Organoborons have emerged as versatile building blocks in organic synthesis to achieve molecular diversity and as carboxylic acid bioisosteres with broad applicability in drug discovery. ...Traditionally, these compounds are prepared by the substitution of Grignard/lithium reagents with electrophilic boron species and Brown hydroboration. Recent developments have provided new routes for the efficient preparation of organoborons by applying reactions using chemical feedstocks with leaving groups. As compared to the previous methods that used organic halides (I, Br, and Cl), the direct borylation of less reactive C–Het and C–C bonds has become highly important to get efficiency and functional-group compatibility. This Review aims to provide a comprehensive overview of this topic, including (1) C–F bond borylation, (2) C–O bond borylation, (3) C–S bond borylation, (4) C–N bond borylation, and (5) C–C bond borylation. Considerable attention is given to the strategies and mechanisms involved. We expect that this Review will inspire chemists to discover more efficient transformations to expand this field.
Conspectus The widespread presence of hydrocarbons makes C–H functionalization an attractive alternative to traditional cross-coupling methods. As indole is an important heteroarene in a plethora of ...natural products and pharmaceuticals, C–H functionalization of indole moieties has emerged as one of the most important topics in this field. Due to the presence of multiple C–H bonds in indoles, site selectivity is a long-standing challenge. Much effort has been devoted to the C–H functionalization of indoles at the C3 or C2 position, while accessing the benzene core (from C4 to C7) is considerably more challenging. This Account summarizes our recent efforts toward site-selective C–H functionalization of indoles at the benzene core based on innovative strategies. A common method to solve the issue involves the development of directing groups (DGs). Our early studies establish that the installation of the N-P(O) t Bu2 group at the N position can produce C7 and C6 arylation products using palladium and copper catalysts, respectively. The developed system can also be extended to direct arylation of indoles at the C5 and C4 positions by installing a pivaloyl group at the C3 position. Further investigation of indoles bearing N-P t Bu2 groups shows a more diverse reactivity for C–H functionalizations at the C7 position, including arylation, olefination, acylation, alkylation, silylation, and carbonylation with different coupling partners. Compared to the P(V) DG, the P(III) group can be easily attached to the indole substrates and detached from the products. However, these attractive reactions rely mostly on precious metal catalysts with ligands; this requirement can be a significant limitation, particularly for large-scale syntheses and the necessity of removal of toxic trace metals in pharmaceutical products. We have also uncovered a general strategy for chelation-assisted aromatic C–H borylation just using simple BBr3 under mild conditions, in which the installation of pivaloyl groups at the N1 or C3 position of indoles can selectively deliver the boron species to the unfavorable C7 or C4 positions and allow subsequent C–H borylation without any metal. This transition-metal-free strategy can be extended to synthesize C7 and C4 hydroxylated indoles by boron-mediated directed C–H hydroxylation under mild reaction conditions and with broad functional group compatibility. In this Account, we describe our contributions to this topic since 2015. These studies provide efficient and attractive methods for the divergent synthesis of valuable substituted indoles and insights into the exploration of new strategies for the site-selective C–H functionalization and directives for other important heteroarenes.
The first example of intermolecular olefination of cyclobutanone oximes with alkenes via selective C−C bond cleavage leading to the synthesis of nitriles in the presence of a cheap copper catalyst is ...reported. The procedure is distinguished by mild and safe reaction conditions that avoid ligand, oxidant, base, or toxic cyanide salt. A wide scope of cyclobutanones and olefin coupling components can be used without compromising efficiency and scalability. The alternative visible‐light‐driven photoredox process for this coupling reaction was also uncovered.
No construction without destruction: A copper‐catalyzed intermolecular olefination of cyclobutanone oximes with alkenes by C−C activation has been established. The method features mild and safe reaction conditions that avoid ligand, oxidant, base, or toxic cyanide salt, and a wide scope of cyclobutanones and olefin coupling components can be used without compromising efficiency and scalability.
The Rh-catalyzed, remote terminal hydroarylation of active olefins at the C7-position of indoles and the ortho-position of indolines and anilines with the appropriate choice of a N-P t Bu2 directing ...group through long-range deconjugative isomerization has been reported. This transformation not only overcomes the conjugate rule of Michael acceptors but also controls the positional selectivity of indoles, representing a significant advancement in both alkene isomerization and the C–H alkylation of indoles.
