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Easy access to nucleophilic boron through diborane to magnesium boryl metathesis

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ABSTRACT

Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the B–B bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,N′-di-isopropyl carbodiimide and by density functional theory.

No MeSH data available.


Single crystal X-ray structure of compound 12 and the calculated free energy profile for the reaction of 11 with MeI.(a) Molecular structure of 12 as determined by X-ray crystallography. Thermal ellipsoids at 40% probability level; hydrogen atoms and iso-propyl methyl groups are omitted for clarity. Selected bond distances (Å) and angles (°): Mg(1)–N(1) 2.0481(15), Mg(1)–N(2) 2.0416(16), Mg(1)–N(3) 2.0887(16), Mg(1)–I(1) 2.6567(6), N(1)–Mg(1)–N(3) 107.60(7), N(1)–Mg(1)–I(1) 123.52(5), N(2)–Mg(1)–N(1) 93.70(6), N(2)–Mg(1)–N(3) 107.37(7), N(2)–Mg(1)–I(1) 118.84(5), N(3)–Mg(1)–I(1) 104.69(5). (b) DFT calculated free energy (kcal mol−1) profile for the reaction of compound 11 with iodomethane (in toluene).
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f5: Single crystal X-ray structure of compound 12 and the calculated free energy profile for the reaction of 11 with MeI.(a) Molecular structure of 12 as determined by X-ray crystallography. Thermal ellipsoids at 40% probability level; hydrogen atoms and iso-propyl methyl groups are omitted for clarity. Selected bond distances (Å) and angles (°): Mg(1)–N(1) 2.0481(15), Mg(1)–N(2) 2.0416(16), Mg(1)–N(3) 2.0887(16), Mg(1)–I(1) 2.6567(6), N(1)–Mg(1)–N(3) 107.60(7), N(1)–Mg(1)–I(1) 123.52(5), N(2)–Mg(1)–N(1) 93.70(6), N(2)–Mg(1)–N(3) 107.37(7), N(2)–Mg(1)–I(1) 118.84(5), N(3)–Mg(1)–I(1) 104.69(5). (b) DFT calculated free energy (kcal mol−1) profile for the reaction of compound 11 with iodomethane (in toluene).

Mentions: Although the potential utility of species such as compound 1 lie in their ability to engage in reactions with organic electrophiles, reactivity studies of such lithium boryls have highlighted an ambiphilic character9. Reactions of 1 with organohalides, RX, have been shown to result in not only nucleophilic substitution at carbon to provide the desired alkyl borane but also halogen abstraction and resultant haloborane formation. DFT calculations on these systems have rationalized this reactivity as resulting from the operation of competitive thermodynamic (to provide the SN2 product) and kinetic reaction pathways50. Furthermore, the more kinetically accessible halogen abstraction pathway was deduced to be promoted by organohalides bearing heavier halogens of lower electronegativity and a higher ability to engage in hypervalent bonding. With these observations in mind, we assayed the reaction of compound 11 with iodomethane, reasoning that this substrate would provide a high potential for competitive halogen abstraction. A reaction performed in d8-toluene and monitored by 1H NMR spectroscopy provided a single new β-diketiminate compound (12) and evidenced the production of MeBpin which was observed as two singlet resonances at δ 0.32 (B-Me) and 1.01 p.p.m. (C-Me) within the first point of analysis. The corresponding 11B NMR spectrum comprised a single resonance at δ 36.9 p.p.m., which was also assigned to the formation of the product of nucleophilic iodide displacement, MeBpin (ref. 51). The constitution of the magnesium-containing side product (12) was confirmed through a further single crystal X-ray diffraction analysis as the anticipated β-diketiminato magnesium iodide (Fig. 5a), which preserves a monomeric constitution through the retention of the coordinated DMAP ligand. Although we cannot discount the possibility that the mechanism of boron methylation takes place via a radical-based pathway52, it is notable that a further reaction of compound 11 and MeI performed in the presence of the potential radical trap 9,10-dihydroanthracene provided identical conversion to compound 12 and MeBpin and evidenced no consumption of the aromatic hydrocarbon (Supplementary Fig. 14). DFT analysis of the reaction pathway (Fig. 5b) between 11 and MeI also confirmed the facility of the nucleophilic iodide displacement. The overall reaction was found to be highly exergonic (ΔGtol=−77.3 kcal mol−1) with a reaction barrier of only 8.5 kcal mol−1 presented by the SN2 transition state (TS(11–12)a; ΔGtol=+8.4 kcal mol−1) in which the boryl anion acts as an unambiguous nucleophile through a classical backside attack on the iodomethane carbon atom. This process provides an intermediate (INT(11–12); ΔGtol=−61.2 kcal mol−1) in which the Me-Bpin is coordinated to the Mg complex through one of its oxygen atoms (Mg⋯O=2.11 Å) and the iodide persists within the outer coordination sphere of the complex (Mg⋯I=5.8 Å, see Supplementary Fig. 2). Concerted coordination of iodide to magnesium and dissociation of the methyl borane product occurs with a barrier of 7.2 kcal mol−1, (TS(11–12)b; ΔGtol=−54.0 kcal mol−1), to form the ultimate product 12 (ΔGtol=−77.3 kcal mol−1).


