Synthesis of Bicyclic and Tricyclic Chiral Guanidinium Salts by an Intramolecular Alkylation Approach

Abstract

Synthetic studies leading to three new types of chiral guanidinium scaffolds are described. Structures of interest include bicyclic guanidine derivatives with various substitution patterns around the guanidine core, as well as a highly rigid tricyclic scaffold. The challenging targets were accessed by application of mercury(II)‐promoted guanylation of N‐Boc‐substituted thioureas and Ishikawa's desulfurative cyclization. In addition to our synthetic logics, a scalable synthesis of the tricyclic guanidinium salt is presented.

Facile conversion of 1,2-dicyanobenzene into chiral bisamidines

“…Chiral amidines and guanidines are versatile compounds that have been applied many times in studies on molecular recognition [1][2][3][4][5][6] and enantioselective catalysis. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Our group, for example, has introduced the bisamidines 1 and 2 (Figure 1). 25,26 In the protonated state, these compounds promote Diels-Alder reactions as electrophilic catalysts.…”

Synthesis of sp3-rich heterocyclic frameworks by a divergent synthesis strategy

“…Another [5,6,6]-tricyclic fragment (8) was accomplished by an intramolecular [4 + 2] cycloaddition between acylnitroso 16 and diene in an inseparable 1 : 2 diastereomeric mixture. 17 Next, the focus was turned to bicyclic fragments by the formation of 9 from an allenamide cycloisomerisation reaction between an alkyne and 2°amide. The use of nitro alkenes was revisited as they are readily available and can introduce a large range of synthetic handles and modulate physicochemical properties, here showcased by trans-β-nitrostyrene.…”