N-Heterocyclic Carbene Adducts of Alkynyl Functionalized 1,3,2-Dithioborolanes

Alkynyl functionalized boron compounds are versatile intermediates in the areas of medicinal chemistry, materials science, and optical materials. In particular, alkynyl boronate esters [R1−C≡C−B(OR2)2] are of interest since they provide reactivity at both the alkyne entity, with retention of the B−C bond or alkyne transfer to electrophilic substrates with scission of the latter. The boron atom is commonly well stabilized due to (i) the extraordinary strength of two B−O bonds, and (ii) the chelate effect exerted by a bifunctional alcohol. We reasoned that the replacement of a B−O for a B−S bond would lead to higher reactivity and post-functionalization in the resulting alkynyl boronate thioesters [R1−C≡C−B(S2X)]. Access to this poorly investigated class of compounds starts form chloro dithioborolane cyclo-Cl−B(S2C2H4) as a representative example. Whereas syntheses of three coordinate alkynyl boronate thioesters [R1−C≡C−B(S2X)] proved to be ineffective, the reactions of NHC-adducts (NHC = N-heterocyclic carbene) of cyclo-Cl-B(S2C2H4) afforded the alkyne substituted thioboronate esters in good yield. The products NHC−B(S2C2H4)(C≡C-R1) are remarkably stable towards water and air, which suggests their use as boron-based building blocks for applications akin to oxygen-based boronate esters.


Results
Since the series of compounds 4 could be prepared in acceptable yields (50%-65%) from halogenated 1,3,2-benzodithiaborole, we attempted to employ the established synthetic methodology for our target molecules 5 [27]. In analogous fashion, we reacted chloro dithiaborolane 6 [28] with a wide selection of silylated and stannylated alkynes. In contrast to the synthesis of compounds 4, the 11 B-NMR spectra (NMR = nuclear magnetic resonance)of the crude product only showed various broad signals in the range of 10-70 ppm, and the isolation of single compounds by sublimation or crystallization proved ineffective. Similar results were obtained when 6 was reacted with alkynyl organometallic reagents of more electropositive metals. Reactions performed with the alkynyl lithium reagents R−C≡C−Li (R = SiMe3 or Ph) in toluene (at ambient temperature or −78 °C) gave inseparable mixtures, while Grignard reagents of type R−C≡C−MgX (R = SiMe3 or Ph, X = Cl) in etherical solvents [Et2O, THF (tetrahydrofuran) -at ambient temperature or −78 °C] gave even worse results. In part, the latter fact can be rationalized based on decomposition reactions of 6 in etherical solvents observed in the absence of Grignard reagents (i.e., t½ ca. 5 min in Et2O at ambient temperature). Since nucleophilic substitution reactions at boron are known to proceed with higher selectivity for four-coordinate vs. three-coordinate boron compounds, borolane 6 was reacted with representative N-heterocyclic carbenes 7 as strong σ-donor ligands to form the borane adducts 8 [29].

Results
Since the series of compounds 4 could be prepared in acceptable yields (50%-65%) from halogenated 1,3,2-benzodithiaborole, we attempted to employ the established synthetic methodology for our target molecules 5 [27]. In analogous fashion, we reacted chloro dithiaborolane 6 [28] with a wide selection of silylated and stannylated alkynes. In contrast to the synthesis of compounds 4, the 11 B-NMR spectra (NMR = nuclear magnetic resonance)of the crude product only showed various broad signals in the range of 10-70 ppm, and the isolation of single compounds by sublimation or crystallization proved ineffective. Similar results were obtained when 6 was reacted with alkynyl organometallic reagents of more electropositive metals. Reactions performed with the alkynyl lithium reagents R−C≡C−Li (R = SiMe3 or Ph) in toluene (at ambient temperature or −78 °C) gave inseparable mixtures, while Grignard reagents of type R−C≡C−MgX (R = SiMe3 or Ph, X = Cl) in etherical solvents [Et2O, THF (tetrahydrofuran) -at ambient temperature or −78 °C] gave even worse results. In part, the latter fact can be rationalized based on decomposition reactions of 6 in etherical solvents observed in the absence of Grignard reagents (i.e., t½ ca. 5 min in Et2O at ambient temperature). Since nucleophilic substitution reactions at boron are known to proceed with higher selectivity for four-coordinate vs. three-coordinate boron compounds, borolane 6 was reacted with representative N-heterocyclic carbenes 7 as strong σ-donor ligands to form the borane adducts 8 [29]. The reactions of 6 with 7 afforded the adducts 8 as colorless, moisture-sensitive solids in analytically pure form. The 11 B-NMR signals show a strong high field shift expected for a change from a three-coordinate boron atom in 6 [δ( 11 B) = 62.9 ppm] to four-fold coordination at boron [δ( 11 B) = 4.6 ppm (8a), 5.5 ppm (8b)]. X-ray crystallographic analysis for 8a confirmed the bond connectivity, Figure 1i. The ethylene moiety C2H4 in the borolane entity of the products 8 shows only one set of Scheme 2. Synthetic routes towards alkynyl 1,3,2-dithiaborolanes.

