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[reaction: see text] Benzylboranes are noticeably uncommon partners within Suzuki-Miyaura coupling reactions. B-Benzyl-9-BBN was successfully coupled to a range of aryl/heteroaryl bromides, chlorides, and triflates to give pharmacologically important methylene-linked biaryl structures. Activated, deactivated, and sterically hindered substrates were successfully coupled in high yield using Pd(PPh(3))(4) or Pd(OAc)(2) with SPhos as the catalyst system.

The first racemic synthesis of the non-proteinogenic amino acid (2S,3R,4R)-4-hydroxy-3-methylproline (1) has been achieved via iodolactonisation of an unnatural amino acid derivative 4. The relative stereochemistry was derived from an efficient silicon assisted aza-[2,3]-Wittig sigmatropic rearrangement of 2.

The inclusion of a C-2 trialkylsilyl substituent into allylic amine precursors allows the base-induced aza-[2,3]-Wittig sigmatropic rearrangement to proceed in excellent yield and diastereoselectivity. The rearrangement precursors require a carbonyl-based nitrogen protecting group that must be stable to the excess of strong base required for the reaction. The N-Boc and N-benzoyl group are very good at stabilizing the product anion and initiating deprotonation. The migrating groups (G) need to stabilize the intial anion by resonance and require G-CH3 pKa > 22 in order for the initial anion to be reactive enough for rearrangement. Products 7, 20b−d,f,g, and 23 are formed with high (10−20:1) anti diastereoselectivity. Product 23 containing the morpholine amide group is useful for preparing other carbonyl derivatives.

The mild and high yielding protodesilylation of C-2 trialkylsilyl terminal alkenes can be effected via a hydroboration–Peterson elimination protocol or, in the case of the phenyldimethylsilyl analogues, a one pot procedure using t-BuOK–18-C-6–TBAF can be used.