Anion-Mediated, Stereospecific Synthesis of Secondary and Tertiary Cyclopropylboronates from Chiral Epoxides and gem-Diborylalkanes

Abstract

We report a transition-metal-free deborylative cyclization approach to synthesize enantioenriched secondary and tertiary cyclopropylboronates using γ-phosphate-containing gem-diborylalkanes derived from chiral epoxides and gem-diborylalkanes. Our method enables the synthesis of a broad range of enantioenriched secondary and tertiary cyclopropylboronates in good yields with excellent stereospecificity. We demonstrate the versatility of our approach by performing a gram-scale reaction. We also show that the enantioenriched tertiary cyclopropylboronates can be transformed into a wide array of enantioenriched cyclopropane derivatives in a stereospecific boron-group transformation.

Photogeneration of α-Bimetalloid Radicals via Selective Activation of Multifunctional C1 Units

“…Control reactions highlight that both additive and light are required for efficient reactivity (entries 10 and 11). It is pertinent to note in both control reactions close to full recovery of substrate 1a was achieved, indicating that both light and Lewis base are required for efficient activation of the C–I bond and that the developed method is orthogonal to ground-state reactivity previously established in the literature (Figure c). − …”

“…Classic solutions to overcome this obstacle include deprotonation and harnessing reactive organometallics to generate α-bimetalloid anion synthetic equivalents (Figure C) . These reactive intermediates are still frequently employed and have been leveraged in elegant strategies for mono- or chemoselective activation (M = Li, B, Si) enabling efficient reactivity with various electrophiles, and application in transition metal-catalyzed cross-coupling . The recent emergence of trivalent ambiphilic C1 units that contain at least one pendant C–X bond has enabled extension to α-bimetalloid electrophile synthetic equivalents (Figure C), where selective engagement of the C–X bond is achieved via exposure to nucleophilic species such as amines, and organometallics. , However, while closed shell reactivity has been comparatively well established and continues to expand, synthetic tools that enable the efficient generation of an α-bimetalloid radical are conspicuously underexplored, yet desirable given their orthogonal reactivity to closed shell paradigms.…”

Silver-catalyzed direct conversion of epoxides into cyclopropanes using N-triftosylhydrazones

“…Recently, the Hong and Cho groups independently synthesized enantioenriched cyclopropylboronates via a two-step three-component reaction of chiral epoxides with lithiated gem -diboronates and diphenyl chlorophosphate (Fig. 1a 3 ) 31 , 32 . Noyori realized the only example of an oxygen-carbon exchange reaction by heating with ethyl diazoacetate at 130–140 °C, where small amounts of competing C–O and C–H insertion products were also formed (Fig.…”

Synthesis of Borylated (Aminomethyl)cyclopropanes Using C1–Bisnucleophiles

“…Oxygen-based electrophiles have emerged as a privileged class of reagents, with early reports showing that esters can be trapped with lithiated 1,1-diborylalkanes to form ketones (Scheme a) . More recently, the use of ketones/aldehydes (Boron-Wittig) and epoxides (ring-opening) , has received significant attention for the synthesis of borylated alkenes and β-boryl alcohols, respectively. Reactions with epoxides are noteworthy, as the alkoxide formed upon ring opening can act as a Lewis base and activate one of the boronic esters in an intramolecular fashion.…”