Communication pubs.acs.org/Organometallics
Magnesium-Catalyzed Hydroboration of Pyridines Merle Arrowsmith, Michael S. Hill,* Terrance Hadlington, Gabriele Kociok-Köhn, and Catherine Weetman Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K. S Supporting Information *
ABSTRACT: Reaction of catalytic quantities of a β-diketiminato n-butylmagnesium complex with pinacol−borane in the presence of pyridine derivatives provides facile access to borylated dihydropyridines. The reaction is applicable to a wide range of monocyclic and fused-ring pyridine derivatives and catalytic turnover is proposed to occur through a well-defined sequence of Mg−H/pyridine dearomatization and Mg− N/B−H sigma bond metathesis steps.
D
Scheme 1
earomatization of pyridine and its fused-ring derivatives can provide access to a plethora of functionalized molecules primed for further transformations.1 Although it has long been known that stoichiometric addition reactions of alkali-metal hydrides and alkyls give rise to reducing dihydropyridide derivatives,2 the harsh conditions employed and the relative instability of the dearomatized products does not necessarily lend itself to extension to a more attractive catalytic regime. Reports of homogeneous catalytic transformations of this nature are very scarce and are limited to an initial report of titanocene-based pyridine hydrosilylation by Harrod and a very recent description of a ruthenium-centered process by Nikonov and co-workers.3 Our own recent efforts have concentrated upon the use of heavier alkaline-earth elements, primarily Mg and Ca, in heterofunctionalization catalyses more conventionally the preserve of less abundant transition and rare-earth metals.4 While much of this work was inspired by previous observations in the chemistry of trivalent lanthanide derivatives, we have found that in many cases the reduced charge density of the similarly d0 divalent alkaline-earth centers results in divergent or, in many cases, complementary reactivity. For example, Diaconescu and co-workers have shown that a wide range of organometallic and hydrido group 3 and lanthanide derivatives are capable of consecutive o-CH activation and C−C coupling of N-heterocycles.5 In contrast, the β-diketiminato n-butylmagnesium complex I (Scheme 1) reacts cleanly with PhSiH3 in the presence of pyridine derivatives to yield simple dearomatized dihydropyridide species, 6 presumably through the intermediacy of the previously reported hydrido magnesium complex [HC{(Me)CN(2,6-iPr2C6H3)}2MgH]2.7 Although this dearomatization reactivity was readily extended to a variety of substituted and fused-ring pyridine derivatives, all attempts to incorporate these species into a catalytic scenario such as that illustrated where E © 2011 American Chemical Society
= R3Si (R = alkyl, aryl, hydrido) in Scheme 1 were unsuccessful.8 We have postulated that the necessary polarized Si−H/Mg−N metathesis transition state (inset, Scheme 1) is disfavored by the presence of additional strongly coordinating pyridine molecules, which effectively impede interaction with the relatively nonbasic phenylsilane. The absence of catalytic reactivity for the silane-based systems led us to turn our attention to commercially available boranes as a source of hydride in the hope that the Lewis acidic boron center would more effectively compete for access to the Mg−N bond. We have previously described that the reaction of 9-borabicyclo[3.3.1]nonane (9-BBN) with a β-diketiminato calcium diphenylamide provided clean access to a calcium hydride species which was isolated as a dialkylborohydride through interaction with a further 1 equiv of 9-BBN.9 A similar NMR-scale reaction performed in d8-toluene between the Received: August 30, 2011 Published: October 18, 2011 5556
dx.doi.org/10.1021/om2008138 | Organometallics 2011, 30, 5556−5559
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Table 1. Dearomatization−Hydroboration of Pyridine Derivatives with Pinacol−Borane Catalyzed by Compound I
a Relative to a tetrakis(trimethylsilyl)silane internal standard in C 6D6. bAfter addition of another 1 equiv of pinacol−borane and heating at 70 °C for a further 2 days. cThe solution turns dark red and red crystals form rapidly, depleting the catalyst in solution. dOn the basis of 3-methylnicotinate. e Isolated by recrystallization of the crude reaction mixture from hexanes at −30 °C. fIsolated by vacuum distillation. gThree equivalents of pinacolborane. h88% conversion of 3-cyanopyridine; 60% to N,N′,N′-{B(OCMe2)2}3-3-aminomethyl-1,2- and -1,4-dihydropyridine. 1H NMR shifts of the remaining 22% of dearomatized reaction products are attributed to partially reduced intermediates.
