Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp(3))-H alkynylation and intramolecular C(sp(3))-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp(3))-H functionalizations for the assembly of multiple functionalized structures of natural products.

1-Hydroxytaxinine (1)isacytotoxic taxane diterpenoid. Its central eight-membered B-ring possesses four oxygenfunctionalizedc enters (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six-membered A-and C-rings.The densely functionalizedand intricately fused structure of 1 makes it ah ighly challenging synthetic target. Reported here is an efficient radical-based strategy for assembling 1 from A-and C-ring fragments.T he A-ring bearing an a-alkoxyacyl telluride moiety underwent intermolecular coupling with the C-ring fragment by aE t 3 B/ O 2 -promoted decarbonylative radical formation. After construction of the C8-quaternary stereocenter,apinacol coupling reaction using alow-valent titanium reagent formed the B-ring with stereoselective installation of the C1,C2-diol. Subsequent manipulations at the A-and C-rings furnished 1 in 26 total steps.

Enantioselective alkynylation of C(sp(3) )H bonds adjacent to a nitrogen atom has been achieved using only chiral p-tolyl tert-butyldimethylsilylethynyl sulfoximine and benzophenone under photo-irradiation conditions. A two-carbon alkyne unit was chemo- and enantioselectively transferred at the nitrogen-substituted methylene to produce the optically active propargylic amines of various structures. Remarkably, the NH-unprotected sulfoximine group efficiently transmits its stereochemical information to the product and functions as a traceless chiral auxiliary.

A general and practical synthetic protocol for the direct transformation of unreactive C(sp 3 )-H bonds to C(sp 3 )-CN bonds has been developed. The homolytic cleavage of the C-H bond is initiated by photo-excited benzophenone, and the resulting carbon radical subsequently reacts with tosyl cyanide to afford the corresponding nitrile in a highly efficient manner. The present methodology is widely applicable to various starting materials including ethers, alcohols, amine derivatives, alkanes, and alkylbenzenes. This newly developed C-H cyanation protocol provides a powerful tool for selective one-carbon elongation for the construction of architecturally complex molecules.

Abstract1‐Hydroxytaxinine (1) is a cytotoxic taxane diterpenoid. Its central eight‐membered B‐ring possesses four oxygen‐functionalized centers (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six‐membered A‐ and C‐rings. The densely functionalized and intricately fused structure of 1 makes it a highly challenging synthetic target. Reported here is an efficient radical‐based strategy for assembling 1 from A‐ and C‐ring fragments. The A‐ring bearing an α‐alkoxyacyl telluride moiety underwent intermolecular coupling with the C‐ring fragment by a Et3B/O2‐promoted decarbonylative radical formation. After construction of the C8‐quaternary stereocenter, a pinacol coupling reaction using a low‐valent titanium reagent formed the B‐ring with stereoselective installation of the C1,C2‐diol. Subsequent manipulations at the A‐ and C‐rings furnished 1 in 26 total steps.