ABSTRACT
Herein, we present the formation of acyclic frameworks bearing two consecutive stereocenters of either tertiary or quaternary nature starting from easily accessible cyclopropenes. This holistic approach involves a regio- and diastereoselective hydro- or carboborylation of substituted cyclopropenyl esters. Formation of boronate complexes of the latter via the addition of nucleophiles and subsequent stereospecific 1,2-migration with carbon-carbon bond cleavage delivered the title compounds.
Subject(s)
Carbon , Cyclopropanes , Carbon/chemistry , Catalysis , Cyclopropanes/chemistry , Molecular Structure , StereoisomerismABSTRACT
We present (3+2)- and (4+2)-cycloadditions of donor-acceptor (D-A) cyclopropanes and cyclobutanes with N-sulfinylamines and a sulfur diimide, along with a one-pot, two-step strategy for the formal insertion of HNSO2 into D-A cyclopropanes. These are rare examples of cycloadditions with D-A cyclopropanes and cyclobutanes whereby the 2π component consists of two different heteroatoms, thus leading to five- and six-membered rings containing adjacent heteroatoms.
ABSTRACT
Donor-acceptor (D-A) cyclopropanes have gained increased momentum over the past two decades. The use of these highly strained three-membered entities paved the way to innovative and original transformations yielding complex cyclic and acyclic architectures that otherwise might be difficult to address. Since the fundamentals were laid by Wenkert and Reissig in the late 1970s, the field has flourished impressively including asymmetric transformations as well as elegant synthetic applications in the construction of natural occurring products. In this Account, we aim to highlight especially our efforts in the context of an efficient access to sulfur- and selenium-containing compounds, of either cyclic or open-chain nature, by exploiting D-A cyclopropane chemistry. Light will be shed on the three fundamental transformations: ring-opening reactions, cycloadditions, and rearrangements.Our synthetic endeavors started back in 2011 guided by quantum chemical studies to obtain 3,3'-linked bisthiophenes along with an unprecedented rearrangement delivering sulfur- and selenium-containing cagelike scaffolds. Inspired by these surprising results, we further deepened our efforts to the construction of new sulfur-carbon and selenium-carbon bonds within the context of D-A cyclopropane chemistry. In the first instance, we capitalized on the great versatility of organosulfur and organoselenium compounds regarding their amphiphilic character to act either as nucleophilic or as electrophilic species. By such an approach, ring-openings via a nucleophilic attack of sulfenyl and selenyl halides furnished 1,3-bishalochalcogenated products. A similar protocol led us to a desymmetrization reaction of meso-cyclopropyl carbaldehydes employing novel chiral imidazolidinone organocatalysts. In contrast, electrophilic sulfur was supplied by N-(arylthio)succinimide substrates to access thiolated γ-amino acid derivatives and their selenium equivalents.Combining the highly reactive thiocarbonyl compounds and vicinal donor-acceptor substituted cyclopropanes opened new vistas in the field of atom-economic cycloaddition reactions to build up sulfur-containing heterocycles of various sizes. The first systematic study of such transformations was made by our group in 2017 leading to highly decorated thiolanes, whereas an intramolecular approach furnished thia-[n.2.1]bicyclic ring systems. Our investigations were then successfully extended to the synthesis of tetrahydroselenophenes by using capricious selenoketones. Recently, we were able to yield the unsaturated analogues, selenophenes, by a (3 + 2)-cycloaddition of D-A cyclopropanes with ammonium selenocyanates followed by oxidation. The formal insertion of thioketenes was realized by employing 3-thioxocyclobutanones as surrogates for disubstituted thioketenes to obtain 2-substituted tetrahydrothiophenes bearing a semicyclic double bond via a (3 + 2) spiroannulation/(2 + 2) cycloreversion sequence. Even the formation of seven-membered S-heterocycles was realized by (4 + 3)-cycloaddition processes. In 2016, we demonstrated the synthesis of benzo-fused dithiepines from in situ generated ortho-bisthioquinones, whereas the utilization of thia-Michael systems as a hetero-4π-component delivered tetrahydrothiepine derivatives containing just one sulfur atom embedded in the ring system.
