Catalytic asymmetric reactions with chiral titanium amide-alkoxide complexes Adam R. Johnson Department of Chemistry Harvey Mudd College, Claremont, CA 91711

Modular ligand synthesis 1 st generation, R’ = H 2 nd generation, R’ = alkyl

Ligand nomenclature 1 st generation 2 nd generation Can’t be made …

Initial hydroamination results 1 st generation ligands ee’s by chiral GC of benzamide derivative “blue” ee’s are opposite enantiomer (lower R f found with D -ligands) Organometallics, 2004, mol % cat., 110˚ C10 mol % cat., 135˚ C

Hydroamination with 2 nd generation ligands 2 nd generation ligands ee’s by chiral shift NMR using R -O-acetylmandelic acid “red” isomers (more downfield shift) correspond to same enantiomer as before (longer R f by GC) 5 mol % cat., 135˚ C Overnight reaction, >95% completion, single product

Benzaldehyde alkylation  -78° to room temperature overnight  Same reaction conditions for titanium complexes: 1.1 eq Et 2 Zn 5 mol% ligand 5 mol% Ti(O i Pr) 4

Alkylation data highlights  85-98% conversion; some reduction  R product favored with L -amino alcohols  Increase in %ee using Ti, but same enantiomer (in almost all cases)

Data

New directions  Sulfonamides  Tridentate ligands Electron withdrawing More rigidity

Sulfonamide ligands  Electron withdrawing ligands  Faster rate would allow for lower T and increase %ee Sulfonamide% conversion% ee% conversion% ee% conversion% ee A N/A B C1006no reaction D1004no reaction10N/A E1002no reactionnot performed F At 135 ˚CAt 110 ˚C At 95 ˚C

TiCl 2 (NMe 2 ) 2 starting material  Precipitates quantitatively (for 5a 92% isolated) and analytically pure from reaction mixture  insoluble Et 2 O, C 6 H 6, C 7 H 8 ; soluble in thf, CH 2 Cl 2  Complex 5b is more soluble, only 35% yield  Thermolysis gives new product/decomposition  1 H NMR spectrum incompatible with monomer Inorg. Chim. Acta, 2005, 358, 687

Low T Limit: 11 °C No change in spectrum down to -56 °C NHNH CH(CH 3 ) 2 NCH 3 CH(CH 3 ) 2

Dynamic NMR Behavior  Deuterated derivatives to simplify spectra  VT NMR used to determine first order rate constants  ∆H ‡ = kcal/mol  ∆S ‡ = 2-16 e.u. Proposed dynamic model

Acknowledgements  ACS-PRF, NSF-RUI, NSF-REU Undergraduate co-workers: Benzaldehyde alkylation: Casey M. Jones (Reed, ‘05), Hanhan Li (HMC, ‘05), Joanne E. Redford (HMC ‘09), Sam J. Sobelman (HMC ‘08), J. Andrew Kouzelos (HMC ‘07), Ryan J. Pakula (HMC ‘09) Hydroamination: Amanda J. Hickman (HMC ‘07), Lauren D. Hughs (HMC ‘09) New directions: Dianna C. McAnnally-Linz (Agnes Scott, ‘08), Katie E. Near (‘10), Minh T. Nguyen (U. La Verne, ‘08), Andrew H. Stewart (HMC, ‘08), Camille M. Sultana (HMC, ‘10)