Ring‐Opening Regio‐, Diastereo‐, and Enantioselective 1,3‐Chlorochalcogenation of Cyclopropyl Carbaldehydes

Abstract

meso-Cyclopropyl carbaldehydes are treated in the presence of an organocatalyst with sulfenyl and selenyl chlorides to afford 1,3-chlorochalcogenated products. The transformation is achievedb yamergedi minium-enamine activation.T he enantioselective desymmetrization reaction, leadingt ot hree adjacent stereocenters, furnished the target products in complete regioselectivity and moderate to high diastereo-and enantioselectivities (d.r.u pt o15:1a nd e.r.upt o9 3:7).Because of their high strain energy (about 27.5 kcal mol À1

Lewis Acid Catalyzed Enantioselective Desymmetrization of Donor–Acceptor meso‐Diaminocyclopropanes

“…[2] Our group applied aD YKATf or the first time to donoracceptor aminocyclopropanes (Scheme 1). [4] Herein, we present the first enantioselective desymmetrization of nitrogen-substituted cyclopropanes through the Friedel-Crafts alkylation of indoles with ac opper catalyst bearing an unprecedented bis(oxazoline) (BOX) ligand (Scheme 1B). In contrast, the desymmetrization of achiral meso substrates often enables the more straightforward development of enantioselective transformations.…”

“…Thus far,only nucleophile,base,and amine (via iminium-enamine intermediates) catalysts have been reported for the desymmetrization of donor-acceptor meso-cyclopropanes (Scheme 1C). [4] Herein, we present the first enantioselective desymmetrization of nitrogen-substituted cyclopropanes through the Friedel-Crafts alkylation of indoles with ac opper catalyst bearing an unprecedented bis(oxazoline) (BOX) ligand (Scheme 1B). This method delivers enantioenriched urea derivatives as products,w hich are highly important core structures in natural products and bioactive compounds,such as tulongicin A( 3), [5a] biotin (4), [5b] or (À)-agelastatin A (5; [5c-d] Figure 1).…”

Carboxylates as Nucleophiles in the Enantioselective Ring‐Opening of Formylcyclopropanes under Iminium Ion Catalysis

“…[7] It shouldb e highlighted that av ariety of heteronucleophiles have been previously used to promote ring-opening on donor-acceptor cyclopropanes, [8] typicallyr equiring powerful nucleophiless uch as amines, azides, halides, or indoles. [12] These two reports rely on the use of ac hlo- ride anion as the nucleophilic speciest hat promote the ringopeningo ft he cyclopropyliminium ion intermediate [13] and also show the necessity of an external electrophilics ulfur or halogen source to quench the enamine formed after the ringopeningr eactiona sacommon feature, in contrast to the reaction studied herein. Sparr and Gilmour were pioneers in reporting the enantioselective ring-opening of formylcyclopropanes under iminium activation using MacMillantype imidazolidinonesa sc atalysts in the presence of chloride and N-chlorosuccinimide,l eading to a,g-dichlorinated aldehydes.…”

Lewis Acid Catalyzed Stereoselective Dearomative Coupling of Indolylboron Ate Complexes with Donor–Acceptor Cyclopropanes and Alkyl Halides

“…The cascade features the formation of three C À Cb onds and allows the construction of up to three contiguous stereocenters,i ncluding aq uaternary center (Scheme 1C). [15,16] We commenced our studies by examining the reaction of diethyl 2-phenylcyclopropane-1,1-dicarboxylate (3a)with the boron ate complex generated from indol-2-yllithium 1a [17] and phenylboronic ester 2a.Methyl iodide (4a)was chosen as the fourth reaction component (see the Supporting Information for details). [14] In contrast to prior studies on D-A cyclopropane ring opening, [10] the present contribution shows the first 1,3-difunctionalizationofD-A cyclopropanes, in which both donor and acceptor carbon atoms of the cyclopropane moiety undergo CÀCbond formation, that does not involve cyclization.…”

“…[14] In contrast to prior studies on D-A cyclopropane ring opening, [10] the present contribution shows the first 1,3-difunctionalizationofD-A cyclopropanes, in which both donor and acceptor carbon atoms of the cyclopropane moiety undergo CÀCbond formation, that does not involve cyclization. [15,16] We commenced our studies by examining the reaction of diethyl 2-phenylcyclopropane-1,1-dicarboxylate (3a)with the boron ate complex generated from indol-2-yllithium 1a [17] and phenylboronic ester 2a.Methyl iodide (4a)was chosen as the fourth reaction component (see the Supporting Information for details). With the Lewis acid Sc(OTf) 3 (20 mol %) at 60 8 8C for 20 h, the targeted compound 5a was isolated as as ingle diastereoisomer in 22 %yield (Table 1, entry 1).…”