ABSTRACT
Despite the highly strained nature of cyclopropanes possessing three vicinal quaternary carbon stereocenters, the regio- and diastereoselective copper-catalyzed carbomagnesiation reaction of cyclopropenes provides an easy and efficient access to these novel persubstituted cyclopropyl cores with a complete regio- and diastereoselectivity.
ABSTRACT
We propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate-based protic ionic liquids for the ring-opening of donor-acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1-methylimidazolium thiocyanate under mild metal-free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three-membered ring affording pyrrolidine-2-thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time-efficient step. The ability of 1-methylimidazolium thiocyanate to serve as a triplex reagent was exemplarily illustrated by (4+2)-annulation with 1-acyl-2-(2-hydroxyphenyl)cyclopropane, epoxide ring-opening and other organic transformations.
ABSTRACT
The reactivity of donor-acceptor (D-A) cyclopropanes towards thioketenes was investigated. In a (3+2)-cycloaddition using Sc(OTf)3 as a Lewis acidic catalyst, the corresponding exocyclic thioenol ethers (2-methylidene tetrahydrothiophenes) were formed in moderate to good yields. Unsymmetrical thioketenes provided E/Z mixtures at the double bond, with the Z isomer being preferred.
ABSTRACT
Ferrocenyl thioketones reacted with donor-acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2-arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone.
ABSTRACT
A general approach is described for the formation of tetrahydrothiepines using donor-acceptor cyclopropanes. Thiochalcones, functioning as sulfur-containing four-atom building blocks, were reacted in a Lewis acid catalyzed formal (4 + 3)-cycloaddition reaction with donor-acceptor cyclopropanes as three-atom building blocks. Under mild conditions various tetrahydrothiepines were synthesized in good yields in a stereospecific reaction with high functional group tolerance.
ABSTRACT
A 1,3-aminothiolation was realized by reacting 2-substituted cyclopropane 1,1-dicarboxylates with sulfonamides and N-(arylthio)succinimides. Under Sn(OTf)2 catalysis the transformation proceeded smoothly to the corresponding ring-opened products bearing the sulfonamide in the 1-position next to the donor and the arylthio residue in the 3-position next to the acceptor. The procedure was extended to the corresponding selenium analogues by employing N-(phenylseleno)succinimides as an electrophilic selenium source.
ABSTRACT
Donor-acceptor cyclopropanes were reacted under Lewis acid catalysis with 3-thioxocyclobutanones as surrogates for disubstituted thioketenes. A broad scope of 2-substituted tetrahydrothiophenes with a semicyclic double bond was obtained under mild conditions with high functional group tolerance and in excellent yield. A sequence of a formal [3 + 2]-cycloaddition followed by the subsequent release of disubstituted ketene is postulated as the mechanism.
ABSTRACT
The crystal structure of the title compound, C9H6OS2, represents a new polymorph. The crystal structure was solved in the ortho-rhom-bic space group Pbcn with one half of the mol-ecule in the asymmetric unit. The thio-phene rings are perfectly planar and twisted with respect to each other, showing the mol-ecule to be in an S,O-trans/S,O-trans conformation. In the crystal, C-Hâ¯O hydrogen bonds connect the mol-ecules into layers extending parallel to the ab plane. The crystal structure also features π-π inter-actions.
ABSTRACT
Lewis-acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with thioketones are described. Highly substituted tetrahydrothiophenes with two adjacent quaternary carbon atoms were obtained in a stereospecific manner under mild conditions and in high yield when using AlCl3 as Lewis acid. Moreover, an intramolecular approach was successfully implemented to gain access to sulfur-bridged [n.2.1] bicyclic ring systems. Conversion of selenoketones, the heavier analogues, under similar conditions resulted in the formation of various tetrahydroselenophenes.
ABSTRACT
Reactions of 2-arylcyclopropane dicarboxylates with naphthoquinones are reported. The key feature was the use of catalytic amounts of SnCl2 , which acts as both an electron donor and a Lewis acid. By an in situ umpolung of naphthoquinone the formerly electrophilic species is converted into a nucleophile that is able to trigger the ring-opening of the three-membered ring with formation of a new C-C bond. Treatment of these products with base under oxidative conditions resulted-through loss of methyl formate-in cyclopentannulated products with fully conjugated π systems exhibiting intensive absorptions in the visible range.
