1-[3,5-Bis(tert-butyl)phenyl]octahydro-3,6,6-trimethylcyclopenta[b]phosphole

Abstract

[232923-66-9] C24H39P (MW 358.54) InChI = 1S/C24H39P/c1-16-15-25(21-20(16)10-11-24(21,8)9)19-13-17(22(2,3)4)12-18(14-19)23(5,6)7/h12-14,16,20-21H,10-11,15H2,1-9H3/t16-,20+,21-,25+/m1/s1 InChIKey = LTXIQCIVTVZGOA-CAMXOCNWSA-N (reagent used as an asymmetric nucleophilic catalyst in kinetic resolution1 of alcohols) Alternate Name: ( + )-1-[3,5-bis(tert-butyl)phenyl]-octahydro-3,6,6-trimethylcyclopenta[b]phosphole, ( + )-(1R,2R,4S,5S)-4,8,8- trimethyl-2-(3′,5′-di-tert-butylphenyl)-2-phosphabicyclo[3.3.0]- octane (tBu2Ph-PBO). Physical Data: 2 ( + )-tBu2Ph-PBO/BH3 adduct 6: colorless crystals; mp 114–115 °C (MeOH/H2O); αD = + 15.1 (c, 3.2, EtOAc); 1H NMR (300 MHz, CDCl3) δ 7.65 (dd, J = 1.7, 11.5 Hz, 2H), 7.51 (q, J = 1.7 Hz, 1H), 2.62 (d, J = 10.2 Hz, 1H), 2.63–2.41 (m, 2H), 2.33–2.16 (m, 1H), 2.07–1.82 (m, 2H), 1.55–1.38 (m, 3H), 1.55–0.37 (br m, 3H), 1.33 (s, 18H), 1.21 (d, J = 6.3 Hz, 3H), 0.98 (s, 3H), 0.42 (s, 3H); 31P NMR (121.4 MHz, {H}, CDCl3) δ 33.3–30.5 (br m); IR (KBr, cm−1) 2361 (B-H); anal-ysis calculated: C, 77.39; H, 11.39, found: C, 77.27; H, 11.30. ( + )-tBu2Ph-PBO 1: obtained and used crude following heating the above borane adduct 6 in pyrrolidine at 50–55 °C for 90 min and evaporation of solvent under a stream of N2 to leave a colorless viscous oil (N.B. can be crystallized for analysis, see Purification below). αD = + 6.3 (c, 3.2, THF); 1H NMR (300 MHz, C6D6) δ 7.78 (dd, J = 1.8, 7.7 Hz, 2H), 7.45 (dt, J = 0.4, 1.8 Hz, 1H), 2.68 (dd, J = 9.9, 26.0 Hz, 1H), 2.52–2.34 (m, 2H), 2.25–2.11 (m, 1H), 1.95–1.81 (m, 1H), 1.75–1.56 (m, 1H), 1.46–1.22 (m, 3H), 1.30 (s, 18H), 1.07 (d, J = 6.3 Hz, 3H), 1.04 (s, 3H), 0.79 (s, 3H); 31P NMR (121.4 MHz, {H}, C6D6) δ -1.6; HRMS calculated for C24H39P: 358.2790, found 358.2786. Analysis of Reagent Purity: reagent purity is assessed for borane adduct 6. Enantiomeric excess is determined by conversion of cyclic sulfate 5 to the related Ph-PBO borane adduct and ee determined by CSP-HPLC; ee for tBu2Ph-PBO is assumed to be the same.2, 3 Isamagilov's mathematical treatment4 of the results of kinetic resolution (KR) reactions supports this assumption.2 Preparative Methods: 2 prepared as borane adduct 6 via an eight- step stereoselective synthesis from methyl (S)-lactate in an overall yield of 4.0% (eq 1). Borane adduct 6 is warmed with pyrrolidine to give the active catalyst ( + )-1 (>99.7% ee). The crude product, after removal of the solvent under a stream of N2, is then generally used directly. (1) Purification: the borane adduct can be crystallized from methanol/ water. Recrystallization of the active catalyst ( + )-1 is also possible from acetonitrile at −20 °C.3 Handling, Storage, and Precautions: no special precautions are taken to exclude oxygen from the KR reactions, although this does result in a 15–30% loss of catalyst due to phosphine oxide formation.3