alternative reagent pinacol−borane (HBpin) and the βdiketiminato magnesium butyl complex I proceeded instantaneously at room temperature. The 11B NMR spectrum of this reaction mixture displayed a single resonance at around 37 ppm, ascribed to the n-butyl boronic acid pinacol ester (n BuBpin), while the 1H NMR spectrum revealed evidence for the clean formation of a single magnesium-containing compound, 1. A single 1H resonance observed at 4.71 ppm was ascribed to the methine in the β-diketiminate backbone, and a resonance with an identical relative integration at 3.9 ppm was tentatively assigned to a magnesium hydride through comparison to Jones’ previously reported and silane-derived hydride species [HC{(Me)CN(2,6- iPr2C6H3)}2MgH]2.7 A single 12H resonance ascribed to the methyl groups of the pinacol backbone was also observed to be shifted from that in the starting material to around 1.0 ppm, indicating that the HBpin had been cleanly converted to n -BuBpin by both the 11B NMR and the 1H NMR spectral data.
Although attempts to obtain analytically pure bulk samples of compound 1 were frustrated by the presence of variable quantities of the n-BuBpin byproduct, some insight into the nature of this problem and the identity of the magnesium hydride species in solution was provided by the use of DOSY NMR spectroscopy. The resonances attributed to compound 1 and the n-BuBpin byproduct displayed similar diffusion coefficients at 298 K and converged to an identical value at 218 K. We interpret these observations to indicate the formation of a labile magnesium-coordinated {n -BuHBpin}− anion in solution in a manner reminiscent of that observed in our previously reported studies of calcium amide reactivity with 9-BBN. In solution, it is likely that various magnesium and boron hydride species are in exchange, a proposal further supported by the outcome of a single-crystal X-ray study. This latter analysis resulted from a few crystals obtained from a similar reaction performed between the magnesium n-butyl species I and an excess of the HBpin reagent. Although these 5557
dx.doi.org/10.1021/om2008138 | Organometallics 2011, 30, 5556−5559
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crystals diffracted very weakly, providing only 66% of the complete data and consequently high residuals (R1 = 0.1031), the connectivity of the molecule was unambiguous and revealed a dimeric structure in which the magnesium centers are bridged by μ-Mg−H−Mg and O−B−O bridging interactions provided by the hydride and H2Bpin borohydride anions (see Figure S1 in the Supporting Information). Addition of 1 equiv of pinacol−borane (HBpin) and pyridine to a solution of I resulted in the formation of an orange solution, which provided a 1H NMR spectrum effectively identical with that observed for previously reported magnesium dihydropyridide species.6 Addition of a further 1 equiv of HBpin resulted in the observation of a new 12H singlet resonance at ca. δ 1 ppm in the 1H NMR spectrum, which was attributed to the formation of dearomatized and hydroborated pyridine (H PyBpin). This inference was confirmed by the 11B NMR spectrum, which revealed a new singlet resonance at 27.1 ppm assigned to the HPyBpin product. While representative uncatalyzed reactions of either pyridine or isoquinoline with HBpin provided little evidence, 0% (70 °C) and 3% (20 °C) conversion, respectively, for hydroboration, reactions employing a catalytic quantity of I (5−10 mol %) proceeded smoothly under mild (25−70 °C) conditions (Table 1). The reactions with quinoline and isoquinoline (Table 1, entries 11 and 12) proceeded cleanly at room temperature and low catalyst loading (5 mol %) within several hours to afford the N -Bpin1,2-dihydroquinoline derivatives in excellent