JACS: Cu / PD catalytic reduction coupling of Alkynes

Alkynes, as a kind of easily available and versatile intermediate, have been widely used in organic synthesis Alkynes can take part in many reactions, the most common of which is the C-H functionalization of terminal alkynes, including addition to one π bond and double addition to two π bonds However, the differential transformation of two π bonds is still uncommon Only Buchwald group developed the first differential hydrogen functionalization reaction and applied it to the reductive hydrogen amination of alkynes (example 1) Recently, mankad group reported the method that alkynes were hydrogenated and then reduced to ketones (example 2) Recently, the Gojko lalic research group of Washington University reported a scheme 1b method of terminal alkyne differential dihydrofunctionalization Under the synergistic catalysis of copper and palladium, the end alkynes, arylhalides and pinacol borane were reduced coupled to form benzylalkyl borates Relevant articles were published on J am Chem SOC (DOI: 10.1021 / JACS 9b02372) (source: J am Chem SOC.) alkenyl bpin reported by sadighi research group was coppered to form heterobimetallic complexes (organometallics 2006, 25, 2405) and the inspiration of cupric hydride complex for hydrogenation functionalization of alkynes, the author tries to combine the above two reactions to develop a differential dihydrofunctionalization method for alkynes (scheme2) It is speculated that the copper catalyzed borohydride of alkynes and the hydrogen copperylation of alkenylborates (III) can form the intermediate IV of heterobimetallic compounds Under the catalysis of palladium, heterobimetallic intermediate (IV) and aryl bromide (II) are cross coupled to realize the differential dihydrofunctionalization of alkynes (source: J am Chem SOC.) to verify the above conjecture, the author used 5-phenyl-1-pentyne 1, 4-Bromoanisole 2 as raw materials, pinacol borane as coupling mate, iprcuo t-Bu and various metal palladium as catalyst to explore the reaction conditions (Table 1) After the selection of catalyst types and dosage, ligands, bases and concentrations, the author found that when iprcuo t-Bu and PD 2dba 3 were used as pre catalysts, xphos as ligands and Ko t-Bu as bases, in the presence of pinacol borane, 1 and 2 could react in toluene at 45 ℃ with 86% yield (source: J am Chem SOC.) after determining the optimal reaction conditions, the author investigated the application range of aryl bromide (Table 2) Both electron rich and electron deficient aryl bromides (3 - 18) are suitable coupling ligands, which are compatible with many functional groups, such as halogen, cyano, acetal, olefin, etc It is worth noting that a variety of heterocycles (19 - 23) containing o, N and s can also react smoothly Then, the author discussed the range of alkyne substrate Alkynes containing nitriles (25), epoxides (27), chlorides (29), bromides (30), acetals (35) and esters (36) are all compatible with the reaction system Even protected alcohols (28, 31 and 32) and alkynes (26, 40 and 41) substituted by functionalized phenylethers are suitable coupling mates Propargylic substituted alkynes (32 - 34) and several arylethynes (38, 39) were also obtained in good yields (source: J am Chem SOC.) based on mechanism experiments and related literature, the author proposed a reasonable reaction mechanism (scheme 5) At first, iprcuo t-Bu and hbpin were metallized to form iprcuh, which was coppered with terminal alkyne I to produce alkenyl copper VI The second equivalent hbpin and VI were metallized again to obtain alkenyl bpin III and to regenerate iprcuh Iprcuh was reinserted into III to obtain the heterobimetallic complex IV Subsequently, palladium catalyzed cross coupling of metal complex IV with aryl bromide resulted in different dihydrofunctionalized products V and Pd (0) (source: J am Chem SOC.) conclusion: the author developed a differential dihydrofunctionalization method for alkynes, which resulted in three-component reduction coupling of terminal alkynes, aryl bromide and pinacol borane Two regioselective hydrogenation functionalization of terminal alkynes catalyzed by copper / palladium can directly produce benzylalkylborate In addition, the reaction has excellent substrate range and functional group compatibility, and the product yield is high.