Copper(I)-Catalyzed Enantioselective Borylative Dearomatization of Indoles
The first enantioselective borylative dearomatization of a heteroaromatic compound has been achieved using a copper(I) catalyst and a diboron reagent. This reaction involves the unprecedented regio- and enantioselective addition of borylcopper(I) active s
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Copper(I)-Catalyzed Enantioselective Borylative Dearomatization of Indoles
Abstract The first enantioselective borylative dearomatization of a heteroaromatic compound has been achieved using a copper(I) catalyst and a diboron reagent. This reaction involves the unprecedented regio- and enantioselective addition of borylcopper(I) active species to indole-2-carboxylates, followed by the diastereoselective protonation of the resulting copper(I) enolate to give the corresponding chiral indolines bearing consecutive stereogenic centers.
7.1
Introduction
Aromatic compounds are ubiquitous in nature and readily available as synthetic materials. The enantioselective dearomatization reactions of heteroaromatic compounds are very powerful transformations because they can be used to provide direct access to a wide variety of chiral-saturated heterocycles, which are important components of pharmaceutical drugs and bioactive molecules [1–3]. The development of new methods for the formation of consecutive stereogenic centers via the stereoselective dearomatization of multi-substituted aromatic compounds would also have important practical implications for the synthesis of natural products [4]. Enantioenriched organoboron compounds are recognized as useful chiral building blocks in synthetic chemistry because they can be readily applied to the stereospecific functionalization of stereogenic C–B bonds [5–7]. Considerable research efforts have recently been devoted to the development of new methods for the metal-catalyzed enantioselective hydro- and protoboration reactions of prochiral C=C double bonds [8–12]. Despite significant progress in this area, there have been no reports pertaining to the development of C–B bond-forming dearomatization reactions. The lack of research in this area is most likely caused by the high energy barrier encountered during the dearomatization process [1–3]. The development of an enantioselective C–B bond-forming dearomatization reaction would provide an
© Springer Nature Singapore Pte Ltd. 2017 K. Kubota, Synthesis of Functionalized Organoboron Compounds Through Copper(I) Catalysis, Springer Theses, DOI 10.1007/978-981-10-4935-4_7
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Copper(I)-Catalyzed Enantioselective Borylative Dearomatization …
O R1
N 1 R3 + O O B B O O 2
OR 2 cat. Cu(I)/L*
O O
B O
R 4OH
B O H O
OCuL
base N R3
OR 2
R1
N OR 2 R3 3 up to 98% yield up to 97% ee up to 97:3 d.r.
Scheme 7.1 Copper(I)-catalyzed enantioselective C–B bond-forming dearomatization of indoles
attractive and complementary approach for the synthesis of complex, functionalized cyclic molecules in combination with the stereospecific transformation of a stereogenic C–B bond. Ohmura et al. [13] and Weetman et al. [14] independently reported the results of their pioneering studies toward the development of a borylative dearomatization reaction, where pyridines were subjected to a dearomative hydroboration reaction with pinacolborane in the presence of Rh(I) and Mg(II) catalysts. In 2014, Marks et al. [15] reported the development of a simi
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