A novel strategy based on Cu-catalyzed (4+1) cascade annulation of terminal alkynes as one-carbon synthons with 2-(tosylmethyl)­anilines has been developed for the expeditious synthesis of 2,3-disubstituted indoles, in which in situ generations of aza-o-quinone methides and alkynyl-copper­(I) species are involved. This annulation provides an effective method for the assembly of synthetically and structurally interesting 2,3-disubstituted indoles.

A new tandem annulation of p-quinone methides (p-QMs) with ynamides is described. This cascade reaction features a unique combination of (2 + 2) annulation, retro-4π electrocyclization, and imino-Nazarov cyclization, wherein vinyl p-quinone methides (p-VQMs) as one of the key intermediates have been identified chemically. Significantly, an unusual structural reconstruction of p-QMs involving the cleavage of the C5–C6 bond and the late-stage formation of the C4–C6 bond is involved, leading to a methodology development for the construction of functionalized aminoindenes.

The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthons has been explored for the first time in a novel tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization...

A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (−)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (−)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (−)-cephalotine B with an additional C3–O–C11 oxo-bridged bond (14 steps), (−)-fortuneicyclidin B with an unprecedented C3–C10 bond (14 steps), and its 2-epimer (−)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.

We report a unique and expeditious route to synthesize 1-isochromanone derivatives through palladium catalyzed tandem Heck coupling/6-endo hydroacyloxylation cyclization between readily available ortho-halogenated benzoates and unactivated alkenes. Various 2-bromo or 2-iodo benzoates can be coupled efficiently with a broad range of alkenes to afford functionalized 1isochromanones in high yields. Significantly, this cost-efficient and easy-to-handle synthetic methodology will have great prospect application in the synthetic and medicinal chemistry.