 and 1, and the cationic complex derived from [Pt(1)3Cl]Cl via direct chloride abstraction with AgNO3 were proven to be considerably more active, allowing us to extend the scope to the hydration of ortho-substituted aromatic nitriles, including axially chiral [1,1′-binaphthalene]-2,2′-dicarbonitrile. In the hydration of the racemic dinitrile, successful kinetic resolution has been achieved. The catalysts derived from non-racemizing 1 are the first chiral transition metal–SPO complexes that provide kinetic resolution in the hydration of a racemic chiral nitrile.