Metal‐Free Catalytic Boration at the β‐Position of α,β‐Unsaturated Compounds: A Challenging Asymmetric Induction

Abstract

Dedicated in memory of Lµszló Gulyµs.Enantioenriched a-chiral boron compounds were first obtained using chiral rhodium-phosphine complexes from the catalytic hydroboration of prochiral alkenes.[1] There are three reasons why metal-mediated asymmetric induction in C À B bond formation is more successful than existing methods involving interactions between the substrate and a chiral borane reagent [2] in the absence of a metal: 1) the low cost/ availability of the achiral borane reagent, 2) the milder reaction conditions, and, most importantly, 3) the possibility for optimization and maximization of the asymmetric induction by screening the chiral ligands. Considerable progress has since been made, particularly in relation to the enantioselective metal-mediated hydroboration, [3] diboration, [4] and bboration [5] of electron-deficient olefins. However, one challenge still remains to be overcome: the development of a metal-free asymmetric boron-addition reaction with achiral boron reagents.Our group has recently studied metal-mediated asymmetric conjugate borylation reactions in the presence of copper, [5c,d] palladium, [5g] nickel, [5h] and iron [5j] complexes that were modified with either chiral phosphine or carbene ligands. This field has recently been elegantly reviewed by Oestreich and co-workers, [6] and the authors conclude that asymmetric metal-free approaches to conjugate borylation might be the next pioneering step forwards. Hoveyda and coworkers recently reported an efficient metal-free b-boration of cyclic and acyclic a,b-unsaturated carbonyl groups promoted by N-heterocyclic carbenes (NHCs).[7] Mechanistic studies revealed that 10 mol % of carbene alone can activate the diboron reagent, bis(pinacolato)diboron (B 2 pin 2 ), by nucleophilic attack at one of the boron atoms (Scheme 1).After 1,4-addition of the reagent to the substrate the carbene is regenerated, this making the reaction catalytic.Attempts by Hoveyda and co-workers [7] to promote the bboration of 2-cyclohexen-1-one with PPh 3 and PCy 3 as nucleophilic reagents in the absence of a metal were unsuccessful. However, an early example by Hosomi and co-workers [8] showed that PBu 3 could induce slight conversion of benzylideneacetophenone into the b-borated ketone in the absence of the catalyst precursor CuOTf (Scheme 2).

Asymmetric Catalytic Borylation of α,β-Unsaturated Acceptors

“…In 2010, Fernández and co-workers reported the first asymmetric metal-free β-borylation using a chiral bisphosphine as an additive at 70 C (Scheme 21) [7]. Among the screened ligands, binap (L18) and t-Bu-Josiphos ligand (L19) displayed higher activities for ethyl crotonate (>99% conversion) with 77 and 88% ee values, respectively.…”

“…On the other hand, transition-metal-free, organocatalytic asymmetric β-borylation methodologies have been developed by Fernández [7] and Hoveyda [8]. These methods use chiral phosphines and N-heterocyclic carbenes (NHCs), respectively, as chiral additives.…”

Title Pages

“…The quantitative reduction of enamines with methanol under microwave irradiation 42 seems almost 'too good to be true', as does a simple, eco-friendly isomerization of allyl acetates with silica gel 43 . Note, too: the aerobic photooxidation of methylarenes with tetrabromomethane as catalyst 44 ; a simple aerobic oxidation of mercaptans in ionic liquids 45 ; a metal-free reductive conversion of ketones and aldehydes to ethers via tosylhydrazones 46 ; and a remarkable phosphine-catalyzed asymmetric boration of enones without the familiar copper catalyst 47 . A mild and environmentally friendly oxidative cleavage of β-diketones to carboxylic acids has also been achieved cleanly with hydrogen peroxide and an iodide source 48 , while the unusual β-fragmentation of 3-ethylenesulfonylamines to N-sulfonylaldimines with phenyl iodosoacetate and iodine effectively reverses a stalwart in organosynthesis: nucleophilic allylation of the CWN bond 49 .…”

Transition‐Metal‐Free Diboration Reaction by Activation of Diboron Compounds with Simple Lewis Bases

“…According to our DFT calculations carried out on bis(pinacolato)diboron and on its Lewis acid-base adduct with CH 3 O À anion, the sp 3 boron atom loses negative charge density upon the charge transfer from the Lewis base, while the sp 2 , virtually intact boron atom unambiguously gains [a] General conditions: substrate (0.5 mmol), diboron reagent (0.55 mmol), base (15 mol %), MeOH (2.5 mmol), THF (2 mL), T = 70 8C, t = 6 h. [b] As well as the "hydroborated" by-product (< 5 %), in certain cases traces of vinyl boronic esters (< 1 %) could be identified by GC-MS analysis. …”