Stereocontrolled Synthesis of Chiral Helicene-Indenido ansa- and Half-Sandwich Metal Complexes and Their Use in Catalysis

Abstract

Despite recent tremendous progress in the synthesis of nonplanar chiral aromatics, and helicenes in particular, their conversion to half-sandwich or sandwich transition metal complexes still lags behind, although they represent an attractive family of modular and underexplored chiral architectures with a potential catalytic use. In this work, starting from various chiral helicene-indene proligands, we prepared the enantio- and diastereopure oxa[6]- and oxa[7]helicene-indenido half-sandwich Rh^I and Rh^III complexes and oxa[7]helicene-bisindenido ansa-metallocene Fe^II complex. To document their use, oxahelicene-indenido half-sandwich Rh^III complexes were employed as chiral catalysts in enantioselective C-H arylation of benzo[h]quinolines with 1-diazonaphthoquinones to afford a series of axially chiral biaryls in mostly good to high yields and in up to 96 : 4 er. Thus, we developed stereocontrolled synthesis of chiral helicene-indenido ansa- and half-sandwich metal complexes, successfully demonstrated the first use of such helicene Cp-related metal complexes in enantioselective catalysis, and described an unusual sequence of efficient central-to-helical-to-planar-to-axial chirality transfer.

Keywords: C−H activation; ansa-metallocene; enantioselective catalysis; half-sandwich complexes; helicenes.

Figure 1

A: Examples of chiral indenido half‐sandwich metal complexes used in enantioselective catalysis. B: Rare chiral helicene‐derived indenido, fluorenido and other sandwich metal complexes, not yet examined in catalysis. C: The chiral (oxa)helicene‐indenido half‐sandwich Rh^I (A) and Rh^III (B) complexes (structural variations marked in dark turquoise) and the ansa‐metallocene Fe^II complex 7 reported in this work were prepared enantio‐ and diastereopure; the Rh^III complexes were used in enantioselective C−H arylation with diazonaphthoquinones.

Scheme 1

Illustrative synthesis of enantio‐ and diastereopure helicene‐indene proligands (−)‐(M,R,R)‐14 a–e and (−)‐(M,R,R)‐18. Reaction conditions: (a) NIS (1.0 equiv.), DMF, 0 °C, 8.5 h, then AcCl (1.5 equiv.), Et₃N (2.5 equiv.), DCM, 0 °C to rt, 30 min, 60 %; (b) TIPS‐acetylene (3.0 equiv.), Pd(PPh₃)₂Cl₂ (5 mol %), CuI (10 mol %), Et₃N‐toluene (1 : 2), 40 °C, 3 h, 88 %; (c) K₂CO₃ (2.0 equiv.), MeOH, rt, 20 min, 97 %; (d) (−)‐(S)‐4‐(p‐tolyl)‐3‐butyl‐2‐ol 10 (1.2 equiv.), PPh₃ (1.1 equiv.), DIAD (1.2 equiv.), benzene, 0 °C to rt, 2 h, 94 %; (e) TBAF ⋅ 3H₂O (1.0 equiv.), THF, 0 °C, 5 min, 90 %; (f) 2‐iodophenol (3.0 equiv.), Pd(PPh₃)₄ (5 mol %), CuI (5 mol %), Et₃N (1.3 equiv.), toluene, 50 °C, 48 h, 70 %; (g) (−)‐(S)‐4‐(p‐tolyl)‐3‐butyl‐2‐ol 10 (1.2 equiv.), PPh₃ (1.1 equiv.), DIAD (1.2 equiv.), benzene, 0 °C to rt, 2 h, 84 %; (h) Ni(PPh₃)₂(CO)₂ (20 mol %), toluene, 120 °C, 5 min, 74 %; (i) MeMgBr (1.5 equiv.)/ EtMgBr (1.5 equiv.)/PhMgCl (2.0 equiv.)/o‐MeC₆H₄MgCl (1.5 equiv.)/p‐MeOC₆H₄MgBr (1.5 equiv.), THF, −80 °C to rt, 1 h, then p‐TsOH (20 mol %), toluene, 110 °C, 1 min, 88 % for 14 a, 72 % for 14 b, 85 % for 14 c, 66 % for 14 d, 83 % for 14 e; (j) THP‐protected 5‐hydroxy‐4‐iodo‐2,3‐dihydro‐1H‐inden‐1‐one 15 (2.0 equiv.), Pd(PPh₃)₄ (5 mol %), CuI (10 mol %), toluene‐Et₃N (3 : 1), 50 °C, 18 h, 79 %; (k) p‐TsOH (10 mol %), THF‐MeOH (1 : 1), rt, 18 h, 91 %; (l) (−)‐(S)‐4‐(p‐tolyl)‐3‐butyl‐2‐ol 10 (1.2 equiv.), PPh₃ (1.1 equiv.), DIAD (1.2 equiv.), benzene, 0 °C to rt, 4 h, 86 %; (m) CpCo(CO)(fum) (40 mol %), THF, flow reactor, 250 °C, 80 bar, 0.5 mL/min, 16 min residence time, 80 %; (n) NaBH₄ (8.0 equiv.), MeOH, rt, 30 min, then p‐TsOH (20 mol %), toluene, 110 °C, 1 min, 85 %.

