Rhodium‐Catalyzed Asymmetric Arylation of β,γ‐Unsaturated α‐Ketoamides for the Construction of Nonracemic γ,γ‐Diarylcarbonyl Compounds

Abstract

A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide.

Progress in the Chemistry of Tetrahydroquinolines

“…This reaction furnished γ,γ-diaryl ketoamide 965, which is a useful synthetic building block and was readily transformed into enantiomerically pure tetrahydroquinoline-2-carboxylamide 966 by reductive cyclization (Scheme 255). 414 Lautens and co-workers achieved a domino process giving access to enantioenriched tetrahydroquinolinone building blocks 970. 415 This transformation is initiated by a Rh-catalyzed conjugate arylation of an arylboronic acid 969 onto the unsaturated amide moiety in 968, followed by a Pd-catalyzed C−N cross-coupling process (Scheme 256).…”

Diverse Oxidative C(sp2)–N Bond Cleavages of Aromatic Fused Imidazoles for Synthesis of α-Ketoamides and N-(pyridin-2-yl)arylamides

“…With the optimized reaction conditions in hand, we next examined the reaction scopes for the diverse chemoselective aromatic C(sp 2 )−N bond cleavages in the preparation of both α-ketoamides 2 and N-(pyridin-2-yl)arylamide 3 (Table 2 to 4).…”

“…They could serve not only as promising human drug candidates but also as versatile starting materials in various synthetic transformations. 4 To date, numerous methodologies have been developed for the preparation of α-ketoamides and N-(pyridin-2-yl)arylamides from various substrates. 5 A variety of functional molecules, such as carboxylic acids, 5d nitriles, 5e halides, 5f,g alkynes, 5h alkenes, 5i aldehydes, 5j and ketones, 5k could be used as the amide precursors.…”

Rh-Catalyzed Highly Enantioselective Synthesis of Aliphatic Sulfonyl Fluorides

“…The Rh/binap catalyzed asymmetric addition of arylboronic acids to conjugated enones was firstly reported by Hayashi and Miyaura in 1998 (Takaya et al., 1998). This pioneering method has been rapidly developed in addition to various functional groups attached alkenes such as α,β -unsaturated esters (Duchemin and Cramer, 2019, Paquin et al., 2005a, Paquin et al., 2005b, Sakuma et al., 2000), amides (Yuan and Sigman, 2018, Wang et al., 2014, Hargrave et al., 2006, Sakuma and Miyaura, 2001, Senda et al., 2001), carbonyl (Bocknack et al., 2004, Kadam et al., 2017, Khiar et al., 2013, Moragues et al., 2015, Paquin et al., 2005a, Paquin et al., 2005b, Shintani et al., 2006, Yasukawa et al., 2015), phosphonates (Hayashi et al., 1999), imines (Cui et al., 2011, Jagt et al., 2006, Lee and Kim, 2015, Nishimura et al., 2012a, Nishimura et al., 2012b, Shintani et al., 2010, Trincado and Ellman, 2008, Wu et al., 2018), sulfonyl (Lim and Hayashi, 2015, Liu et al., 2019, Mauleon and Carretero, 2005, Nishimura et al., 2012a, Nishimura et al., 2012b, Takechi and Nishimura, 2015, Yan et al., 2019), nitro compounds (Wang et al., 2010, Hayashi et al., 2000, He et al., 2015, Miyamura et al., 2017), borylalkenes (Sasaki and Hayashi, 2010), and other electron-deficient alkenylarenes (Pattison et al., 2010, Saxena and Lam, 2011). We envision that through using Rh(I) catalyst and appropriate chiral ligand, the reaction of 2-arylethenesulfonyl fluorides with arylboronic acids would furnish a class of novel chiral molecules bearing both chiral gem-diarylmethane moiety and sulfonyl fluoride functionality (Scheme 1).…”