Rhodium(II)‐Catalyzed Intramolecular Annulation of 1‐Sulfonyl‐1,2,3‐Triazoles with Pyrrole and Indole Rings: Facile Synthesis of N‐Bridgehead Azepine Skeletons

Abstract

A convenient and efficient synthetic method has been developed to construct highly functionalized N-bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular C-H functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.

Pd-Catalyzed Aerobic Oxidative Heck Cross-Coupling for the Straightforward Construction of Indole δ-Lactams

“…The efficient construction of the δ-lactam-containing (Figure 1, highlighted in red) ring-fused system has been the key issue of intensive synthetic efforts. The reported methods include free radical-induced cyclization (Magolan and Kerr, 2006, Magolan et al., 2008, Biechy and Zard, 2009, Zhu et al., 2015, Yu et al., 2016a, Yu et al., 2016b), Heck cross-coupling (Umehara et al., 2014, Iwama et al., 2013), and Friedel-Crafts reactions (Feng et al., 2015, Lv et al., 2014, Zhong et al., 2012, Zhong et al., 2014, Zhong et al., 2015, Liang et al., 2016, Zheng et al., 2018) at C 20 −C 21 ; the amidation of ester (Xu et al., 2013, Xu et al., 2015, Nakajima et al., 2010, Higuchi et al., 2015, Li et al., 2015) or oxidative amidation of alcohol (Pfaffenbach and Gaich, 2015) at N 1 −C 2 ; and the transannular cyclization (Yang et al., 2014a, Yang et al., 2014b, Dagoneau et al., 2016) of an aryl amide with ketone functionality via N 1 −C 21 .

Figure 1Selected Structures of Leuconoxine Subfamily

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“…To this end, we conceived of a transition-metal-catalyzed oxidative Heck coupling (i.e., dual dehydrogenative coupling) protocol, which, conceptually and strategically, would provide an ideal platform for accessing such structural skeletons as witnessed by the recent great advance in transition-metal-catalyzed oxidative C‒C bonding formation (Shi et al., 2011, Liu et al., 2011, Liu et al., 2015). In fact, there has been rapidly growing interest in oxidative Heck-type coupling of indole and other classes of substrates (Abbiati et al., 2003, Ferreira and Stoltz, 2003, Ferreira et al., 2008, Schiffner et al., 2010, Pintori and Greaney, 2011, Kandukuri et al., 2012, Kandukuri and Oestreich, 2012, Broggini et al., 2012, Yang et al., 2014a, Yang et al., 2014b, Ikemoto et al., 2014, Gao et al., 2016, Meng et al., 2013, Meng et al., 2014), and the great advantage of the related reaction in natural product synthesis has been demonstrated early by the synthesis of a few indole-type natural products (Baran et al., 2003, Meng et al., 2015, Lu et al., 2014).…”

Catalytic Insertion Reactions of α‐Imino Carbenoids

“…derivatives 68 was accomplished by Shi and co-workers in 2014 (Scheme 15a). [31] A variety of N-tethered pyrrolyl or indolyl triazoles 65 were synthesized and when treated with Rh 2 (Oct) 4 in dry 1,2-DCE at 80 °C, the resultant imino carbene intermediates underwent facile C2À H insertion to generate 67, which upon one-pot reduction with NaCNBH 3 delivered the pyrrole or indole fused azapine scaffolds 68 in moderate to good yields. To showcase the synthetic application of this protocol, further transformations of 68 were carried out for the construction of polycyclic azepines.…”

Reactions of metallocarbenes derived from N-sulfonyl-1,2,3-triazoles

“…52 Tang and Shi have reported the intramolecular annulation of pyrrolyl and indolyl triazoles to provide azepine derivatives. 53 Tang described an alternative entry into azepines by a tandem cyclopropanation/aza-Cope rearrangement. 54 Anbarasan reported the direct arylation of the imino carbenes to form diarylenamides.…”