Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes

Abstract

Efficient methods for the convergent synthesis of (poly)cyclic scaffolds are urgently needed in synthetic and medicinal chemistry. Herein, we describe new annulation reactions of thioalkynes with phthalimide-substituted donor-acceptor cyclopropanes, which gave access to highly substituted cyclopentenes and polcyclic ring systems. With silyl-thioalkynes, Lewis acid catalysed (3+2) annulation reaction with DAcyclopropanes took place affording 1-thio-cyclopenten-3-amines. On the other hand, an unprecedented polycyclic compound was formed with alkyl-thioalkynes through a reaction pathway directly involving the phthalimide group. The two transformations proceeded in good yield and tolerated a large variety of functional groups.

A Brønsted Acid‐Catalyzed Michael Addition/Cyclization Sequence for the Diastereoselective Assembly of Chroman‐Bridged Polycyclic Isoindolinones

“…To test the feasibility of our synthetic design, initially, ethyl 3-carboxylate-substituted isoindolinone 1 a and ortho-hydroxychalcone 2 a were selected as model substrates. Delightfully, the expected cascade cyclization proceeded successfully under the catalysis of triflic acid, delivering the bridged polycyclic isoindolinone 3 a in 79% yield ( [8][9][10][11]. The competitive chromene-substituted isoindolinone was not detected in our system in all cases.…”

“…[7] However, these elegant approaches are mainly focused on the formation of fused polycyclic isoindolinones; in sharp contrast, the methods for the construction of bridged polycyclic isoindolinones have lagged far behind, and only two examples have been reported so far. [8] In 2014, Gautun's group reported a triflic acid-catalyzed Friedel-Crafts alkylation of phthalimide derivative to construct fused polycyclic isoindolinone in 21% yield, accompanied by the formation of bridged polycyclic isoindolinone in only 15% yield (Scheme 1a). [8a] Later, a Sc(OTf) 3 -catalyzed cascade annulation of thioal- 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 kynes with phthalimide-substituted donor-acceptor cyclopropanes was developed by J. Waser and coworkers, enabling the access to bridged isoindolinones in 60-78% yields (Scheme 1b).…”

Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

“…The [3+2] cycloaddition of silyl‐substituted thioalkynes 172 with phthalimide and aryl‐substituted DACs 3 provided a fast access to cyclopentene derivatives 173 in high yield (up to 96%) and regioselectivity (Scheme a). In contrast, alkyl‐substituted thioalkynes 172 underwent an unprecedented annulation with phthalimide‐substituted DACs 174 to afford new polycyclic ring systems 175 in good yields (60–78%) (Scheme b) …”

(3+3)‐Annulation of Carbonyl Ylides with Donor–Acceptor Cyclopropanes: Synergistic Dirhodium(II) and Lewis Acid Catalysis

“…[1] Besides alkenes and alkynes,w hich are the most prominent systems to undergo cycloaddition reactions,d onor-acceptor (D-A) cyclopropanes have in numerous cases been successfully involved in such transformations.T heir use as 1,3zwitterionic synthons is promoted by their high strain energy and by the polarized bond between the carbon atoms bearing the donor and the acceptor moiety.After seminal work in this field by Wenkert and Reissig some 30 to 40 years ago,the field has vastly expanded, especially during the last decade,leading to novel protocols of rearrangements,c ycloadditions,a nd ring-opening reactions. Most of the (1,n)dipoles that have been inserted are stable compounds (aldehydes, [4] imines, [5] allenes, [6] thiocarbonyls, [7] azides, [8] nitrones, [9] diaziridines;S cheme 1A [10] )o rc an be generated by the stoichiometric addition of base from astable precursor (such as nitrile imines;S cheme 1B). Most of the (1,n)dipoles that have been inserted are stable compounds (aldehydes, [4] imines, [5] allenes, [6] thiocarbonyls, [7] azides, [8] nitrones, [9] diaziridines;S cheme 1A [10] )o rc an be generated by the stoichiometric addition of base from astable precursor (such as nitrile imines;S cheme 1B).…”