Rhodium-Catalyzed Regiodivergent and Enantioselective Hydroboration of Enamides

Abstract

Chiral α- and β-aminoboronic acids exhibit unique biological activities. General methods for the synthesis of these bioisosteres of amino acids are highly desirable. We report a facile preparation of these compounds through rhodium-catalyzed regiodivergent and enantioselective hydroboration of enamides. Catalytic asymmetric synthesis of α- and β-aminoboronic esters with high regio-, diastereo-, and enantioselectivities were achieved through effective catalyst control and tuning substrate geometry. Starting from easily available materials, this strategy provides a unified synthetic access to both enantioenriched α-boration and β-boration products. The synthetic utility of these methods was demonstrated by efficient synthesis of an anticancer drug molecule and diverse transformations of the boration products.

Cu-Catalyzed Regio- and Stereodivergent Chemoselective sp/sp 1,3- and 1,4-Diborylations of CF3-Containing 1,3-Enynes

“…51 It is noteworthy that the homoallylic alcohols 2ag and 4ae obtained by our methods could not be accessed by known strategies or reported synthetic methods; therefore, our method provides a complementary strategy for the construction of CF 3 -containing homoallylic alcohols. 52,53 The alkenylation, thiophenation, and furanation of sp 3 Bpin moiety were also smoothly operated 54 (Figures 6B and 6B 0 ), the corresponding products were obtained in decent yields (2ah-2aj and 4af-4ah). Of note, compounds 2ah and 4af are valuable 1,5-dienes.…”

Catalytic Approach to Diverse α‐Aminoboronic Acid Derivatives by Iridium‐Catalyzed Hydrogenation of Trifluoroborate‐Iminiums

“…Recently, the challenge of α‐aminoboronic acid synthesis was tackled by reductive amination of acylboranes (Scheme 1, entries 1 and 2), [10,11] borylation of amides, [12–14] hydroboration of enamides, [15] electrophilic amination of gem ‐diborylalkanes (Scheme 1, entry 3), [16] a cascade copper‐catalyzed aminoboration of alkynes, [17] and also an interesting one‐pot borono‐Strecker reaction [18] . Two complementary rhodium‐catalyzed approaches were disclosed independently by two research groups, successfully hydrogenating α‐boryl enamides (Scheme 1, entry 4) [19,20] .…”

Synthesis and Applications of β‐Aminoalkylboronic Acid Derivatives

“…Very recently, Li and co‐workers realized a general method for the synthesis of monosubstituted and syn ‐α,β‐disubstituted β‐aminoalkylboronates by way of a Rh‐catalyzed hydroboration of enamides (Scheme 16). [53] When ( E )‐β‐substituted and ( E )‐α,β‐disubstituted enamide substrates were employed, the β‐hydroboration products, β‐aminoalkylboronates 21‐β , were formed selectively in moderate to excellent yields (Scheme 16). Surprisingly, by simply switching the geometry of the enamide substrate, under the same conditions the regioselectivity was reversed and favored the α‐hydroboration products, α‐aminoalkylboronates 21‐α (Scheme 16).…”