Synthesis of a 9-Fluorenone Derived β-Amino Alcohol Ligand Depicting High Catalytic Activity and Pronounced Non-linear Stereochemical Effects

Abstract

The Jacobsen epoxidation of 9-alkylidenefluorenes 4a (ethylidene), 4b (benzylidene) and 4c (1-naphtylmethylene) with standard (R,R)-manganese salen catalyst has been studied. Both conversion and enantioselectivity depend on the steric bulk of the olefin substituent, best results being recorded with 4b (96% yield, 99% ee). The stereochemical course of the epoxidation of 4a is highly dependent on temperature and solvent, the ee of the resulting epoxide (S)-5a varying from 22% (-18°C, CH 2 Cl 2 ) to 49% (55°C, MTBE). The lithium perchlorate induced ring-opening of 5a with piperidine in MeCN affords a mixture of regioisomeric amino alcohols 3a/2a arising from the amine attack at the more substituted and less substituted carbons, respectively. The 3a/2a ratio can be modulated by the LiClO 4 concentration and the reaction temperature, and varies from 44:56 to 91:9. An independent, completely regiocontrolled synthesis of 3a has been developed involving ring-opening by the more substituted carbon of epoxide 5a with diisopropoxytitanium diazide, reduction of azidoalcohol 10a (H 2 , Pd/C) and cycloalkylation (1,5-dibromopentane, K 2 CO 3 ) of the amino alcohol 11a. The amino alcohol 3a exhibits a positive nonlinear stereochemical effect in its action as a ligand for the enantioselective addition of Et 2 Zn to benzaldehyde. The use of regiochemically pure 3a of >99% ee has been studied in the addition of Et 2 Zn to a representative family of aldehydes [19 examples, 93.6% mean ee]. The use of the directly available 9:1 mixture of 3a and 2a derived from 46-47% ee 5a as a ligand system for the enantioselective addition of Et 2 Zn to aldehydes [8 examples, 93.1% mean ee] is also reported.

Bond Angle Versus Torsional Deformation in an Overcrowded Alkene: 9-(2,2,2-Triphenylethylidene)fluorene

“…76.5–78.0 °C (lit. 103–104 °C,9b 52–54 °C9d); 1 H NMR 300 MHz, CHCl 3 , 25°C, TMS): δ =7.90 (d, 3 J (H,H)=7 Hz, 1 H; H11), 7.88 (d, 3 J (H,H)=7 Hz, 1 H; H2), 7.71 (d, 3 J (H,H)=8 Hz, 1 H; H8), 7.66 (d, 3 J (H,H)=8 Hz, 1 H; H5), 7.28–7.46 (m, 4 H; H3, H4, H9, H10), 6.88 (q, 3 J (H,H)=8 Hz, 1 H; CCH), 2.42 (d, 3 J (H,H)=7.7 Hz, 3 H; CH 3 ); 13 C NMR (75 MHz, CDCl 3 , 25 °C, TMS): δ =130.4, 127.9, 127.3, 124.9, 124.5, 112.8, 112.7, 112.4, 112.3, 110.4, 109.6, 105.3, 104.9, 104.6, 38.9; MS (70 eV): m / z (%): 192 (100). 1 H NMR peak assignments are numbered according to Figure 2…”

Recent Progress in Selective Additions of Organometal Reagents to Carbonyl Compounds

“…Pericàs et al reported the highly enantioselective ethylation of aliphatic aldehydes in the presence of 6 mol% of their devised chiral N,O-ligand 36 ( Table 9) [39]. The reactions proceed smoothly in 4 h under the mild conditions and almost quantitatively give the Et-adducts in 90-98% ee.…”

Catalyst-Dependent Direct and Deoxygenative Coupling of Alcohols by Convergent Paired Electrolysis

“…Specifically, selective azidation of diol (3a) gives an α-azido alcohol 12, and it could transform into α-amino alcohol via a facile hydrogenation. 63 Page 12 of 25 CCS Chemistry 13…”