sp3 C–H Borylation Catalyzed by Iridium(III) Triboryl Complex: Comprehensive Theoretical Study of Reactivity, Regioselectivity, and Prediction of Excellent Ligand

Iridium-catalyzed C–H borylation of THF was theoretically investigated as example of sp3 C–H functionalization. DFT computations show that β-regioselective borylation occurs more easily than does α-regioselective, as reported experimentally, through oxidative addition of C–H bond to iridium­(III) species and reductive elimination of B–C bond. The reductive elimination is both a rate-determining step and a regioselectivity-determining step. The lower energy transition state (TS) of the reductive elimination of β-boryloxolane arises from the Ir···(β-oxolanyl) interaction at TS being stronger than the Ir···(α-oxolanyl) one. The Ir···(β-oxolanyl) interaction being stronger than the Ir···(α-oxolanyl) one is a result of the valence orbital energy of the α-oxolanyl group being higher than that of the β-oxolanyl group due to antibonding overlap of the valence orbital with O 2p orbital, where SOMO of oxolanyl radical is taken as valence orbital hereinafter. Reactivity of substrate decreases following the order primary (β) C–H of ethyl ether > primary C–H of n-pentane ∼ secondary (β) C–H of THF > secondary C–H of cyclopentane > secondary (α) C–H of THF ∼ secondary C–H of n-pentane > secondary (α) C–H of ethyl ether. The primary C–H bond is more reactive than the secondary one because of its smaller steric repulsion and lower energy valence orbital of the primary alkyl group. The β-C–H bond of THF is more reactive than the secondary C–H bond of cyclopentane because of valence orbital energy of the β-oxolanyl group being lower than that of the cyclopentyl group. Both steric and electronic factors are important for determining reactivity of substrate. Bidentate ligand consisting of pyridine and N-heterocyclic carbene is predicted to be better than 3,4,7,8-tetramethyl-1,10-phenanthroline used experimentally.本研究以四氢呋喃(THF)的铱催化C–H硼化反应作为sp³杂化C–H官能化的典型实例开展了理论计算研究。密度泛函理论(DFT)计算结果表明，正如实验报道的那样，β区域选择性硼化反应相较于α区域选择性硼化反应更易进行，其反应路径为C–H键对铱(III)物种的氧化加成，以及B–C键的还原消除。其中还原消除步骤既是决速步，也是区域选择性决定步。β-硼基氧杂环戊烷的还原消除过渡态(TS)能量更低，原因在于该过渡态中Ir···(β-氧杂环戊基)相互作用强于Ir···(α-氧杂环戊基)相互作用。而Ir···(β-氧杂环戊基)相互作用更强的根源在于：将氧杂环戊基自由基的单占据分子轨道(SOMO)作为价轨道时，α-氧杂环戊基的价轨道能量高于β-氧杂环戊基，这是由于α-氧杂环戊基的价轨道与O 2p轨道存在反键重叠所致。底物的反应活性遵循如下顺序：乙醚的伯(β) C–H键 > 正戊烷的伯C–H键 ≈ 四氢呋喃的仲(β) C–H键 > 环戊烷的仲C–H键 > 四氢呋喃的仲(α) C–H键 ≈ 正戊烷的仲C–H键 > 乙醚的仲(α) C–H键。伯C–H键的反应活性高于仲C–H键，这是因为伯烷基的空间位阻更小，且其价轨道能量更低。四氢呋喃的β-C–H键的反应活性高于环戊烷的仲C–H键，原因在于β-氧杂环戊基的价轨道能量低于环戊基的价轨道。空间位阻与电子效应均是决定底物反应活性的关键因素。理论预测，由吡啶与氮杂环卡宾(N-heterocyclic carbene)构成的双齿配体，其催化性能优于实验中所使用的3,4,7,8-四甲基-1,10-菲咯啉。