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A novel synthetic route was developed for the construction of chiral cis-vicinal halohydrins derivatives through Ir/f-phamidol-catalysed asymmetric hydrogenation of corresponding α-halogenated ketones with high yields (up to 99% yield), excellent diastereoselectivities (>20 : 1 dr), enantioselectivities (up to 99% ee), and high substrate catalyst ratio (S/C = 1000). [ABSTRACT FROM AUTHOR]

Catalytic asymmetric synthesis of polysubstituted chiral cyclopropane presents a significant challenge in organic synthesis due to the difficulty in enantioselective control. Here we report a rhodium-catalyzed highly chemo-, regio- and enantioselective hydroformylation of trisubstituted cyclopropenes affording chiral quaternary cyclopropanes. Importantly, the easy made sterically bulky ligand L1 can effectively suppress hydrogenation and decomposition reactions and give quaternary cyclopropanes with high regio- and enantioselectivities for both aryl and alkyl functionalized substrates. Control experiments and computational studies reveal the sterically hindered well-defined chiral pocket instead of the substrates bearing electron-withdrawing diester groups is important for controlling the enantioselectivity and regioselectivity. Scale-up reaction and follow-up diverse transformations are also presented. Density Functional theory (DFT) computations suggest that the regio- and enantio-selectivities originate from the cyclopropene insertion to the Rh-H bond. The high regioselectivity is found to benefit from the presence of more efficient noncovalent interactions (NCIs) manifesting in the form of C–H···Cl, C–H···N, and l.p(Cl)···π contacts. Transition-metal-catalyzed asymmetric hydroformylation represents an atom-economic and clean approach for preparation of chiral aldehydes with high efficiency. Herein, the authors report rhodium-catalyzed highly chemo-, regio- and enantioselective hydroformylation of trisubstituted cyclopropenes affording chiral quaternary cyclopropanes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Transition metal‐catalyzed asymmetric transfer hydrogenation has been proven to be a powerful approach for the synthesis of chiral alcohols. Herein, a highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene‐tethered TsDPEN‐based Rh(III) catalyst has been successfully developed, and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) with high yields and enantioselectivities. With this method, the asymmetric reduction of 7,8‐difluorodibenzo[b,e]thiepin‐11(6H)‐one has been realized, providing the key intermediate of baloxavir marboxil with >99% yield and >99% ee at a substrate/catalyst molar ratio of 1000. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Transition metal‐catalyzed asymmetric transfer hydrogenation has been proven to be a powerful approach for the synthesis of chiral alcohols. Herein, a highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene‐tethered TsDPEN‐based Rh(III) catalyst has been successfully developed, and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) with high yields and enantioselectivities. With this method, the asymmetric reduction of 7,8‐difluorodibenzo[b,e]thiepin‐11(6H)‐one has been realized, providing the key intermediate of baloxavir marboxil with >99% yield and >99% ee at a substrate/catalyst molar ratio of 1000. [ABSTRACT FROM AUTHOR]

Hydroformylation (HF) or isomerization-hydroformylation (ISO-HF) represents the most direct and practical route for producing aldehydes on an industrial scale. To resolve the issues of low activity, low linear/branched ( l/b ) ratio, and low stability in HF and ISO-HF, we herein reported a class of spirocyclic diphosphites. Notably, the ligand termed O -SDPhite afforded excellent catalytic activity and regioselectivity for the HF of various olefins. Excellent l/b ratio and an unprecedented turnover number of up to 17,620,000 were achieved. O -SDPhite was also found to be effective in the regioselective ISO-HF of the industrially related cheap and abundant C4 Raffinates to n -valeraldehyde produced on a multimillion-ton scale. The reaction with O -SDPhite, superior to that of benchmark Biphephos, was continuously operated for 41 days and afforded an average 38.6 l/b ratio (31 days and 14.7 l/b ratio for Biphephos).