Charles C. J. Loh

Exploiting Distal Reactivity of Coumarins: A Rhodium‐Catalyzed Vinylogous Asymmetric Ring‐Opening Reaction

While the utility of vinylogous enolates is well established in the setting of vinylogous aldol, Mannich, and Michael chemistries, literature reports concerning γ-reactivity are scarce for other reaction classes. Presented herein is an unprecedented example of vinylogous reactivity exemplified by the rhodium-catalyzed asymmetric ring-opening reaction of oxabicycles. This strategy also provides a powerful route to incorporate the biologically useful coumarin motif into the hydronapthalene scaffold.

Rhodium‐Catalyzed Asymmetric Cycloisomerization and Parallel Kinetic Resolution of Racemic Oxabicycles

While desymmetrizations by intermolecular asymmetric ring-opening reactions of oxabicyclic alkenes with various nucleophiles have been reported over the past two decades, the demonstration of an intramolecular variant is unknown. Reported herein is the first rhodium-catalyzed asymmetric cycloisomerization of meso-oxabicyclic alkenes tethered to bridgehead nucleophiles, thus providing access to tricyclic scaffolds through a myriad of enantioselective C-O, C-N, and C-C bond formations. Moreover, we also demonstrate a unique parallel kinetic resolution, whereby racemic oxabicycles bearing two different bridgehead nucleophiles can be resolved enantioselectively.

Benzylic Functionalization of Anthrones via the Asymmetric Ring Opening of Oxabicycles Utilizing a Fourth‐Generation Rhodium Catalytic System

While anthrones exist as privileged scaffolds in bioactive molecules, the enantioselective functionalization of anthrones is surprisingly scarce in the literature, with no asymmetric transition metal catalyzed example to date. Herein, we report the first asymmetric transition metal catalyzed benzylic functionalization of anthrones through the rhodium(I) catalyzed desymmetrization of oxabicycles. As previously developed rhodium(I) systems were found to be unsuitable for this substrate, a new robust fourth-generation [Rh(cod)OH]2 based catalytic system was developed to address synthetic challenges in this protocol.

Asymmetric Rhodium-Catalyzed C–C Activation of Cyclobutanones

Significance: C–C activation is an attractive method to functionalize strained four-membered ring systems. Zhou and Dong demonstrate the utility of allenes as a formal vinyl carbenoid in a rhodium-catalyzed asymmetric intramolecular ring expansion of cyclobutanones. Comment: An impressive substrate scope for this C–C activation protocol is demonstrated. Challenging cyclobutanone substrates such as those that are α-substituted also worked for this methodology, albeit with slightly diminished yields. General reaction: O R1

Rhodium-Catalyzed Asymmetric C–H Functionalization of Methyl Ethers

Significance: The asymmetric site-selective functionalization of unactivated sp3 C–H bonds is one of the most challenging reactions to date. Davies and co-workers demonstrated in this article the utility of trichloroethyl aryldiazoacetates as excellent substrates in the Rh-catalyzed enantioselective functionalization of methyl ethers. Comment: A wide spectrum of methyl ethers can be functionalized with trichloroethyl aryldiazoacetates with moderate and good yields and excellent enantioselectivities. In all cases, regioselectivity of the carbene insertion is on the less hindered methyl moiety. When a chiral ether was utilized, different diastereomeric products could be selectively accessed using opposite enantiomers of the chiral catalyst (matched and mismatched). General reaction:

Enantioselective and Stereodivergent Synthesis of β,β-Diaryl-α-Amino Acids

385 C . M O L I N A R O , * J . P . S C O T T , * M . S H E V L I N , * C . WI SE , A . M É N A R D , A . G I B B , E . M . J U N K E R , D . L I E BE R M A N ( M E R C K & C O . I N C . , RA H W A Y, U S A A N D M E R C K S H A R P A ND D OH M E L T D , H O D D E S D O N, U K ) Catalytic, Asymmetric and Stereodivergent Synthesis of Non-Symmetric β,β-Diaryl-α-Amino Acids J. Am. Chem. Soc. 2015, 137, 999–1006.