Shanghai Institute of Organic Chemistry

The chemoselective [2+1] cycloaddition of difluorocarbene with conjugated enynes has been achieved. Using TMSCF2Br as the difluorocarbene precursor in the presence of a catalytic amount of n-Bu4N+Br-, the reaction proceeded smoothly in THF at 110 °C, affording a series of alkenyl-substituted difluorocyclopropenes. Subsequently, these products could be hydrolyzed in one pot to furnish the corresponding alkenyl-substituted cyclopropenones.

Discovery and application of reactive intermediates has prominently expedited the development of organic chemistry. In this respect, while ketene has been well recognized as a versatile intermediate for a wide range of transformations, practical application of difluoroketene remained virtually unrealized because of its highly reactive nature. Herein, we present a transition-metal-free approach for in situ generation of difluoroketene using difluorobromoacetylsilane as a precursor. The controlled release of chemically labile difluoroketene under mild conditions, achieved through desilylative β-elimination, establishes a foundation for successful development of its Belluš-Claisen rearrangement with allylic amines, Staudinger [2 + 2] cycloaddition with imines, [4 + 2] cycloaddition, as well as insertion into alcohols, amines, and thiols for their difluoroacetylation. A series of mechanistic experiments provide concrete support for the involvement of difluoroketene in these transformations.

Onoceroids are complex triterpenoids that arise through bidirectional cyclizations of squalene or its diepoxide derivative, followed by oxidative tailorings. By virtue of this biosynthetic sequence, many onoceroids possess unsymmetrical pseudodimeric structures, which present an unusual synthetic challenge. In this study, we describe a family-level solution to the synthesis of all known subtypes of onoceroid skeleton. A key feature in this study is the discovery of an important chelation effect that facilitates high cross-selectivity in radical C(sp 3)-C(sp 3) cross-coupling between two highly similar but distinct fragments. Combining this process with other modern radical reactions enables rapid access to more than 20 naturally occurring onoceroids. This study provides a blueprint for constructing sp 3-rich polycyclic architectures through the combination of modern synthetic paradigms.

cis-Diols play critical roles in biological systems and form key structural motifs in many pharmaceuticals and vaccines. Specific in vivo recognition of a bioactive cis-diol and subsequent functional manipulation is thus desirable but remains challenging. Here, we present a boronic acid-functionalized gold nanoparticle (AuNP) platform that accomplishes this goal by uncovering the exceptional capacity of o-carborane decorated boronic acid to disrupt P2Y12-Ticagrelor binding and by highlighting the dual stabilizing roles of o-carboranyl via carbon ligation and B-H···Au chemisorption. Furthermore, by exploiting carborane-derived counterions, we introduce a counterion-engineering strategy that decouples water solubility from the chemical vulnerability of boronic acid. The resulting intravenous nanosystem selectively neutralizes Ticagrelor, a cis-diol-containing antiplatelet drug, with high efficacy demonstrated in both mouse and pig bleeding models. This work establishes the first chemical strategy for in vivo Ticagrelor reversal and offers a broadly applicable framework for diol targeting and nanomaterial design in complex biological environments.

Comprehensive Summary Chiral allenes are privileged structural motifs found in numerous natural products and bioactive molecules, consequently, the synthesis of these scaffolds—especially polysubstituted chiral allenes—has garnered significant research interest. Among these methods, direct asymmetric functionalization of allenic sp 2 C−H bond has been recognized as a powerful strategy for the modification of allenes, enabling late‐stage functionalization (LSF) of allene‐containing bioactive compounds. In recent years, Cu(II)‐bound nitrogen‐centered radicals (NCRs) have been demonstrated to override innate radical preferences to achieve site‐selective C−H functionalizations, achieving the site‐selective C−H cyanation, arylation and alkynylation of allenes via a copper‐catalyzed radical relay process, where the HAA process exclusively occurs at sp 2 C−H bonds. Although the enantioselective version has been achieved for the reaction of 1,3‐disubstituted allenes, which afforded the chiral trisubstituted allenic nitriles with excellent enantioselectivities, the reactions of trisubstituted allenes exhibited significantly poor enantioselectivity. Herein, we report a copper‐catalyzed site‐ and enantioselective sp 2 C–H cyanation of trisubstituted allenes. This reaction was catalyzed by CuOAc and Box ligand L1 in a mixture solvent of tert ‐amyl alcohol ( t AmOH), acetone and (trifluoromethyl)benzene at –40 °C. This method efficiently afforded a broad array of tetrasubstituted axially chiral allenic nitriles in good to excellent yields with excellent enantioselectivities.

Comprehensive Summary The inherent chirality of three‐dimensional o ‐carborane derivatives arises from the substitution patterns on the icosahedral cage. This topic has received significantly less attention than the planar, axial, central, and helical chirality commonly observed in organic synthesis. Herein, we report an enantioselective B(4)–H chlorination of o ‐carboranes via a palladium‐catalyzed chiral transient directing group strategy. Reversible in situ formation of an imine directing group from 1‐(2‐formylaryl)‐ o ‐carboranes and α‐amino acids enables regio‐ and enantio‐selective activation of cage B–H bond. A variety of chiral‐at‐cage chlorinated products are obtained in moderate to good yields with enantioselectivities up to 99% ee. Mechanistic experiments together with density functional theory calculations support a trifluoroacetate‐assisted concerted metalation‐deprotonation pathway and reveal the key role of noncovalent interactions in controlling enantioselectivity.