A Highly Efficient Dimeric Manganese‐Catalyzed Selective Hydroarylation of Internal Alkynes

Abstract

We have developed a general and site‐predictable manganese‐catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio‐ and chemoselectivity originates from the unique reactivity of the manganese‐based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late‐stage modification of complex alkynes with precise regioselectivity.

Transition-Metal-Catalyzed Functionalization of Alkynes with Organoboron Reagents: New Trends, Mechanistic Insights, and Applications

“…The Xie group has recently expanded on this reactivity and devised a ligand-free manganese-catalyzed hydroarylation of tert-propargylic alcohols with boronic acids (Scheme 5b). 21 The reaction conditions are very user-friendly, tolerating the presence of water and an air atmosphere. Although the scope is limited to tertiary alcohols, the regioselectivity was complete, and the functional group compatibility was exceptionally high.…”

“…The Xie group has recently expanded on this reactivity and devised a ligand-free manganese-catalyzed hydroarylation of tert -propargylic alcohols with boronic acids (Scheme b) . The reaction conditions are very user-friendly, tolerating the presence of water and an air atmosphere.…”

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

“…Despite the wealth of reactivity that has been established in the catalytic functionalization of alkynes toward the construction of stereochemically defined olefins, 9 − 11 unsymmetrical dialkyl-substituted alkynes are noticeably absent from most contributions and, when present, typically provide unsatisfactory levels of reactivity and/or regioselectivity. 12 In an effort to enhance the involvement of this class of alkynes, our group has reported an indirect solution that relies on the use of a propargylic SO 2 Py directing group for achieving site-selectivity control. 13 In our previously reported Pd-catalyzed hydroarylation reaction, it was found that monodentate phosphine ligands significantly outperformed their bidentate analogues because they allow the alkyne substrate to accommodate through bidentate coordination in the ligand sphere of the metal, facilitating the regioselective insertion of the Pd–Ar σ-bond.…”

Manganese(I)‐Catalyzed Site‐Selective C6‐Alkenylation of 2‐Pyridones Using Alkynes via C−H Activation

“…[4] In this context, the manganesecatalyzed chelation-assisted alkenylation of (hetero) arene CÀ H bonds with alkynes has become the subject of increasing research attention in synthetic community. [4][5][6] In 2013, the Wang group first described the alkenylation of (hetero)arene CÀ H bonds with terminal alkynes using Mn(CO) 5 Br as the catalyst. [5a] Thereafter, terminal alkynes have been intensively explored in Mn-catalyzed (hetero)arene CÀ H bond alkenylation by the groups of Lei and Li, [5b] Wang, [5c,g] Ackermann, [5d] and others, [5e,f,h-j] and Mn(CO) 5 Br catalyst in combination with a base or acid additive or both worked well for these transformations.…”

“…In contrast, less success has been achieved with the more challenging internal alkynes, and only a handful of procedures are available. [6] 2-Pyridones are key structural units in numerous biologically active natural products and pharmaceuticals, [7] and also acts as valuable building blocks for the construction of important Nheterocycles. [8] As such, ever-growing research atten-tion has been focused on the development of efficient protocols for the synthesis of functionalized 2pyridones.…”