Results
Since the series of compounds 4 could be prepared in acceptable yields (50%-65%) from halogenated 1,3,2-benzodithiaborole, we attempted to employ the established synthetic methodology for our target molecules 5 [27]. In analogous fashion, we reacted chloro dithiaborolane 6 [28] with a wide selection of silylated and stannylated alkynes. In contrast to the synthesis of compounds 4, the 11 B-NMR spectra (NMR = nuclear magnetic resonance)of the crude product only showed various broad signals in the range of 10-70 ppm, and the isolation of single compounds by sublimation or crystallization proved ineffective. Similar results were obtained when 6 was reacted with alkynyl organometallic reagents of more electropositive metals. Reactions performed with the alkynyl lithium reagents R−C≡C−Li (R = SiMe 3 or Ph) in toluene (at ambient temperature or −78 • C) gave inseparable mixtures, while Grignard reagents of type R−C≡C−MgX (R = SiMe 3 or Ph, X = Cl) in etherical solvents [Et 2 O, THF (tetrahydrofuran) -at ambient temperature or −78 • C] gave even worse results. In part, the latter fact can be rationalized based on decomposition reactions of 6 in etherical solvents observed in the absence of Grignard reagents (i.e., t 1 2 ca. 5 min in Et 2 O at ambient temperature). Since nucleophilic substitution reactions at boron are known to proceed with higher selectivity for four-coordinate vs. three-coordinate boron compounds, borolane 6 was reacted with representative N-heterocyclic carbenes 7 as strong σ-donor ligands to form the borane adducts 8 [29].
The reactions of 6 with 7 afforded the adducts 8 as colorless, moisture-sensitive solids in analytically pure form. The 11 B-NMR signals show a strong high field shift expected for a change from a three-coordinate boron atom in 6 [δ( 11 B) = 62.9 ppm] to four-fold coordination at boron [δ( 11 B) = 4.6 ppm (8a), 5.5 ppm (8b)]. X-ray crystallographic analysis for 8a confirmed the bond connectivity, Figure 1i. The ethylene moiety C 2 H 4 in the borolane entity of the products 8 shows only one set of protons appearing as a singlet, although the five-membered ring in the molecular structure of 8a displays half-chair conformation, and diastereotopic protons would be expected in the 1 H-NMR spectrum. This is remarkable since the singlet of the ethylene moietyC 2 H 4 is split up to two sets of diastereotopic protons in the final products 9 upon introduction of the alkynyl moiety (vide infra). We assumed a dynamic process leading to equivalent proton signals on the NMR-scale. A proposed mechanism is the dissociation of chloride in adducts 8 to give three-coordinate borenium cations of type NHC−B(S 2 C 2 H 4 ) + in low concentration, in which the ethylene protons can rapidly be equilibrated. [30,31] Variable temperature 1 H-NMR experiments (CDCl 3 , −50 • C); however, did not lead to a splitting of the singlet. The 11 B-NMR did not reveal any indication of borenium cations, which commonly give broad signals in the low field region. In part, our hypothesis is rationalized based on the mentioned singlet splitting upon substitution of chloride for the alkynyl entity, the latter of which is a poor leaving group. Reactions of NHC-adducts 8 were performed with ethynyl magnesium bromide (H−C≡C−MgBr) as a representative alkyne nucleophile. The salt elimination reactions proceeded with high selectivity and afforded the ethynyl functionalized 1,3,2-dithiaborolanes 9 as colorless solids in good yield. 11 B-NMR spectroscopy indicated a significant high field shift upon replacement of chlorine for the ethynyl entity (i.e., 4.6 ppm (8a) → −11.1 ppm (9a), and 5.5 ppm (8b) → −11.5 ppm (9b)). The presence of ethynyl entities in the products 9 is also evident from the IR spectra (IR = infrared), in which diagnostic bands for the γ(C−H) (3220-3310 cm −1 ) and γ(C≡CH) (~2044 cm −1 ) appear and indicated the introduction of a terminal alkyne moiety. X-ray crystallographic analysis for 9a and 9b gave further insight into their structures, Figure 1ii,iii. protons appearing as a singlet, although the five-membered ring in the molecular structure of 8a displays half-chair conformation, and diastereotopic protons would be expected in the 1 H-NMR spectrum. This is remarkable since the singlet of the ethylene moietyC2H4is split up to two sets of diastereotopic protons in the final products 9 upon introduction of the alkynyl moiety (vide infra).

