Efficient Asymmetric Synthesis of a Bicyclic Amino Acid as a Core Structure of Telaprevir

Abstract

Telaprevir building block: Efficient asymmetric synthesis of bicyclic amino acid as a core structure of telaprevir has been accomplished via phase‐transfer catalyzed stereoselective conjugate addition of glycine derivative to cyclopent‐1‐enecarbaldehyde. This synthetic method can be applied to the asymmetric synthesis of 3‐substituted prolines.

α,β‐Unsaturated Aldehydes in the Synthesis of Five‐Membered Heterocyclic Compounds with One Heteroatom: Recent Advances from Developments in Metal‐ and Organocatalysis

“…In 2012, Maruoka et al . implemented an original three‐stage synthesis of chiral 3‐substituted prolines 87 , which starts from the asymmetric Michael addition of N‐ (diphenylmethylene)glycine esters 85 to 3‐propyl‐ or 3‐phenylpropenals in the presence of chiral phase‐transfer catalyst 86 (first in the pyrrolidine synthesis from enals).…”

Kinetic Resolution of Axially Chiral 2‐Amino‐1,1′‐Biaryls by Phase‐Transfer‐Catalyzed N‐Allylation

“…To achieve this important task, we have been interested in the chiral phase-transfer-catalyzed approach as shown in Scheme 1 d. [10] In the conventional N-acylation approach, the chiral catalyst, which is the activating acylation reagent, must recognize the chiral amino compounds from a remote place (Scheme 1 c). Attempted reactions of (AE)-1 a (X = SO 2 Ph) with allyl iodide (0.75 equiv) in aqueous KOH/toluene under the influence of catalysts of type (S)-3 [13] or (S,S)-4 [14] (2 mol %), which were some of the most reliable phase-transfer catalysts in our previous studies, [10] at 0 8C for 48 hours afforded the allylation product 2 a with low to moderate selectivities (s = 1.6-6.4, entries 1-4). Herein we report a valuable example of a highly selective kinetic resolution of axially chiral 2-amino-1,1'-biaryls by phase-transfer-catalyzed N-allylation.…”

Catalytic Asymmetric Synthesis of 3‐Substituted Proline Derivatives by Using Phase‐Transfer‐Catalyzed Conjugate Addition

“…This synthetic method can be applied to the efficient enantioselective synthesis of core structures in important biologically active compounds. [9] Results and Discussion…”

“…[15] To further expand the utility of the synthetic method, we are also interested in the asymmetric synthesis of bicyclic amino acid 6 as the core structure of telaprevir, which is a hepatitis C virus protease inhibitor (Scheme 5). [16] Although several examples of the preparation of bicyclic amino acid 6 in optically active form have been reported to date, [9,17,18] optical resolution or a stoichiometric amount of chiral reagent is required to obtain optically active product. For these reasons, the development of catalytic asymmetric methods for the efficient preparation of optically active bicyclic amino acid 6 is important task for synthetic organic chemistry.…”