title: Sequential C-H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor.
abstract: A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C-H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl]2.
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Xudong
authors: X
authors: Wei
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Bo
authors: B
authors: Qu
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Xingzhong
authors: X
authors: Zeng
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Jolaine
authors: J
authors: Savoie
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Keith R
authors: KR
authors: Fandrick
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Jean-Nicolas
authors: JN
authors: Desrosiers
authors: Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors: Sergei
authors: S
authors: Tcyrulnikov
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Maurice A
authors: MA
authors: Marsini
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Frederic G
authors: FG
authors: Buono
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Zhibin
authors: Z
authors: Li
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Bing-Shiou
authors: BS
authors: Yang
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Wenjun
authors: W
authors: Tang
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Nizar
authors: N
authors: Haddad
authors: Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors: Osvaldo
authors: O
authors: Gutierrez
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Jun
authors: J
authors: Wang
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Heewon
authors: H
authors: Lee
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Shengli
authors: S
authors: Ma
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Scot
authors: S
authors: Campbell
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Jon C
authors: JC
authors: Lorenz
authors: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG , Birkendorfer Strasse 65, 88397 Biberach/Riss, Germany.
authors: Matthias
authors: M
authors: Eckhardt
authors: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG , Birkendorfer Strasse 65, 88397 Biberach/Riss, Germany.
authors: Frank
authors: F
authors: Himmelsbach
authors: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG , Birkendorfer Strasse 65, 88397 Biberach/Riss, Germany.
authors: Stefan
authors: S
authors: Peters
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Nitinchandra D
authors: ND
authors: Patel
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Zhulin
authors: Z
authors: Tan
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Nathan K
authors: NK
authors: Yee
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Jinhua J
authors: JJ
authors: Song
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Frank
authors: F
authors: Roschangar
authors: Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors: Marisa C
authors: MC
authors: Kozlowski
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors: Chris H
authors: CH
authors: Senanayake
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006865:Hydrogenation; D007495:Iridium / Q000737:chemistry; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D010880:Piperidines; D007495:Iridium; D010165:Palladium; C032727:piperidine; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1