Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic Applications

Abstract

A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B₂Pin₂) is described. The reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron reagent PinB-BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that exhibit differential reactivity. One example prepared by diboration of 1-octyne was crystallized, and its stereochemistry established by X-ray crystallography. The utility and versatility of the 1,1-diborylalkene products was demonstrated in a number of synthetic applications, including a concise synthesis of the epilepsy medication tiagabine. In addition, a synthesis of 1,1,1-triborylalkanes was accomplished through cobalt-catalyzed hydroboration of 1,1-diborylalkenes with HBPin. Deuterium-labeling and stoichiometric experiments support a mechanism involving selective insertion of an alkynylboronate to a Co-B bond of a cobalt boryl complex to form a vinylcobalt intermediate. The latter was isolated and characterized by NMR spectroscopy and X-ray crystallography. A competition experiment established that the reaction involves formation of free alkynylboronate and the two boryl substituents are not necessarily derived from the same diboron source.

Scheme 1

1,2 vs 1,1-Selectivity in Alkyne Diboration

Scheme 2

Summary of Current Methods for the Synthesis of 1,1-Diborylalkenes

Scheme 3

Proposed Mechanism for Z-Selective Hydroboration As Inspiration for the 1,1-Diboration of Terminal Alkynes

Scheme 4. Scope of the 1,1-Diboration of Terminal Alkynes with B2Pin2 and (CyAPDI)CoCH3 (1)^a

^aReaction conditions: alkyne 2 (0.50 mmol), B₂Pin₂ (0.50 mmol, 1.0 equiv), 1 (0.025 mmol, 5 mol %), toluene (0.5 mL), 23 °C. Numbers in parentheses are yields of isolated products obtained after purification by flash chromatography on silica gel. ^b0.25 mmol 2, 0.25 mmol 3, 10 mol % 1. ^c2.0 equiv 3. ^d4.0 equiv 3. ^e1.5 equiv 3. ^fThermal ellipsoids at 50% probability.

Scheme 5. Stereoselective Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes with PinB−BDan^a

^aReagents and conditions: alkyne 2 (0.50 mmol), PinB–BDan (0.50 mmol), 1 (5 mol %), THF, 50 °C, 36 h. Numbers in parentheses are yields of isolated products obtained after purification by flash chromatography on silica gel. Thermal ellipsoids in ORTEP diagram at 50% probability; hydrogen atoms except vinyl C–H omitted for clarity. Olefin geometry of products 6a, 6d, 6e, and 6g assigned by analogy to the solid-state structure.

Scheme 6

Synthesis of Tiagabine Hydrochloride via One-Pot 1,1-Diboration/Cross-Coupling

Scheme 7

Synthetic Applications of 1,1-Diborylalkenes

Scheme 8. One-Pot, Sequential 1,1-Diboration−Hydroboration of Terminal Alkynes^a

^aReaction conditions: alkyne 2 (0.50 mmol), B₂Pin₂ (0.50 mmol, 1.0 equiv), 1 (0.025 mmol, 5 mol %), toluene (0.5 mL), 23 °C; then 14 (0.025 mmol, 5 mol %), HBPin (0.50 mmol, 1.0 equiv). Numbers in parentheses are yields of isolated products after purification by flash chromatography on silica gel. ^b2 equiv of B₂Pin₂ and HBPin were used.

Scheme 9. Synthesis of Vinylcobalt Complexes, Solid-State Structure of 21b and Single-Turnover Experiments^a

^aThermal ellipsoids at 50% probability. Hydrogen atoms omitted for clarity.

Scheme 10. Competition Experiment Probing Formation of Free Alkynylboronate^a

^aReagents and conditions: (a) 1-heptyne (0.50 mmol), 1-octynyl-BPin (0.50 mmol), B₂Pin₂ (0.50 mmol), 1 (5 mol %), toluene (0.5 mL), 23 °C, 15 h.

Scheme 11

Mechanistic Possibilities for the Origin of Stereoselectivity

Scheme 12

Stereoselective Synthesis of Vinylcobalt Species 22 and Single-Turnover Experiment