Stereodefined polymetalloid alkenes synthesis via stereoselective boron-masking of polyborylated alkenes

Abstract

Polyborylated-alkenes are valuable polymetalloid reagents in modern organic synthesis, providing access to a wide array of transformations, including the construction of multiple C–C and C–heteroatom bonds. However, because they contain similar boryl groups, many times their transformation faces the main challenge in controlling the chemo-, regio- and stereoselectivity. One way to overcome these limitations is by installing different boron groups that can provide an opportunity to tune their reactivity toward better chemo-, regio- and stereoselectivity. Yet, the preparation of polyborylated-alkenes containing different boryl groups has been rare. Herein we report concise, highly site-selective, and stereoselective boron-masking strategies of polyborylated alkenes. This is achieved by designed stereoselective trifluorination and MIDA-ation reactions of readily available starting polyborylated alkenes. Additionally, the trifluoroborylated-alkenes undergo a stereospecific interconversion to Bdan-alkenes. These transition-metal free reactions provide a general and efficient method for the conversion of polyborylated alkenes to access 1,1-di-, 1,2-di-, 1,1,2-tris-(borylated) alkenes containing BF3M, Bdan, and BMIDA, a family of compounds that currently lack efficient synthetic access. Moreover, tetraborylethene undergoes the metal-free MIDA-ation reaction to provide the mono BMIDA tetraboryl alkene selectively. The mixed polyborylalkenes are then demonstrated to be useful in selective C–C and C–heteroatom bond-forming reactions. Given its simplicity and versatility, these stereoselective boron-masking approaches hold great promise for organoboron synthesis and will result in more transformations.

Stereoselective Unsymmetrical 1,1‐Diborylation of Alkynes with a Neutral sp2−sp3 Diboron Reagent

“…This is probably attributed to the negligible differences in the nature of the two C−B(sp 2 ) groups in some thermodynamically and kinetically favoured transformations, such as the oxidation. To better differentiate the two boryl groups, Masarwa has very recently reported a boron‐masking approach to pre‐transfer the Bpin at the less steric hindered site of gem ‐di(Bpin)ethene to BMIDA (MIDA= N ‐methyliminodiacetic acid) before further functionalization (Scheme 2a) [13] . The synthesis of such 1,1‐Bpin‐BMIDA‐ethene has also been reported by Nishihara through a palladium‐catalyzed borylation of pre‐prepared ethynyl MIDA boronates [4j] …”

“…Both ‐Bpin and ‐BH 2 (NHC) moieties are introduced onto the terminal position of alkynes. In contrast to the boron‐masking strategy, which requires the pre‐preparation of 1,1‐di(Bpin)alkenes, followed by the introduction of the bulky ‐BMIDA group trans to the β‐substituents, [13] this method offers a one‐step synthesis from readily available substrates and enables the synthesis of E ‐selective UDBAs with the sp 3 boryl being cis to the β‐substituents on the olefin. Furthermore, according to the inertness of ‐BH 2 (NHC) toward oxidants, selective ‐Bpin oxidation gave acylboranes, whose synthesis is important but challenging.…”

“…To better differentiate the two boryl groups, Masarwa has very recently reported a boron-masking approach to pre-transfer the Bpin at the less steric hindered site of gem-di(Bpin)ethene to BMIDA (MIDA = N-methyliminodiacetic acid) before further functionalization (Scheme 2a). [13] The synthesis of such 1,1-Bpin-BMIDA-ethene has also been reported by Nishihara through a palladium-catalyzed borylation of preprepared ethynyl MIDA boronates. [4j] To circumvent the aforementioned restriction in the boron-differentiation and simplify the boron-masking strategy, a straightforward method and innovative borylation reagents are highly desired to direct equip the olefin with two chemically easily distinguishable boryl groups (Scheme 1b, right).…”

“…Compounds 5, obtained from the two-carbon homologation of UDBAs (R1F), were subsequently converted to substituted Z-stilbenes 13-15, through a one-pot process involving the treatment with N-chlorosuccinimide (NCS), hydrolysis and a palladium catalyzed Suzuki coupling with aryl iodides. [22] Both electron rich and deficient aryl iodides reacted well, leading to R2F products containing nitrile (13), ether (15), as well as amino acid valine ( 14) in 48 %-62 % yields (one purification, two steps from UDBAs) (Scheme 3d, condition A). It is noteworthy that the -Bpin group unexpectedly remained in the Z-stilbenes, after the Deprotonation of the terminal alkyne 2 a-D by potassium tert-butoxide produced the carbanion salt IM1 with the elimination of t BuOD.…”

Stereoselective Unsymmetrical 1,1‐Diborylation of Alkynes with a Neutral sp2−sp3 Diboron Reagent

“…Compounds 5, obtained from the two-carbon homologation of UDBAs (R1F), were subsequently converted to substituted Z-stilbenes 13-15, through a one-pot process involving the treatment with N-chlorosuccinimide (NCS), hydrolysis and a palladium catalyzed Suzuki coupling with aryl iodides. [22] Both electron rich and deficient aryl iodides reacted well, leading to R2F products containing nitrile (13), ether (15), as well as amino acid valine ( 14) in 48 %-62 % yields (one purification, two steps from UDBAs) (Scheme 3d, condition A). It is noteworthy that the -Bpin group unexpectedly remained in the Z-stilbenes, after the [a] Reaction conditions: reactions were conducted with 1 (0.05 mmol, 1.0 equiv), 2 a (0.075 mmol, 1.5 equiv) and base (0.01 mmol, 0.2 equiv) in solvent (0.5 mL) under nitrogen for 12 h. [b] Yields were determined by 1 Deprotonation of the terminal alkyne 2 a-D by potassium tert-butoxide produced the carbanion salt IM1 with the elimination of t BuOD.…”