Synthesis of the C1–C10 Fragment of Madeirolide A

The synthesis of a fully elaborated C1–C10 fragment of madeirolide A has been achieved via a strategy based on a series of stereospecific processes. The concise synthetic route also features an iridium-catalyzed visible light induced radical cyclization for construction of the THP ring and a palladium-catalyzed glycosylation for formation of the α-cineruloside linkage

Rhodium-Catalyzed Tandem Addition–Cyclization–Rearrangement of Alkynylhydrazones with Organoboronic Acids

Transition metal-mediated catalysis routinely enables substrates of multiple π-systems to be efficiently coupled with various carbon nucleophiles along with simultaneous ring formation. This transformation, however, remains unexplored in connection with pericyclic processes. Reported here is a protocol for cycloalkene synthesis based on the merger of rhodium catalysis and a retro-ene reaction. The approach allows alkyne-tethered hydrazones and organoboronic acids to undergo a cascade of addition–cyclization–rearrangement reactions to provide cycloalkene products. The process is initiated by the rhodium-catalyzed addition–cyclization and completed with the allylic diazene rearrangement. The reaction can also be rendered asymmetric by using chiral diene ligands for the rhodium catalyst, whereby enantioselective addition to the CN bond establishes the CN stereocenter whose chirality is transferred to an allylic CH center via suprafacial rearrangement

Rhodium-Catalyzed Oxygenative [2 + 2] Cycloaddition of Terminal Alkynes and Imines for the Synthesis of β‑Lactams

A rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high <i>trans</i> diastereoselectivity. In the presence of a Rh­(I) catalyst and 4-picoline <i>N</i>-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate. The new method taking advantage of catalytic generation of a ketene species directly from a terminal alkyne provides a novel and efficient entry to the Staudinger synthesis of β-lactams under mild conditions

Tandem Diels–Alder and Retro-Ene Reactions of 1‑Sulfenyl- and 1‑Sulfonyl-1,3-dienes as a Traceless Route to Cyclohexenes

A pericyclic approach for the synthesis of six-membered ring structures is described. The method employs 1,3-dienes with a 1-sulfur substituent in a tandem sequence of Diels–Alder and retro-ene reactions. In this pairing of [4 + 2] cycloaddition and 1,5-sigmatropic rearrangement, 1-sulfenyl-1,3-dienes engage in Diels–Alder reactions with electron-deficient dienophiles. Subsequently, the sulfenyl group of the cycloadducts is oxidized and unmasked to form allylic sulfinic acids, which undergo sterospecific reductive transposition via sulfur dioxide extrusion. The sequence can also include an inverse electron demand Diels–Alder reaction by using a 1-sulfonyl-1,3-diene. This combination of two pericyclic events offers novel stereocontrolled access to cyclohexenes that are inaccessible via a direct [4 + 2] cycloaddition route