Synthesis and Enantioselectivity of P‐Chiral Phosphine Ligands with Alkynyl Groups

Abstract

General.All solvents used in reactions were dried and purified according to standard procedure. NMR spectra were measured with JEOL JMN-GXS-500 (500 MHz) or JEOR JMN-LA-400 (400 MHz) spectrometer in CDCl 3 . Chemical shifts were reported in δ ppm. Optical rotationswere measured with JASCO DIP-370 polarimeter. Enantiomeric excesses were determined by HPLC analysis using Chiralcel AD, OJ-H, OD-H, OB, IA columns and varying concentrations of 2-propanol/hexane as the mobile phase. X-ray crystal structure data were collected using a Bruker SMART APEX II diffractmeter with Mo-Kα radiation. Silica gel (Kanto Chemical, Silica Gel 60N for flash chromatography) was used for column chromatography. (S)-tert-Butylmethyl(phenylethynyl)phosphine-borane (3a)To a solution of (S)-tert-butylmethylphosphine-borane (1) (>99% ee, 1.8 g, 15.4 mmol) in dry Et 2 O (60 mL) was added nBuLi (11.6 mL of a 1.60 M solution in hexane, 18.5 mmol) at -78 °C under nitrogen, and the mixture was stirred for 15 min. 1,2-Dibromoethane (2.0 mL, 23.1 mmol) was added dropwise, and the reaction mixture was stirred at -78 °C. After 2 h, lithium phenylacetylide (30.8 mmol, 30 mL of Et 2 O solution) was added to the reaction mixture, and the mixture was stirred at room temperature. After 1.5 h, the reaction was quenched with 1 M HCl. The mixture was extracted with EtOAc three times. The combined organic layers were washed with saturated NaHCO 3 and brine, and dried over Na 2 SO 4 . After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by chromatography on silica gel (hexane/EtOAc = 5/1) to give (S)-tert-butylmethyl(phenylethynyl)phosphine-borane (3a) (97% ee, 2.8 g, 12.8 mmol, 83%) as white solid.

Enantioselective Synthesis of P‐Stereogenic Alkynylphosphine Oxides by Rh‐Catalyzed [2+2+2] Cycloaddition

“…Several research groups reported the efficient asymmetric synthesis of P‐stereogenic phosphorus compounds12 by resolution13 (including dynamic resolution13a–c), desymmetrization,14 and catalytic asymmetric reactions 15. Recently, Imamoto et al demonstrated that P‐stereogenic phosphine ligands bearing alkynyl groups induced excellent enantioselectivity in various transition‐metal‐catalyzed asymmetric reactions 16. We anticipated that if selective mono [2+2+2] cycloaddition of symmetrical dialkynylphosphine oxides with 1,6‐diynes proceeds by using cationic rhodium(I) complexes with modified 2,2’‐bis(diphenylphosphanyl)‐1,1’‐binaphthyl (binap) ligands as a catalyst, then P‐stereogenic alkynylphosphine oxides could be accessed by desymmetrization (Scheme ) 17…”

Stoichiometric and Catalytic Synthesis of Alkynylphosphines

“…The single example relating the synthesis of a set of enantiopure P-stereogenic alkynylphosphines was described by Imamoto [ 5 ] ( Scheme 8 ). The procedure relies on the in situ generation of a P-stereogenic bromophosphine-borane from an enantiopure secondary phosphine-borane via deprotonation by n -butyllithium in diethyl ether at −78 °C and subsequent halogenation of the resulting lithium phosphido-borane by treatment with dibromoethane.…”

“…The Imamoto group [ 5 ] described a 4-step reaction sequence allowing the synthesis of an alkynyl variant of BisP* ligands, analogous to DIPAMP [ 27 ], from an enantiopure silyl alkynylphosphine-borane ( Scheme 18 ). The first step was a dimerization reaction through copper(II)-catalyzed oxidative coupling leading to the bis-alkynylphosphine-borane 2 .…”

“…It is only recently that the high potential of alkynylphosphines as ligands for homogeneous catalysis has emerged through a few relevant catalytic applications [ 4 ]. Notably P-stereogenic alkynylphosphines were shown to induce excellent enantioselectivity in several asymmetric transition metal-catalyzed reactions [ 5 ]. Moreover the easy transformation of alkynylphosphines into valuable functionalized alkenyl mono- or di-phosphines through addition reactions on the triple bond was recently demonstrated [ 6 ].…”

Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles

“…In addition to rhodium catalysts, other transition metal catalysts may be used for asymmetric ring-opening reactions of oxabicyclic alkenes. These include complexes of copper [ 20 – 25 ], palladium [ 14 – 15 26 – 31 ], iron [ 32 ], and nickel [ 33 – 36 ]. Recently, we reported for the first time iridium-catalyzed asymmetric ring-opening of N -Boc-azabenzonorbornadiene with a wide range of secondary amines [ 37 ].…”