Copper(Ⅰ)-catalyzed diastereodivergent construction of vicinal P-chiral and C-chiral centers facilitated by dual“soft-soft”interaction

A copper(Ⅰ)-catalyzed diastereodivergent addition of phosphinothioates(HP(S)ROR')toα,β-unsaturated thioamides is disclosed,which constructs vicinal P-chiral and C-chiral centers in generally high diastereoand enantioselectivities.In this reaction,the kinetic resolution of HP(S)ROR'occurs,which affords(R)-HP(S)Ph OMe in high enantioselectivity in the addition with(R,R)-Ph-BPE as the ligand.It is found through control experiment that dual“soft-soft”interaction,indicated by both1H and31P NMR experiments,is indispensable in the present reaction.The first“soft-soft”interaction between copper(Ⅰ)catalyst and HP(S)ROR'enables facile deprotonation to generate nucleophilic[Cu]-SPROR'species.The second one between the[Cu]-SPROR'species andα,β-unsaturated thioamides facilitated the nucleophilic addition.Finally,both Michael adducts and(R)-HP(S)PhOMe are easily converted to synthetically useful compounds.

Diastereodivergent formal[4+1]cycloaddition of azoalkenes as one-carbon synthons

The first diastereodivergent formal[4+1]cycloaddition reactions of azoalkenes with p-quinone methides(pQMs)have been accomplished.The reported reaction occurred via a domino oxa-1,4-addition/1,6-addition process,allowing the use of common azoalkenes as C1 synthons.A broad range of 2,3-dihydrobenzofurans was smoothly prepared in good yields and with reversible diastereoselectivities.The steric hindrance and hydrogenbonding interaction were proposed to account for the two different modes of diastereo-control.The projected reaction features the employment of azoalkene as carbene-like C1 synthon,mild conditions,broad substrate scope and tunable diastereoselectivity.

Diastereodivergent[4+2]annulation of biphenylenes with enones via nickel(0)-catalyzed C-C bond activation

Ni(0)-catalyzed regio-and diastereodivergent[4+2]annulation of biphenylenes withα,βunsaturated ketones is described.This solvent-controlled diastereodivergent reaction integrates C-C bond cleavage of biphenylene and C=C double bond insertion selectivity,offering a mild approach to all possible diastereoisomers of 9,10-dihydrophenanthrene derivatives from the same starting materials.

Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed by N-Heterocyclic Carbene-Ni(o)

Catalytic diastereodivergent hydrosilylative enyne cyclization with high generality and broad scope was achieved using electronic ac-tivated N-heterocyclic carbene-Ni(O)as a catalyst and R_(3)SiH as silane(IPr^(Cl),syn-:anti-selectivity from up to 98:2 to 7:93 by Z=0,NH vs.NMs,R^(1)=n-pentyl).Heterocycles bearing homoallylsilane rather than vinylsilane was obtained chemoselectively.The undesired yet highly competitive reactivity was suppressed,like direct hydrosilylation of alkene and alkyne concurrently.Optionally,the homoallylsilane products could be reduced further in one-pot using IPr^(Me) as ligand and(EtO)_(3)SiH as silane under otherwise the same standard condition as the above,offering practical access to additional stereocenters and more diverse product structures from enynes.

Solvent-Regulated Diastereodivergent [3+2] Annulations of CF_(3)-Containing Morita-Baylis-Hillman Carbonates with Cyclic Sulfonimines

A solvent-regulated diastereodivergent[3+2]annulation reaction between Morita-Baylis-Hillman carbonates from aryl trifluoromethyl ketones and cyclic sulfonimines is developed under the catalysis of a modified cinchona alkaloid,furnishing diverse polycyclic products bearing vicinal quaternary stereogenic centers with outstanding enantioselectivity and moderate to high diastereoselectivity.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols under different reaction conditions.Using this strategy,two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities(up to 99%yield,95:5 er,>95:5 dr).Moreover,theoretical calculations were performed on the key transition states leading to different stereoisomers,which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions.More importantly,these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity,which demonstrated their potential applications.This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles,but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality.

NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been developed.The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents(THF or DCE).The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole andα,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst.Moreover,four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.