Transition Metal-Free Regio- and Stereo-Selective trans Hydroboration of 1,3-Diynes: A Phosphine-Catalyzed Access to (E)-1-Boryl-1,3-Enynes

Abstract

We report a transition metal-free, regio- and stereo-selective, phosphine-catalyzed method for the trans hydroboration of 1,3-diynes with pinacolborane that affords (E)-1-boryl-1,3-enynes. The reaction proceeds with excellent selectivity for boron addition to the external carbon of the 1,3-diyne framework as unambiguously established by NMR and X-ray crystallographic studies. The reaction displays a broad substrate scope including unsymmetrical diynes to generate products in high yield (up to 95 %). Experimental and theoretical studies suggest that phosphine attack on the alkyne is a key process in the catalytic cycle.

Keywords: enediyne; enyne; hydroboration; organocatalytic; stereoselective.

Scheme 1

Strategies for hydroboration of 1,3‐diynes.

Figure 1

Molecular structures of enyne boronates 2 g, 2 j, and 2 q.

Scheme 2

Substrate scope. Reaction conditions: 1 (0.25 mmol), n‐Bu₃P (0.025 mmol), HBpin (0.3 mmol), solvent, 16 h, 100 °C. ^[a] 24 h. Isolated yields are reported and E/Z ratios based on GC‐MS.

Scheme 3

Substrate scope. Reaction conditions: 1 (0.25 mmol), n‐Bu₃P (0.025 mmol), HBpin (0.3 mmol), solvent, 16 h, 100 °C. ^[a] E/Z ratio based on ¹H NMR. Isolated yields are reported and E/Z ratios based on GC‐MS.

Scheme 4

Synthetic transformation of enyne boronates.

Scheme 5

Proposed catalytic cycle.

Scheme 6

DFT calculations at the M06‐2x/6‐31(d,p) level of theory. (A) Pathway leading to key intermediate D. (B) Pathway that differentiates trans versus cis hydroboration products. Energy profiles were calculated for the phosphine‐catalyzed trans hydroboration of diyne 1 a on the basis of the catalytic cycle shown in Scheme 5. Relative free energies and electronic energies (in parentheses) are given in kcal/mol. The black colored pathway is for the trans product and blue is for the cis product.

Scheme 7

The relative stability of the four different isomers was calculated for the phosphine adduct of the unsymmetrical diyne 1 ad. Relative free energies and electronic energies (in parentheses) are given in kcal/mol.

Figure 2

³¹P{¹H} (121 MHz, scale in ppm) spectra of: (top) n‐Bu₃P and (bottom) n‐Bu₃P (0.1 mmol) and 1q (0.1 mmol) in toluene‐d₈ after 3 days at rt.

Figure 3

LIFDI‐HRMS (m/z) of n‐Bu₃P (0.1 mmol) and 1 q (0.1 mmol) in toluene‐d₈ after 3 days at rt. The mass of several adducts of the substrates are marked with the calculated values in parentheses.