Scheme 2

Preparation of the enantio‐ and diastereopure oxa[7]helicene‐bisindenido ansa‐ferrocene complex (M,R,R,S _p,S _p)‐7. Reaction conditions (in drybox): (a) KHMDS (2.0 equiv.), diethyl ether, rt, 5 min, 64 %; (b) FeCl₂ (1.0 equiv.), THF, −20 °C to rt, 18 h, 30 %.

Figure 2

ORTEP depiction of the XRD structure of (M,R,R,S _p,S _p)‐7 (CCDC 2373549). One pentane solvent molecule and hydrogen atoms are omitted for clarity, thermal ellipsoids are drawn at the 50 % probability level.

Figure 3

The optimized structure and relative energy of four possible diastereomers of the chiral oxa[6]helicene‐indenido Rh^I complex 22 a, calculated at the DFT B3LYP/Def2TZVP/GD3 level in vacuo using the Gaussian 16 package (hydrogen atoms omitted for clarity; grey: C, red: O, turquoise: Rh).

Figure 4

A part of the ¹H−¹H NOESY NMR spectrum of the enantio‐ and diastereopure Rh^I complex (−)‐(M,R,R,R _p)‐22 c showing a through‐space correlation between hydrogen atoms of the syn oriented pseudoaxial 7‐CH₃ group and the 1′‐CH unit of the coordinated COD‐Rh^I fragment. The molecular structure was optimized at the DFT B3LYP/Def2TZVP/GD3 level in vacuo using the Gaussian 16 package (only the concerned hydrogens shown; grey: C, red: O, turquoise: Rh, white: H).

Figure 5

Correlation of the ECD spectra of the enantio‐ and diastereopure oxa[6]helicene‐indene proligand (−)‐(M,R,R)‐14 a and the corresponding Rh^I and Rh^III complexes (−)‐(M,R,R,R _p)‐22 a and (−)‐(M,R,R,R _p)‐25a(Br), respectively, to demonstrate the conservation of M helicity of the scaffold; experimental spectra measured in THF (10⁻⁴ M); theoretical ECD spectra calculated at the TD‐DFT PBE0/Def2‐TZVP (or Def2‐SVP)/GD3/PCM (in THF) level using the Gaussian 16 package.

Scheme 3

Application of the enantio‐ and diastereopure oxa[6]helicene‐Indenido half‐sandwich Rh^III complex (−)‐(M,R,R,R _p)‐25 a(Br) in the model Rh^III‐catalyzed C−H activation associated with atroposelective [4+2] annulative coupling of biphenyl boronic acids with α‐diazo β‐ketoesters.