Easy access to nucleophilic boron through diborane to magnesium boryl metathesis
Single crystal X-ray structure of compound 12 and the calculated free energy profile for the reaction of 11 with MeI.(a) Molecular structure of 12 as determined by X-ray crystallography. Thermal ellipsoids at 40% probability level; hydrogen atoms and iso-propyl methyl groups are omitted for clarity. Selected bond distances (Å) and angles (°): Mg(1)–N(1) 2.0481(15), Mg(1)–N(2) 2.0416(16), Mg(1)–N(3) 2.0887(16), Mg(1)–I(1) 2.6567(6), N(1)–Mg(1)–N(3) 107.60(7), N(1)–Mg(1)–I(1) 123.52(5), N(2)–Mg(1)–N(1) 93.70(6), N(2)–Mg(1)–N(3) 107.37(7), N(2)–Mg(1)–I(1) 118.84(5), N(3)–Mg(1)–I(1) 104.69(5). (b) DFT calculated free energy (kcal mol−1) profile for the reaction of compound 11 with iodomethane (in toluene).
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Related In: Results  -  Collection

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f5: Single crystal X-ray structure of compound 12 and the calculated free energy profile for the reaction of 11 with MeI.(a) Molecular structure of 12 as determined by X-ray crystallography. Thermal ellipsoids at 40% probability level; hydrogen atoms and iso-propyl methyl groups are omitted for clarity. Selected bond distances (Å) and angles (°): Mg(1)–N(1) 2.0481(15), Mg(1)–N(2) 2.0416(16), Mg(1)–N(3) 2.0887(16), Mg(1)–I(1) 2.6567(6), N(1)–Mg(1)–N(3) 107.60(7), N(1)–Mg(1)–I(1) 123.52(5), N(2)–Mg(1)–N(1) 93.70(6), N(2)–Mg(1)–N(3) 107.37(7), N(2)–Mg(1)–I(1) 118.84(5), N(3)–Mg(1)–I(1) 104.69(5). (b) DFT calculated free energy (kcal mol−1) profile for the reaction of compound 11 with iodomethane (in toluene).
Mentions: Although the potential utility of species such as compound 1 lie in their ability to engage in reactions with organic electrophiles, reactivity studies of such lithium boryls have highlighted an ambiphilic character9. Reactions of 1 with organohalides, RX, have been shown to result in not only nucleophilic substitution at carbon to provide the desired alkyl borane but also halogen abstraction and resultant haloborane formation. DFT calculations on these systems have rationalized this reactivity as resulting from the operation of competitive thermodynamic (to provide the SN2 product) and kinetic reaction pathways50. Furthermore, the more kinetically accessible halogen abstraction pathway was deduced to be promoted by organohalides bearing heavier halogens of lower electronegativity and a higher ability to engage in hypervalent bonding. With these observations in mind, we assayed the reaction of compound 11 with iodomethane, reasoning that this substrate would provide a high potential for competitive halogen abstraction. A reaction performed in d8-toluene and monitored by 1H NMR spectroscopy provided a single new β-diketiminate compound (12) and evidenced the production of MeBpin which was observed as two singlet resonances at δ 0.32 (B-Me) and 1.01 p.p.m. (C-Me) within the first point of analysis. The corresponding 11B NMR spectrum comprised a single resonance at δ 36.9 p.p.m., which was also assigned to the formation of the product of nucleophilic iodide displacement, MeBpin (ref. 51). The constitution of the magnesium-containing side product (12) was confirmed through a further single crystal X-ray diffraction analysis as the anticipated β-diketiminato magnesium iodide (Fig. 5a), which preserves a monomeric constitution through the retention of the coordinated DMAP ligand. Although we cannot discount the possibility that the mechanism of boron methylation takes place via a radical-based pathway52, it is notable that a further reaction of compound 11 and MeI performed in the presence of the potential radical trap 9,10-dihydroanthracene provided identical conversion to compound 12 and MeBpin and evidenced no consumption of the aromatic hydrocarbon (Supplementary Fig. 14). DFT analysis of the reaction pathway (Fig. 5b) between 11 and MeI also confirmed the facility of the nucleophilic iodide displacement. The overall reaction was found to be highly exergonic (ΔGtol=−77.3 kcal mol−1) with a reaction barrier of only 8.5 kcal mol−1 presented by the SN2 transition state (TS(11–12)a; ΔGtol=+8.4 kcal mol−1) in which the boryl anion acts as an unambiguous nucleophile through a classical backside attack on the iodomethane carbon atom. This process provides an intermediate (INT(11–12); ΔGtol=−61.2 kcal mol−1) in which the Me-Bpin is coordinated to the Mg complex through one of its oxygen atoms (Mg⋯O=2.11 Å) and the iodide persists within the outer coordination sphere of the complex (Mg⋯I=5.8 Å, see Supplementary Fig. 2). Concerted coordination of iodide to magnesium and dissociation of the methyl borane product occurs with a barrier of 7.2 kcal mol−1, (TS(11–12)b; ΔGtol=−54.0 kcal mol−1), to form the ultimate product 12 (ΔGtol=−77.3 kcal mol−1).

View Article: PubMed Central - PubMed

ABSTRACT

Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the B–B bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,N′-di-isopropyl carbodiimide and by density functional theory.

No MeSH data available.