A Modular Access to 1,2‐ and 1,3‐Disubstituted Cyclobutylboronic Esters by Consecutive Radical Additions

Abstract

A modular approach to substituted cyclobutylboronic esters is described. It proceeds by successive intermolecular radical additions of xanthates to pinacolato 1‐cyclobutenylboronate and to pinacolato bicyclo[1.1.0]but‐1‐ylboronate. Success hinges on tuning the stability of the α‐boryl radical by exploiting the stabilizing influence of the trivalent boronic ester and the slightly destabilizing cyclobutane, which increases the σ‐character of the radical. Reductive removal of the xanthate group finally provides a range of 1,2‐ and 1,3‐disubstituted cyclobutylboronic esters. The contrast with cyclopropylboronic esters is striking, since the strong destabilization by the highly strained cyclopropane ring allows the first radical addition to take place but not the second. Furthermore, the first adducts are geminal xanthyl boronic esters that can be converted into cyclobutanones. This chemistry furnishes cyclobutylboronic esters that would be quite difficult to obtain otherwise and thus complements existing methods.

Skeletal Ring Contractions via I(I)/I(III) Catalysis: Stereoselective Synthesis of cis-α,α-Difluorocyclopropanes

“…It is pertinent to note that exposing cyclobutene 2a directly to the reaction conditions led to rapid decomposition, rendering this approach impractical. 29 However, bicyclobutane reagents 30 proved to be compatible with the reaction conditions, and their propensity to rapidly isomerize to the corresponding cyclobutene under acidic conditions 22 rendered them ideally suited as masked reagents. When substrate 1a ( p -F-Ph) was exposed to 20 mol % of the catalyst in the presence of an amine·HF complex (ratio 1:5), it was possible to generate the desired product 3a (dr 9.0:1 cis : trans , Table 1 , entry 1), albeit with comparable quantities of the 1,4-diketone 4a (dr 18.0:1 cis : trans ).…”

Expanding the Chemical Space of 1,2-Difunctionalized Cyclobutanes

“…A vast majority of the reported methods not only do not aim at the synthesis of pure enantiomer but even provide diastereomeric mixtures. A number of recent publications provide exceptions to one or both of the above points; − important (and already classical) examples include stereoisomeric 2-aminocyclobutanecarboxylic acids prepared and used by the groups of Ortuño, ,− Aitken, − Bolm, and others as the building blocks for the synthesis of peptidomimetics and organocatalysts.…”

Photochemical [2+2] Cycloaddition of Alkynyl Boronates

“…Cyclobutane‐derived boronates and their preparation are broadly described in the literature [23–42] . On the contrary, the synthesis of cyclobutene‐derived boronates and their applications are very scarce.…”