Regio‐ and Stereoselective Synthesis of 1,1‐Diborylalkenes via Brønsted Base‐Catalyzed Mixed Diboration of Alkynyl Esters and Amides with BpinBdan

The NaOtBu‐catalyzed mixed 1,1‐diboration of terminal alkynes using the unsymmetrical diboron reagent BpinBdan (pin = pinacolato; dan = 1,8‐diaminonaphthalene) proceeds in a regio‐ and stereoselective fashion affording moderate to high yields of 1,1‐diborylalkenes bearing orthogonal boron protecting groups. It is applicable to gram‐scale synthesis without loss of yield or selectivity. The mixed 1,1‐diborylalkene products can be utilized in Suzuki–Miyaura cross‐coupling reactions which take place selectivly at the C–B site. DFT calculations suggest the NaOtBu‐catalyzed mixed 1,1‐diboration of alkynes occurs through deprotonation of the terminal alkyne, stepwise addition of BpinBdan to the terminal carbon followed by protonation with tBuOH. Experimentally observed selective formation of (Z)‐diborylalkenes is supported by our theoretical studies.


IV. Substrate Scope Experimental procedures
General procedures for products 2.
In a 10 mL thick-walled reaction tube equipped with a magnetic stirring bar, BpinBdan (59 mg, 0.2 mmol), base (2 mg, 0.02 mmol) and CH 3 CN (2 mL) were added. Then, alkynes 1 (0.24 mmol) were added and the tube was sealed with a crimped septum cap. The reaction was heated at 40 °C under argon for 5 h. The reaction mixture was then diluted with Et 2 O (4 mL) and filtered through a plug of celite (∅ 3 mm × 8 mm) in air with copious washing (Et 2 O).
The solvents were removed in vacuo, and the residue was purified by flash column chromatography on silica gel.

Experimental procedure for the synthesis of 2a on a gram scale.
In a 10 mL thick-walled reaction tube equipped with a magnetic stirring bar, BpinBdan (1.  Figure S1. GC-MS of the crude material including the main product 2a. S10 Figure S2. GC-MS of pure compound 2a.

Computational methods
DFT calculations were carried out with the Gaussian09 package. [6] Geometry optimization was performed with the B3LYP-D3 functional [7] and 6-31+G(d) basis set in MeCN solvent (using the SMD [8] solvent model). Frequency analysis was carried out at the same level to verify the stationary points as an intermediate or transition state and to obtain the thermodynamic energy corrections assuming a standard state of 1 atm and 298.15 K.
Intrinsic reaction coordinates (IRC) [9] were calculated to confirm the connection between the transition state and the correct reactant/product. Single-point calculations were carried out with the M11 functional [10] and 6-311+G(d,p) basis set in MeCN solvent (using the SMD solvent model).
Due to the different migration directions relative to the carboxyl group in intermediates 5 and 9, there are four paths to realize 1,2-migration of Bpin or Bdan moiety and generate allenylic axial chiral isomers 7 and 21. As shown in Figure 2 and Figure S7, the two paths to form 21 via transition states 19-ts and 20-ts have a slightly higher barrier than those to form 7. In the following hydrogen transfer step, the relative free energies of transition states 22-ts and 23-ts are very close to their isomers 11-ts and 13-ts given in Figure 2.

S22
In order to examine the effect of the NH interaction with t BuOH in the protonation step, the hydrogen of NH was replaced by methyl; thus a proton from t BuOH would be transferred to allenolate 24 without the NH interaction. As shown in Figure S8, 25-ts has a lower free energy than 26-ts by 2.3 kcal/mol, which indicates that the stereoselectivity is unchanged and the main product is the (Z)-diborylalkene isomer. Compared with Figure 2 and Figure   S7, the energy barrier becomes higher by about 3.0 kcal/mol for the path to form the (Z)-diborylalkene product without the NH interaction with t BuOH. In addition, the gap between the barriers of the two paths to 2a and 2a' becomes smaller. These results demonstrate that the NH interaction with t BuOH can promote the generation of (Z)-diborylalkene products, although it may not the stereoselectivity controlling factor.  Figure S8). Figure S8. A 2D NOESY spectrum of compound 28a.

IX. Single-crystal X-ray Diffraction
Crystal structure determination: Crystal of 2a, 2e, 2j, and 2m suitable for single-crystal X-ray diffraction were selected, coated in perfluoropolyether oil, and mounted on MiTeGen sample holders. Diffraction data of 2a were collected on a BRUKER X8-APEX II diffractometer with a CCD area detector using graphite-monochromated Mo-K α radiation.
Diffraction data of 2e, 2j, and 2m were collected on a Rigaku Oxford Diffraction XtaLAB Synergy diffractometer with a semiconductor HPA-detector (HyPix-6000) and multi-layer mirror monochromated Cu-K α radiation. The crystals were cooled using Oxford Cryostream low-temperature devices. Data were collected at 100 K. The images were processed and corrected for Lorentz-polarization effects and absorption as implemented in the Bruker software packages (2a) or using the CrysAlisPro software from Rigaku Oxford Diffraction (2e, 2j, 2m). The structures were solved using the intrinsic phasing method (SHELXT) [11] and Fourier expansion technique. All non-hydrogen atoms were refined in anisotropic approximation, with hydrogen atoms 'riding' in idealized positions, by full-matrix least squares against F 2 of all data, using SHELXL [12] software and the SHELXLE graphical user interface. [13] The crystal of 2m was a non-merohedral twin with domains rotated by 180.0° around real axis [100]. The twin fraction was refined to 43.7%. Diamond [14] software was used for graphical representation. Crystal data and experimental details are listed in Table   S5. Full structural information has been deposited with the Cambridge Crystallographic Data Centre. CCDC-1959477 (2a), 1969050 (2e), 1969051 (2j), and 1969052 (2m). Figure S9. Molecular structure of 2a in the solid state at 100 K. Atomic displacement ellipsoids are drawn at the 50% probability level, and H atoms are omitted for clarity. Figure S10. Molecular structure of 2e in the solid state at 100 K. Atomic displacement ellipsoids are drawn at the 50% probability level, and H atoms are omitted for clarity. Figure S11. Molecular structure of 2j in the solid state at 100 K. Atomic displacement ellipsoids are drawn at the 50% probability level, and H atoms are omitted for clarity. The hept-2-yn-1-yl moiety is disordered and only the part with the higher occupancy (75%) is shown here. Figure S12. Molecular structure of 2m in the solid state at 100 K. Atomic displacement ellipsoids are drawn at the 50% probability level, and H atoms as well as solvent molecules are omitted for clarity. Only one of two symmetrically non-equivalent molecules is shown here.