Rhodium-Catalyzed Regiodivergent Synthesis of Alkylboronates via Deoxygenative Hydroboration of Aryl Ketones: Mechanism and Origin of Selectivities

Abstract

Here, we report an efficient rhodium-catalyzed deoxygenative borylation of ketones to synthesize alkylboronates, in which the regioselectivity can be switched by the choice of the ligand. The linear alkylboronates were obtained exclusively in the presence of P­( n Bu)3, and PPh2Me favored the formation of branched alkylboronates. The protocol also allows access to 1,1,2-triboronates from the readily available ketones. Mechanistic studies suggest that this Rh-catalyzed deoxygenative borylation of ketones goes through an alkene intermediate, which undergoes regiodivergent hydroboration to afford linear and branched alkylboronates. The different steric effects of PPh2Me and P­( n Bu)3 were found to be responsible for product selectivity by density functional theory calculations. The alkene intermediate can alternatively undergo sequential dehydrogenative borylation and hydroboration to deliver the triboronates.

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

“…[27][28][29] In 2020, Lisg roup conceived am etal-free version of direct carbonyl deoxyborylation reaction, [30] which was enabled by the unique partnership of the Lewis acidic bis(catecholato)diboron (B 2 cat 2 )a nd the mildly basic N,N-dimethylacetamide (DMA) (Scheme 5E). Amechanism analogous to that in Lius [25][26][27] and Zhaos [28,29] works was proposed, albeit in the absence of the metal catalyst. Of note,t he lability of catecholatoborates in the aqueous environment often induces proto-deboronation.…”

“…Interestingly,t he simple addition of alcohol (e.g., MeOH or EtOH) to the current Cu-catalyzed protocol or using ZhaosR h/PR 3 /B 2 pin 2 /HBpin catalysis completely switched the selectivity to deoxygenative hydroboration. [27][28][29] In 2020, Lisg roup conceived am etal-free version of direct carbonyl deoxyborylation reaction, [30] which was enabled by the unique partnership of the Lewis acidic bis(catecholato)diboron (B 2 cat 2 )a nd the mildly basic N,N-dimethylacetamide (DMA) (Scheme 5E). Amechanism analogous to that in Lius [25][26][27] and Zhaos [28,29] works was proposed, albeit in the absence of the metal catalyst.…”

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

“…A similar scenario could happen with the stepwise addition of pinB‐SiMe 2 Ph as the Nu 2 , achieving a deoxygenative gem ‐silylborylation on the aldehyde/ketone carbonyls ( 5.19 to 5.22 ). Interestingly, the simple addition of alcohol (e.g., MeOH or EtOH) to the current Cu‐catalyzed protocol or using Zhao's Rh/PR 3 /B 2 pin 2 /HBpin catalysis completely switched the selectivity to deoxygenative hydroboration [27–29] …”

Rhodium-Catalyzed Regioselective and Chemoselective Deoxygenative Reduction of 1,3-Diketones

“…In addition to the issue of regiocontrol, the reduction of 1,3-diketones also includes other problems, such as the semi- and over-reduction of diketones to β-hydroxy ketones, 1,3-diols, alcohols, or alkanes, further proving it to be significantly challenging. In view of our recent success in Rh-catalyzed deoxygenation and deoxygenative borylation of ketones, , we envisioned that bis­(pinacolato)­diboron (B 2 pin 2 ) might serve as an efficient ketone oxygen abstraction reagent in the presence of transition–metal catalysts to generate an α, β-unsaturated ketone intermediate, which subsequently undergoes 1,4-reduction to give the desired ketone product (Figure d), thereby offering a powerful tool to deoxygenatively reduce 1,3-diketones under mild reaction conditions.…”