Stereoselective Formation of Trisubstituted Vinyl Boronate Esters by the Acid-Mediated Elimination of α-Hydroxyboronate Esters

Abstract

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry.

α‐Hydroxyboronate Esters: Formation and Synthetic Applications

“…Considering the wealth of natural products and pharmaceutical compounds that contain trisubstituted alkenes, improved methods to access these synthetic intermediates with control of olefin stereochemistry is of considerable importance. Clark developed the synthesis of trisubstituted vinyl boronate esters by the acid‐catalyzed elimination of ketone diboration products (Scheme ) . Treatment of the unpurified diboration intermediates with p ‐toluenesulfonic acid (TsOH) at 65 °C provided the corresponding trisubstituted vinyl boronate esters 24 – 27 in moderate to high yields and generally good selectivity (Scheme ).…”

Vinylidenation of Organoboronic Esters Enabled by a Pd‐Catalyzed Metallate Shift

“…ing the palladium source from Pd(OAc) 2 to Pd 2 (dba) 3 gave slightly increased yields,but required catalyst loadings of 5% (see Supporting Information for details). With these modifications,3 -phenylpropyl (10)a nd n-octyl (11)m igrating groups were tolerated, as was asilyl ether (12). Ther eaction was also effective with cyclic substrates,including cyclopentyl (13), cyclohexyl (14), and N-Boc-protected piperidine (15) migrating groups.Migrating groups bearing potentially sensitive functional groups such as am onosubstituted olefin (16), amide (17), ester (18), or acetal (19)were also well-tolerated in this reaction.…”

“…Ther eaction was also effective with cyclic substrates,including cyclopentyl (13), cyclohexyl (14), and N-Boc-protected piperidine (15) migrating groups.Migrating groups bearing potentially sensitive functional groups such as am onosubstituted olefin (16), amide (17), ester (18), or acetal (19)were also well-tolerated in this reaction. While examples in Table 2s uggest that the reaction is effective with Grignard-derived "ate" complexes, it should be noted that alkyllithium derived "ate" complexes often offer superior reactivity such that catalyst loading can be reduced to 1mol %Pd, with many substrates still achieving complete conversion in one hour (10)(11)(12). Cyclic substrates (13 and 14), as well as at ertiary alkylboronic ester (20), required catalyst loadings of 5mol %for productive reaction.…”

“…This process thereby affords strategically-useful 1,1-disubstituted alkenylboronic esters by a catalytic vinylidenation of organoboronic ester precursors (Scheme 1). While a number of methods allow construction of similarly-substituted boron reagents, 10,11,12,13 the only direct conversion of an organoboron starting material to the vinylidenation product involves cross-coupling to (α-bromovinyl)-MIDA boronate (eq. 2) and this process is limited to C(sp 2 ) boronic acids as starting materials.…”

Facile Formation of β-Hydroxyboronate Esters by a Cu-Catalyzed Diboration/Matteson Homologation Sequence

“… 22 − 24 Subsequent studies have utilized these diboration products in the Suzuki–Miyaura coupling of trifluoroborate salts of the resulting α-hydroxyboronate esters 25 and in the formation of trisubstituted vinylboronate esters by acid-catalyzed elimination. 26 …”