yield. In contrast, hydroboration of unsubstituted pyridine and its methyl and phenyl derivatives required heating at 70 °C overnight and catalyst loadings of 10 mol % to achieve similar conversions. Mixtures of the N-borylated 1,2- and 1,4-dihydropyridines were observed, distinguishable by their characteristic methylene resonances which appeared in the 1H NMR spectra at ca. δ 4.0−4.2 and 2.6−2.9 ppm, respectively. In the cases of pyridine (entries 1a−d), 3-picoline (entry 3), and 3,5-lutidine (entry 5) the 1,4-adducts were formed as the major product (52−63%). Variation of the reaction temperature for the hydroboration of pyridine allowed the 1,4-adduct to be obtained almost quantitatively at 80 °C (entry 1a) as the thermodynamic product.6 Performing the reaction at 35 °C, however, did not provide selective conversion to the 1,2-adduct (entry 1d). Rather, an equimolar mixture of the 1,2- and 1,4-dihydropyridines was obtained. The reaction did not proceed in significant yields at lower temperature. Hydroboration of 4-picoline (entry 4) principally yielded the 1,2-dihydropicoline (81%). The formation of the 1,4-adduct as the minor product (19%) contrasts with stoichiometric reactions of compound 1 with phenylsilane and 2 equiv of 4picoline, which exclusively afforded the 1,2-dihydro-4-methylpyridide magnesium complex at 70 °C.8 Similarly, 4-phenylpyridine quantitatively yielded the 1,2-dihydropyridine, without formation of the 1,4-adduct being observed (entry 8). This may be a steric effect from the larger phenyl substituent, which prevents isomerization of the 1,2-dihydropyridide complex to the 1,4-dihydropyridide. It is also notable that hydroboration of 4-phenylpyridine occurred much faster than that of 4-picoline, suggesting a strong inductive effect of the pyridine ring substituents upon hydroboration rates. Despite successful stoichiometric dearomatization of 4-dimethylaminopyridine (4-DMAP) with phenylsilane, the reaction did not afford significant conversion under catalytic conditions (entry 13). After 3 days at 80 °C, however, examination of the 11B NMR spectrum of the crude reaction mixture showed complete
consumption of the pinacol−borane doublet resonance (δ 11B 31.6 ppm) and the formation of a BH3 quartet at δ 11B −9.0 ppm and a new singlet at δ 11 B 25.7 ppm, resulting from decomposition of the borane. Hydroboration of 2-picoline led to exclusive formation of the 1,4-dihydropicoline, albeit in moderate yield even after extensive periods of heating at 70 °C. Examination of the 11B NMR data, however, showed formation of the same pinacol− borane decomposition byproduct as observed with 4-DMAP. Increasing the reaction temperature systematically led to reduced turnover and faster degradation of the catalyst and the pinacol−borane substrate. For 2,6-dimethylpyridine the formation of the kinetic 1,2-dihydropyridine was entirely prevented and no catalysis was observed (entry 6). Similarly, no conversion to the dearomatized products was observed with 2-phenylpyridine and 2,2′-bipyridine, although a rapid color change of the latter reaction mixture to dark red and formation of highly insoluble red crystals was indicative of stoichiometric dearomatization of the substrate. The catalytic system did not show any functional group tolerance toward aldehyde or ester functionalities (entries 14 and 15). Instead of forming the dearomatized species, pinacol− borane was seen to add across the carbonyl double bond and to stoichiometrically cleave the methoxy group in the case of 3methylnicotinate. Although addition of another 1 equiv of pinacol−borane to the reaction mixture with 3-pyridinecarboxaldehyde and subsequent heating at 80 °C for several days resulted in the formation of small amounts of dearomatized products (
