Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

Abstract

Catalytic enantioselective conjunctive cross-coupling has been developed to construct tertiary alkylboronic esters. These reactions occur with good yield and enantioselectivity for a range of substrates. Mechanistic experiments reveal aspects of the catalytic cycle that allow hindered substrates to react without significant complicating side reactions.

Phosphonate-Directed Catalytic Asymmetric Hydroboration: Delivery of Boron to the More Substituted Carbon, Leading to Chiral Tertiary Benzylic Boronic Esters

“…3j,5a–b We recently reported that a variety of prochiral and chiral β,γ-unsaturated phosphonates possessing a trisubstituted alkene, one that bears only alkyl substituents, are excellent substrates for CAHB (Figure 4). 5a For example, 13 undergoes efficient catalyst-controlled diastereoselective CAHB. The use of ( R , R )- T2 leads to the formation of (2 R ,5 S )- 14 (82%, 97:3 dr); ( S , S )- T2 affords (2 S ,5 S )- 14 (81%, 98:2 dr).…”

“…We have been exploring rhodium-catalyzed, directed-catalytic asymmetric hydroborations (CAHB) of functionalized alkene substrates with the goal of obtaining multifunctional, chiral boronic ester synthons. 4,5a–b We find that several factors influence the regio- and stereochemical outcomes of these reactions; the nature of the directing group, the alkene substitution pattern, the nature of the alkene substituent and the nature of the chiral ligand each play pivotal roles. Using the TADDOL-derived phosphite T1 in combination with a common Rh(I) catalyst-precursor, the amide- and oxime ether-directed CAHB of β-aryl substituted methylidene substrates 1 and 3 result in boration at the less substituted terminus of the alkene affording γ-borylated products ( S )- 2 (71%, 96.5:3.5 er) and ( R )- 4 (70%, 95:5 er), respectively (Figure 1).…”

“…2 While an increasing variety of modern methods are available for the enantioselective preparation of primary and secondary organoboron derivatives, 3,4 fewer methods efficiently access chiral tertiary boronic esters. 5 The latter are important since they can serve as precursors to chiral tertiary alcohols and amines, and to the construction of all-carbon quaternary stereocenters via stereospecific C–B to C–C bond substitution. 1,2 The latter structural motif is common in natural products and compounds of biological interest and often presents a challenge for their synthesis.…”

Vinylidenation of Organoboronic Esters Enabled by a Pd‐Catalyzed Metallate Shift

“…Conjunctive cross‐coupling reactions involving diphosphine palladium complexes appear to occur by a low‐barrier metal‐induced metallate shift followed by reductive elimination . Because the vinylidene insertion operates with an alternate Pd complex than previously described couplings, it was of interest to learn about this new reaction pathway.…”

“…Conjunctive cross-coupling reactions involving diphosphine palladium complexes appear to occur by a low-barrier metal-induced metallate shift followed by reductive elimination. 26 Because the vinylidene insertion operates with an alternate Pd complex than previously described couplings, it was of interest to learn about this new reaction pathway. Analysis of the reaction was conducted by DFT (see Scheme 4 for description of method) and employed a complex between (η 3 -allyl)Pd(PCy 3 ) and the ‘ate’ complex as a starting point ( I-1 , the pathway involving a bis(phosphine)Pd(η 1 -allyl) is much higher in energy).…”