Organocatalytic Asymmetric Synthesis of Si-Stereogenic Silyl Ethers

Abstract

Functionalized enantiopure organosilanes are important building blocks with applications in various fields of chemistry; nevertheless, asymmetric synthetic methods for their preparation are rare. Here we report the first organocatalytic enantioselective synthesis of tertiary silyl ethers possessing “central chirality” on silicon. The reaction proceeds via a desymmetrizing carbon–carbon bond forming silicon–hydrogen exchange reaction of symmetrical bis(methallyl)silanes with phenols using newly developed imidodiphosphorimidate (IDPi) catalysts. A variety of enantiopure silyl ethers was obtained in high yields with good chemo- and enantioselectivities and could be readily derivatized to several useful chiral silicon compounds, leveraging the olefin functionality and the leaving group nature of the phenoxy substituent.

Imidodiphosphorimidates (IDPis): Catalyst Motifs with Unprecedented Reactivity and Selectivity

“…After the successful endeavors in deriving chiral silyl enol ethers through Si‐H exchange reactions, the List's team recently reported on the first organo‐acid‐catalyzed enantioselective synthesis of Si‐stereogenic tertiary silyl ethers 50 via desymmetrizing, carbon‐carbon bond forming silicon‐hydrogen exchange reaction of symmetrical bis(methallyl)silanes 48 with phenol 49 (Scheme 7). [ 54 ] After the olefin protonation by IDPi catalyst, intramolecular cation‐π cyclization and Si—C bond cleavage occurs sequentially on the β ‐silyl‐stabilized cation I , leading to silylium ion pair III in readiness for nucleophilic attack. IDPi C3 or C4 catalyzes the formation of various benzyl‐ and (hetero)aryl‐substituted chiral silanes 50 in high yields and good er.…”

N-Heterocyclic Carbene-Catalyzed Desymmetrization of Siladials To Access Silicon-Stereogenic Organosilanes

“…(S)-2-((2-Formylphenyl)(methyl)(phenyl)silyl)benzoic acid (6). Following the above procedure, 3aa (87.3 mg, 0.2 mmol) was reacted with NaOH (80.0 mg, 2.0 mmol) to give 6 as a white solid, 55.2 mg, 80% yield, mp 162−164 °C, obtained by purification with flash column chromatography on silica gel using petroleum ether/ EtOAc (v/v) = 5/1 as the eluent.…”

“…Over the past two decades, transition-metal-catalyzed desymmetrization of prochiral dihydrosilanes or tetraorganosilanes has received significant attention and been extensively explored . Very recently, the List group reported a chiral imidodiphosphorimidate-mediated desymmetrization of bis­(methallyl)­silanes to furnish silicon-stereogenic silyl ethers (Scheme a) . During the preparation of this manuscript, Zheng, Chi, and co-workers described a chiral triazolium salt-triggered desymmetrization of silicon-centered dialdehydes to provide silicon-stereogenic silanes (Scheme b) .…”

“…5 Very recently, the List group reported a chiral imidodiphosphorimidate-mediated desymmetrization of bis(methallyl)silanes to furnish silicon-stereogenic silyl ethers (Scheme 1a). 6 During the preparation of this manuscript, Zheng, Chi, and co-workers described a chiral triazolium salt-triggered desymmetrization of silicon-centered dialdehydes to provide silicon-stereogenic silanes (Scheme 1b). 7 Nevertheless, creation of an optically pure silicon center in an organocatalytic manner is still in its infancy.…”

A Silicon‐Stereogenic Silanol ‐18O‐Isotope Labeling and Stereogenic Probe Reveals Hidden Stereospecific Water Exchange Reaction

“…[15][16][17] However, the preparation of Si-chiral compounds has proven challenging in the past due to limited access to suitable prochiral or chiral precursors. [18][19][20][21][22][23][24][25] Combined with the metastability of silanols, which can lead to undesirable selfcondensation processes to siloxanes, this creates a major synthetic hurdle. Therefore, the synthetic access is challenging.…”