Chiral Br?nsted acid-catalyzed asymmetric intermolecular[4+2]annulation of ynamides with para-quinone methides

Catalytic asymmetric transformations of ynamides have attracted considerable attention in recent years.However,most of them were limited to intramolecular reactions or required metal catalysts.Herein,a chiral Br?nsted acid-catalyzed asymmetric intermolecular[4+2]annulation of ynamides with para-quinone methides(p-QMs)is disclosed,which not only represents the first metal-free protocol for catalytic asymmetric nucleophilic addition of ynamides to electrophiles,but also constitutes the first enantioselective annulation between p-QMs and alkynes.This methodology leads to the practical synthesis of biologically important chiral 4-aryl-3,4-dihydrocoumarins and 4-aryl-coumarins.Preliminary control experiments indicate that the orthohydroxyphenyl substituted p-QMs could isomerize into ortho-quinone methides(o-QMs)in the presence of chiral catalyst,which further react with ynamides via enantioselective[4+2]annulation,to generate the chiral product.

Br■nsted acid-catalyzed asymmetric dearomatization of indolyl ynamides: Practical and enantioselective synthesis of polycyclic indolines

Catalytic asymmetric dearomatization of indoles and alkynes has received much attention in the past decade because this strategy offers an attractive and alternative way for the efficient synthesis of valuable chiral polycyclic indolines. However, these reactions have been mostly limited to transition-metal catalysts, and the related chiral Br■nsted acid catalysis has been scarcely reported. Herein, we disclose a chiral phosphoric acid-catalyzed asymmetric dearomatization of indolyl ynamides by direct activation of alkynes. This metal-free method enables the practical and atom-economical construction of an array of valuable chiral polycyclic indolines in moderate to good yields with high enantioselectivities.

Catalytic hydrative cyclization of aldehyde-ynamides with water for synthesis of medium-sized lactams

A non-noble metal catalyzed hydrative cyclization of aldehyde-ynamides for efficient and practical synthesis of medium-sized lactams(7-to 9-membered rings)is disclosed.Compared with previous hydrative cyclization for the formation of six-membered lactams(cis-form),a totally inverse diastereoselectivity(trans-form)of medium-sized lactams is observed.In addition,this protocol delivers valuable medium-sized lactams in moderate to good yields with high diastereoselectivities.Moreover,a rational mechanism to understand this inversion of diastereoselectivity is proposed based on theoretical calculations.

Trifluoromethyl radical triggered radical cyclization of N-benzoyl ynamides leading to isoindolinones

Under photocatalytic reductive conditions,trifluoromethyl radical addition onto an ynamide followed by cyclization on a benzoyl moiety produces diverse isoindolinone platforms with good yields.The selectivity of the radical cyclization,N-benzoyl vs.N-benzyl as radical acceptor and the E/Z ratio of isomers have been rationalized by modeling.

BF_3-promoted annulation of azonaphthalenes and ynamides for synthesis of benzo[e]indoles

A novel BF_(3)-promoted [3+2] annulation of azonaphthalenes and ynamides is described.This protocol provides a modular and efficient entry to functionalized amino benzo[e]indole derivatives smoothly.

Oxoarylation of ynamides with N-aryl hydroxamic acids

Ynamides are electron-rich alkynes with unique reactivities and act as flexible building blocks in organic synthesis.Therefore,the investigation for transformation of ynamides with exceptional selectivity and efficiency is attractive and interesting.Herein,we report an oxoarylation of ynamides with N-aryl hydroxamic acids.In the presence of catalytic Cu(OTf)_(2),both the terminal and internal ynamides could undergo an addition/[3,3] sigmatropic rearrangement cascade with N-aryl hydroxamic acids to achieve oxoarylation,along with providing selective entry to(ortho-amino)arylacetamides and oxindoles.Moreover,deuterium-labelling reaction and gram-scale reaction were conducted to probe the mechanism and showcase the scalability.

Awakening Sleeping Beauty:Vinyl Esters for Macrolactonization

Macrolactones play a critical role in pharmaceuticals and agrochemicals.Numerous efforts have been devoted to developing synthetic methods for them.We highlighted a recent progress for building macrocycles(≥12-membered)via bench-stable vinyl ester(VE)intermediates,which have been underdeveloped for half century.

Et2Zn-promoted β-trans-selective hydroboration of ynamide

The trans-hydroboration of alkyne represents a challenging task in organic synthesis.Reported herein is an Et2 Zn promotedβ-trans hydroboration of ynamides by using N-heterocyclic carbene(NHC)-ligated borane as boryl source.The reaction leads to a stereoselective construction of enamides bearing a valuable boryl substituent.Both aromatic and aliphatic ynamides were applicable to the reaction.Synthetic transformation of the C-B bond in the product via Suzuki-Miyaura coupling provides a simple and stereospecific route to multi-substituted enamides.Mechanistic studies were conducted and the possible mechanism was discussed.

One-pot synthesis of tetrahydroindoles via a copper catalyzed N-alkynation/[4+2] cycloaddition cascade

A CuSO_4 catalyzed ynamide formation/[4+2] cycloaddition relay reaction was achieved in one-pot.Various 4,7-cis-dihydroindolines were produced in good to high yields. The one-pot operation in conjunction with the cheap and benign copper catalysis renders this reaction highly sustainable.

Ynamide Protonation-Initiated Cis-Selective Polyene Cyclization and Reaction Mechanism

The diastereoselectivity of conventional polyene cyclization reactions is highly dependent on the configuration of the internal alkenes,where E-poly enes provide trans-decalins,while Z-polyenes offer cis-decalins.Although polyene cyclization has evolved into a reliable and widely used strategy for the construction of trans-decalin frameworks of terpene and steroid natural products,its application for cis-decalin framework is extremely challenging.