An efficient method for the metal‐free deaminative borylation of alkylamines, using bis(catecholato)diboron as the boron source, to directly synthesize various alkyl potassium trifluoroborate salts ...is introduced. The key to this high reactivity is the utilization of pyridinium salt activated alkylamines, with a catalytic amount of a bipyridine‐type Lewis base as a promoter. This transformation shows good functional‐group compatibility (e.g., it is unimpeded by the presence of a ketone, indole, internal alkene, or unactivated alkyl chloride) and can serve as a powerful synthetic tool for borylation of amine groups in complex compounds. Mechanistic experiments and computations suggest a mechanism in which the Lewis base activated B2cat2 unit intercepts an alkyl radical generated by single‐electron transfer (SET) from a boron‐based reductant.
N to B: A mild catalytic system was developed for the preparation of alkyl potassium trifluoroborate salts by C−N bond cleavage. This method has good functional‐group compatibility and can serve as a powerful synthetic tool for late‐stage borylative cleavage of C−N bonds in complex compounds. dtbpy=4,4′‐di‐tert‐butyl‐2,2′‐bipyridine.
For green and sustainable chemistry, molecular oxygen is considered as an ideal oxidant due to its natural, inexpensive, and environmentally friendly characteristics, and therefore offers attractive ...academic and industrial prospects. This critical review introduces the recent advances over the past 5 years in transition-metal catalyzed reactions using molecular oxygen as the oxidant. This review highlights the scope and limitations, as well as the mechanisms of these oxidation reactions (184 references).
Abstract
Sulfonium salts bearing a positively charged sulfur atom with three organic substituents have intrigued chemists for more than a century for their unusual structures and high chemical ...reactivity. These compounds are known to undergo facile single-electron reduction to emerge as a valuable and alternative source of aryl radicals for organic synthesis. However, the generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here we report the treatment of
S
-(alkyl) thianthrenium salts to generate non-stabilized alkyl radicals as key intermediates granting the controlled and selective outcome of the ensuing reactions under mild photoredox conditions. The value of these reagents has been demonstrated through the efficient construction of alkylboronates and other transformations, including heteroarylation, alkylation, alkenylation, and alkynylation. The developed method is practical, and provides the opportunity to convert C–OH bond to C–B and C–C bonds.
An effective and practical strategy has been established for the direct and site‐selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable ...pivaloyl directing group at the C3 position. This transformation shows good functional‐group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C−H bond without prefunctionalization of the reactive sites.
Grand Slam: An effective and practical strategy has been established for the direct site‐selective arylation of indoles at the C4 or C5 position (see scheme) by the use of a readily available and removable pivaloyl directing group (DG) at the indole C3 position. Now the direct site‐selective arylation of indoles at any given C−H bond is possible by the appropriate choice of this or a previously developed complementary method.
Transition metal-catalysed C-H hydroxylation is one of the most notable advances in synthetic chemistry during the past few decades and it has been widely employed in the preparation of alcohols and ...phenols. The site-selective hydroxylation of aromatic C-H bonds under mild conditions, especially in the context of substituted (hetero)arenes with diverse functional groups, remains a challenge. Here, we report a general and mild chelation-assisted C-H hydroxylation of (hetero)arenes mediated by boron species without the use of any transition metals. Diverse (hetero)arenes bearing amide directing groups can be utilized for ortho C-H hydroxylation under mild reaction conditions and with broad functional group compatibility. Additionally, this transition metal-free strategy can be extended to synthesize C7 and C4-hydroxylated indoles. By utilizing the present method, the formal synthesis of several phenol intermediates to bioactive molecules is demonstrated.
The nickel-catalyzed direct borylation and silylation of phenolic esters has been established. The key to this highly efficient acyl C–O bond borylative and silylative cleavage depends on the ...appropriate choice of different ligands and additives in the presence of nickel catalyst. Both transformations exhibit good functional group compatibility and can serve as powerful synthetic tools for late-stage functionalization of complex compounds. The elucidation of key mechanistic features of this newly developed acyl C–O bond activation in esters was confirmed by two well-characterized organonickel(II) intermediates.
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