CuI-catalyzed C1-alkynylation of tetrahydroisoquinolines (THIQs) by A3 reaction with tunable iminium ions.

A CuI-catalyzed A(3) (amines, aldehydes and alkynes) reaction of tetrahydroisoquinolines (THIQs), aldehydes, and alkynes to give C1-alkynylated THIQ products (endo-yne-THIQs) was developed. This redox neutral C1-alkynylation of THIQs, which was conducted under mild conditions, has a broad scope for the used aldehydes and alkynes. It was proposed that the A(3) reaction first generates in situ exo-iminium ions, which then isomerize to endo-iminium ions and react with copper acetylides to give the endo alkynylated THIQs (endo-yne-THIQs).

Mild-condition synthesis of allenes from alkynes and aldehydes mediated by tetrahydroisoquinoline (THIQ).

A practical 1,2,3,4-tetrahydroisoquinoline (THIQ)-mediated synthesis of 1,3-disubstituted allenes from terminal alkynes and aldehydes under mild conditions in the presence of CuBr first and then ZnI2 was reported. This telescoped allene synthesis reaction includes three consecutive steps and two reactions: first, a room-temperature CuBr-catalyzed synthesis of propargylamines, exo-yne-THIQs, from terminal alkynes, aldehydes, and THIQ, then filtration of the CuBr catalyst, and finally the ZnI2-mediated allene synthesis from the generated exo-yne-THIQs under mild conditions (either at room temperature or heating at 50 or 75 °C). A wide range of aliphatic or aromatic aldehydes and terminal alkynes are tolerated, affording the allene products in up to 92% yield. Especially, temperature-sensitive aldehydes can be used in the reaction system. Preliminary exploration of the asymmetric allene synthesis has also been conducted, and a moderate enantioselectivity has been achieved. Finally, the relative reactivities of several secondary amines were compared with THIQ, showing that THIQ is the best of these amines in the synthesis of allenes under mild reaction conditions.

DFT study on the mechanism and stereochemistry of the Petasis-Ferrier rearrangements.

The Petasis-Ferrier rearrangement is a very important and useful reaction for the synthesis of multifunctional tetrahydrofurans and tetrahydropyrans from easily synthesized enol acetals. Here we report our DFT investigation of the detailed reaction mechanism of the Petasis-Ferrier rearrangement, proposing that the active promoting species in this reaction is the cationic aluminum species, instead of the usually considered neutral Lewis acid (this will give very high activation energies and cannot explain why the Petasis-Ferrier rearrangements usually take place at low temperature or under mild conditions). Calculations indicated that the mechanisms of the Petasis-Ferrier rearrangements for the formations of five- and six-membered rings are different. Formation of five-membered tetrahydrofuranone is stepwise with C-O bond cleavage to generate an oxocarbenium enolate intermediate, which then undergoes an aldol-type reaction to give the desired cyclized oxacycle. In contrast, the formation of six-membered tetrahydropyranone is a concerted and asynchronous process with the C-O bond breakage and aldol-type C-C bond formation occurring simultaneously. A DFT understanding of why the catalytic versions of the Petasis-Ferrier rearrangements cannot be realized when using R2Al(+) as the active promoting species has also been discussed. In addition, DFT calculations were used to reveal the origins of the stereochemistry observed in the Petasis-Ferrier rearrangements.

Rh(I)-catalyzed [5+1] cycloaddition of vinylcyclopropanes and CO for the synthesis of α,ß- and ß,γ-cyclohexenones.

A cationic Rh(I)-catalyzed [5 + 1] cycloaddition of vinylcyclopropanes and CO has been developed, affording either ß,γ-cyclohexenones as major products or α,ß-cyclohexenones exclusively, under different reaction conditions.

Reaction of alpha-ene-vinylcyclopropanes: type II intramolecular [5+2] cycloaddition or [3+2] cycloaddition?

Exposure of alpha-ene-VCPs to catalytic [Rh(dppm)]SbF(6) led to the discovery of a novel Rh(I)-catalyzed [3+2] reaction, which was shown to be efficient for the construction of 5/6- and 5/7-bicyclic compounds rather than the anticipated type II [5+2] products.