Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition

Abstract

An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst.

Highly Enantioselective Catalytic Vinylogous Propargylation of Coumarins Yields a Class of Autophagy Inhibitors

“…[1] Based on this principle we developed biologyoriented synthesis (BIOS) as aguiding principle for the design and synthesis of compound collections enriched in diverse bioactivities. [3] Therefore,t he development of enantioselective methods to access diverse NP-inspired compound collections rapidly and efficiently is highly desirable. [3] Therefore,t he development of enantioselective methods to access diverse NP-inspired compound collections rapidly and efficiently is highly desirable.…”

Diastereodivergent Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides and β‐Fluoroalkyl Vinylsulfones: Low Copper(II) Catalyst Loading and Theoretical Studies

“…[2] The 1,3-dipolar cycloaddition of azomethine ylides [3] and activated alkenes represents as traightforward, powerful, and highly atom-economic solution to install pyrrolidine frameworks with up to four adjacent stereogenic centers.During the past two decades,t he exploration of novel catalytic asymmetric 1,3-dipolar cycloadditions with functionalized alkenes [for example,C ( =O)R, NO 2 ,S O 2 Ph, CN,P ( =O)(OR) 2 )] as dipolarophiles has drawn great attention. [5] Despite these tremendous advances,t he known synthetic methods still suffer from various problems,such as:1)high catalyst loading (at least 5mol %);2 )rarely using cheaper and more stable Cu II catalysts in contrast to Cu I catalysts; [6] 3) few examples of providing exo'-adducts as the major isomers; [7] 4) limited trifluomethylated starting materials. [5] Despite these tremendous advances,t he known synthetic methods still suffer from various problems,such as:1)high catalyst loading (at least 5mol %);2 )rarely using cheaper and more stable Cu II catalysts in contrast to Cu I catalysts; [6] 3) few examples of providing exo'-adducts as the major isomers; [7] 4) limited trifluomethylated starting materials.…”

Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis

“…Herein, we report the first enantioselective biologyoriented synthesis [7,8] of the spirotropanyl oxindole scaffold by means of ab imetallic relay catalysis strategy employing ahighly enantioselective 1,3-dipolar cycloaddition as the key step (Scheme 1c). In this strategy,t he azomethine ylides are generated from E-oximino a-diazo ketones 1 by intramolecular Rh II carbenoid transfer to the oxime.I nt he subsequent 1,3-dipolar cycloaddition, enantioselectivity is efficiently induced by the interaction between 3-alkenyl oxindoles 2 and aL ewis acid complex comprised of Nd III and ac hiral N,N'-dioxide ligand.…”

“…This finding is in agreement with previous reports that azomethine ylides generated by carbenoid transfer to imines do not strongly coordinate to Rh II catalysts. [14] However, neither the magnesium salt of chiral phosphate 6a [15] (Table 1, entry 3) nor the complex formed from BOXl igand 6b (and other BOXligands;data not shown) with Mg(NTf 2 ) 2 (Table 1, entry 4) [16] gave satisfying results.F inally,t he N,N'-dioxide ligands developed by Feng et al were tested (Table 5, entries [5][6][7][8][9]. [14] However, neither the magnesium salt of chiral phosphate 6a [15] (Table 1, entry 3) nor the complex formed from BOXl igand 6b (and other BOXligands;data not shown) with Mg(NTf 2 ) 2 (Table 1, entry 4) [16] gave satisfying results.F inally,t he N,N'-dioxide ligands developed by Feng et al were tested (Table 5, entries [5][6][7][8][9].…”