Enantioselective Cu(I)-Catalyzed Cycloaddition of Prochiral Diazides with Terminal or 1-Iodoalkynes

Abstract

We report an unprecedented highly enantioselective desymmetric Cu­(I)-catalyzed 1,3-dipolar cycloaddition of diazides with terminal alkynes and 1-iodoalkynes, affording tertiary alcohols bearing a 1,2,3-triazole moiety in high yield and excellent ee value. PYBOX ligands with a C4 shielding group once again show the promising ability to achieve higher enantioselectivity.

Catalytic Enantioselective Construction of Chiroptical Boron-Stereogenic Compounds

“…In the presence of Cu­(CH 3 CN) 4 PF 6 (10 mol %) as the catalyst, BOX L1 – L3 (12 mol %) as the chiral ligands, and DABCO (1,4-diazabicyclo[2.2.2]­octane, 2.0 equiv) as the base in CHCl 3 at room temperature, the reaction between 1a with benzyl azide 2a successfully delivered the desired monocycloaddition product 3a , albeit in low yields with poor selectivities (Table , entries 1–3). In fact, the sense of the remote stereochemical information on the catalyst’s ligand environment and the overreaction toward undesired ditriazole are two severe problems in desymmetric CuAAC reactions. − To address these issues, bulky indane-fused BOX ligands L4 – L6 were tested in the transformation. The corresponding product 3a could be obtained in 24–64% yields with 41–54% ee (entries 4–6).…”

“…Herein, we report the exploration and realization of the first catalytic enantioselective construction of boron-stereogenic compounds via an asymmetric copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC) (Scheme c). Despite that the CuAAC reaction has been intensively studied and has found numerous applications in many areas of research, − asymmetric CuAAC is largely unexplored until recently. − In 2005, Fokin, Finn, and co-workers pioneered the study, proving the feasibility of enantioselective CuAAC via desymmetrization or kinetic resolution . In 2013, Zhou and co-workers developed a highly enantioselective CuAAC by desymmetrizing oxindolediynes, which allowed the successful construction of carbon stereogenic centers .…”

Chiral Tridentate-Based Ligands

“…Pybox are now well established and privileged ligands, regularly used to develop new catalytic systems. 14,15,16,17,18,19,20,21,22 23 Ruthenium complexes of Pybim were tested in the asymmetric epoxidation of olefins by hydrogen peroxide: the chemoselectivities in epoxide were from low to excellent with moderate enatioselectivities (epoxide ee up to 71% for t-stilbene with ligands from t-stilbenediamine (figure 5.2, left structure with R=1-naphtyloxy or (+)-menthyloxy). 23 Pybim ligands were also used in the zinc-catalyzed hydrosilylation of acetophenone, although with low enantioselectivities (ee = 16-24%).…”

“…In 1997, Zhang and coworkers described the synthesis of 3 new chiral NPN ligands 5. 16 (R 1 = Ph, R 2 = iPr, R 3 =H) and 5.17…”

“…The same team extended the use of ligands 5. 16 to the cobalt-catalyzed asymmetric allylic alkylation of carbon nucleophiles, in particular malonitriles (see Scheme 5.7 b)): good yields and very high enantioselectivities were obtained (yield = 61-96%; ee = 90-99% with 5.16 (R 1 = Me, R 2 = Me, R 3 = OMe)). 102 These ligands were also successfully used in the cobalt-catalyzed asymmetric allylic alkynylation of isatins (see Scheme 5.7 c)): yield = 71-96%; ee = 92-99% with 5.16 (R 1 = Ph, R 2 = Me, R 3 = H).…”