Discussion
In an attempt to expand the scope of alkynyl borate thioesters [R 1 −C≡C−B(S 2 X)] from currently known compounds 4 with an aromatic backbone, we applied established routes to produce the novel alkynyl borate thioesters 5 with a saturated, aliphatic backbone. However, reactions starting from chloro dithioborolane 6 proved to be ineffective and gave inseparable mixtures of various products, as indicated by 11 B-NMR spectroscopy of crude products. In contrast, adducts of 6 with N-heterocyclic carbenes (8) selectively react with ethynyl magnesium bromide (H−C≡C−MgBr) to afford alkynyl substituted adducts of dithioborolanes (9) with the aliphatic backbone in good yield. The products 9 appeared remarkably stable in air and even tolerated the work-up at aqueous conditions, which is an important aspect for future facile applications. In particular, the stability of the B−S bonds towards hydrolytic cleavage is noteworthy. Future investigation of compounds 9 will focus on the methods to further functionalize the B−S bonds with moieties of interest related to applications in materials science.

Analytical Methods
NMR spectra were recorded on Bruker Avance II-300, Avance III-HD, Avance III-400, and AVII-600. The chemical shifts (δ) are reported in parts per million (ppm). The residual solvent peak (CHCl 3 , δ = 7.26 ppm) was used for referencing of the 1 H spectra. The 13 C spectra were internally calibrated by using the 13

Compound 8a
IiPr (7a, 400 mg, 2.63 mmol) in toluene (50 mL) was added dropwise to a solution of chloro dithioborolane (6, 450 mg, 3.28 mmol) in toluene (25 mL) at 0 • C. After stirring for 10 min at room temperature, the reaction mixture was dried in vacuo. The rose solid was dissolved in THF (tetrahydrofuran, 5 mL) and precipitated with pentane (20 mL). After filtration and drying in vacuo the product was obtained as a light rose solid (65% yield). Crystals suitable for X-ray crystallography were obtained by slow solvent diffusion of hexane into a solution of the product in toluene. 1

Compound 8b
IMes (7b, 1.61 g, 5.28 mmol) in toluene (15 mL) was added to a solution of chloro dithioborolane (6, 730 mg, 5.28 mmol) in toluene (10 mL) at 0 • C. A bright yellowish solid was precipitated. The reaction mixture was stirred for 30 min at room temperature. After filtration, washing with toluene (30 mL) and subsequent drying in vacuo, the product was obtained as a white solid (93% yield). If required, further purification can be performed by slow diffusion of pentane into a solution of the crude product in CHCl 3 . 1

Compound 9a
Ethynyl magnesium bromide (H−C≡C−MgBr, 1.52 mL, 0.5 M in THF, 0.76 mmol) was added dropwise to a solution of compound 8a (200 mg, 0.69 mmol) in THF (20 mL) at 0 • C. After stirring for 15 min at 0 • C and 1 h at room temperature the reaction mixture was dried in vacuo. The remaining solids were dissolved in DCM (20 mL) and washed with distilled water (3 × 20 mL). The organic phase was dried over MgSO 4 , filtrated, and dried to yield the product as a light beige solid (75%). Crystals suitable for X-ray crystallography were obtained by storing a solution of the product in toluene at −30 • C. 1

Compound 9b
Ethynyl magnesium bromide (H−C≡C−MgBr, 6.4 mL, 0.5 M in THF, 3.2 mmol) was added dropwise to a solution of compound 8b (1.28 g, 2.9 mmol) in THF (80 mL) at 0 • C. After stirring for 30 min at 0 • C and 1 h at room temperature the reaction mixture was dried in vacuo. The remaining solids were dissolved in DCM (dichloromethane, 150 mL) and washed with distilled water (3 × 150 mL). The organic phase was dried over MgSO 4 , filtrated, and dried to yield the product as a beige solid (71%). Crystals suitable for X-ray crystallography were obtained by gas phase diffusion of pentane into a solution of the product in CDCl 3 . 1  Funding: This research was funded by the "Fonds der Chemischen Industrie (FCI)" and the "Deutsche Forschungsgemeinschaft DFG". Both organizations are highly acknowledged for their generous financial support of the research. We also express our thanks to the "Publikationsfonds der TU Braunschweig" for the payment of the costs for the publication.