Diversity-Oriented Approach to Cyclophanes via Fischer Indolization and Ring-Closing Metathesis: Substrate-Controlled Stereochemical Outcome in RCM

Abstract

Here, we report a new and diversity-oriented approach to macrocyclic cyclophanes by a Grignard reaction, followed by Fischer indolization and ring-closing metathesis (RCM) as key steps. The configuration of the double bond formed during the RCM depends upon the order of synthetic sequence used. Fischer indolization followed by RCM delivers the cis isomer, whereas RCM followed by Fischer indolization gives the trans isomer.

Design and Synthesis of Polycycles, Heterocycles, and Macrocycles via Strategic Utilization of Ring‐Closing Metathesis

“…Kotha and Chinnam reported an obvious route toward the synthesis of various benzoannulated propellanes such as 172 and 174 . The known dione 169 was prepared by cyclization of 2,3‐diphenylsuccinic acid using polyposphoric acid.…”

“…[20] In this context, synthesis of cyclophane derivatives containing both pyridine and indole systems has been described. [21] The synthesis of cyclophanes can be accom-plished by two different routes, which involves either the Fischer indolization (FI) followed by RCM protocol or alternatively the RCM followed by FI sequence. The required building block 66 was derived from commercially available starting material 65.…”

Design and Synthesis of Cyclic Mismatch‐Binding Ligands (CMBLs) with Variable Linkers by Ring‐Closing Metathesis and their Photophysical and DNA Repeat Binding Properties

“…[64,65] Notably, numerousn atural productsa nd several synthetic building blocks with variable ring size have been constructed through RCM reaction. [63][64][65][66][67][68][69] Few methods are availablet oc ontrol the stereochemicalo utcomeo ft he RCM process and al imited number of catalysts is available for this purpose. [63][64][65][66][67][68][69] Few methods are availablet oc ontrol the stereochemicalo utcomeo ft he RCM process and al imited number of catalysts is available for this purpose.…”

“…However,i ti ss till difficult to control the stereochemistry of the olefin during the macrocyclic formation in- www.chemeurj.org 2017 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim volvingR CM, and generally,i tg ives am ixture of cis and trans isomers. [63][64][65][66][67][68][69] Few methods are availablet oc ontrol the stereochemicalo utcomeo ft he RCM process and al imited number of catalysts is available for this purpose. [70][71][72] On the other hand, the mode of stacking, the relative orientation,a nd the distance between two chromophoric units would influence the electronic interaction and hence their photophysicalp roperties.…”

Microwave‐Assisted Rapid One‐Pot Synthesis of Fused and Non‐Fused Indoles and 5‐[18F]Fluoroindoles from Phenylazocarboxylates

“…Considering that the phenylazocarboxylates may beforehand be modified by mild nucleophilica romatic substitution, including the introductiono f[ 18 F]fluoride, the overall strategy offers an attractive new access to 5-[ 18 F]fluoroindoles.Indoles occur as structural elements in many pharmaceuticals, [1] natural products, [2] and compounds for diverse other applications. [3] Due to their importance,n ew synthetic methods are perpetually developed. [4] Recently published strategies comprise the assembly of the indole moiety through cobalt-, [5a-c] rhodium-, [5d,e] or palladium-catalyzed [5f-h] reactions of such diverse starting materials as nitrones, [5a] azo esters, [5d] hydrazides, [5c,e] nitrosoanilines, [5b] enamines, [5g] or imines.…”