Radical [3+2] annulation of N-allyl-N-chlorotosylamide with alkenes via atom-transfer process

[reaction: see text]. A radical [3+2] annulation reaction with an N-centered radical has been developed. The reaction of alkenes with N-allyl-N-chlorotosylamide yields the corresponding pyrrolidine derivatives in good yields in the presence of Et3B as a radical initiator.     

Regioselective intramolecular [3+2] annulation of allene-nitrones

The regioselective intramolecular 1,3-dipolar cycloaddition of the phenylsulfonylallene-nitrone derivatives has been developed. This reaction showed that the distal double bond of the allene exclusively reacted with the nitrone group to produce the bicyclic isoxazolidine derivatives regardless of the substitution pattern on the allenyl moiety.     

Divergent amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates with electron-deficient alkenes

An amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates 2 with electron-deficient alkenes or diazenes has been developed for efficient syntheses of highly functionalized cyclohexenes, tetrahydropyridazines, and important spirocycles. This reaction unveils a new reactivity pattern of the intensely studied allylic compounds 2 acting as a C(4) synthon in Lewis base catalyzed annulation reactions and also showcases divergent catalysis between tertiary amines and phosphines.     

A [3+2] annulation procedure for methylenecyclopentanes

A two step sequence converts certain cyclic enones to fused methylenecyclopentanes using the annulation reagent 2-chloromethyl-3-trimethylsilylpropene.     

Phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles and allenoates

The efficient phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles with allenoates has been successfully developed, providing a facile access to cyclopenta[b]indolines with good to excellent yields and high diastereoselectivities. This strategy features mild reaction conditions, high functional group tolerance, and scalability. Additionally, the 2-nitrobenzofuran and 2-nitrobenzothiophene were good dearomative [3+2] annulation partners.     

Electrocatalytic formal [2+2] cycloaddition reactions between anodically activated enyloxy benzene and alkenes

Electrocatalytic formal [2+2] cycloadditions between anodically activated enyloxy benzene and alkenes have been accomplished in a lithium perchlorate/nitromethane electrolyte solution. The enyloxy benzene moiety of these electrolytic substrates played an important role in the formation of a radical cation that could accept nucleophilic alkenes, followed by intramolecular electron transfer between the cyclobutane and phenyl ether moieties of the intermediates.     

Radical α-addition involved electrooxidative [3 + 2] annulation of phenols and electron-deficient alkenes

An electrooxidative [3 + 2] annulation of phenols and electron-deficient alkenes for the synthesis of C3-functionalized 2-aryl-2,3-dihydrobenzofuran derivatives was achieved. The ring construction starts by a unique α-addition of carbon radicals derived from anodic oxidation of phenols to electron-deficient alkenes. The subsequent anodic oxidation of the resulting alkyl radical intermediates followed by trapping with the phenolic hydroxy group assembles the 2,3-dihydrobenzofuran core. Such a pathway enables the installation of various electrophilic functionalities including alkoxycarbonyl, alkylaminocarbonyl, trifluoromethyl, and cyano groups at the C-3 of the 2,3-dihydrobenzofuran framework, which is unattainable by other intermolecular reactions. The application of this method for a rapid synthesis of a bioactive natural product is demonstrated.

An electrooxidative [3 + 2] annulation between phenols and electron-deficient alkenes for the synthesis of C3-functionalized 2-aryl-2,3-dihydrobenzofuran derivatives is described.     

Phosphine-catalyzed cascade [3 + 2] cyclization-allylic alkylation, [2 + 2 + 1] annulation, and [3 + 2] cyclization reactions between allylic carbonates and enones

The phosphine-catalyzed annulations between Morita-Baylis-Hillman adduct carbonates and enones are reported. Under the catalysis of PBu(3) (20 mol %), cascade [3 + 2] cyclization-allylic alkylation, [2 + 2 + 1] annulation, and [3 + 2] cyclization reactions chemoselectively occur depending on the substituent variation of both the carbonate and enone. These reactions provide efficient syntheses of highly functionalized cyclopentenes and cyclopentanes.     

Catalytic enantiospecific [3+2] annulation of aminocyclopropanes with ketones

An almost familiar ring: The first enantiospecific [3+2] annulation of donor-acceptor aminocyclopropanes with ketones is reported (see scheme; Phth=phthaloyl). The reaction is catalysed by tin(IV) chloride (5?mol?%) at -78?°C and gives aminotetrahydrofurans bearing a quaternary C5 atom in high yield, diastereoselectivity and enantiospecificity (see scheme).     

Photoredox-catalyzed [4+2] annulation of cyclobutylanilines with alkenes,alkynes, and diynes in continuous flow

Continuous flow has recently emerged as a powerful enabling technology that greatly improves many reactions’ efficiency. Here, we apply the technology to intermolecular [4+2] annulation of cyclobutylanilines with alkenes, alkynes, and diynes by photoredox catalysis. An across-the-board improvement in the annulation’s efficiency is noticed. Moreover, a gram-scale annulation is successfully demonstrated in continuous flow using a much lower catalyst loading.     

Gold-catalyzed intermolecular reactions of propiolic acids with alkenes: [4 + 2] annulation and enyne cross metathesis

A gold-catalyzed intermolecular reaction of propiolic acids with alkenes led to a [4 + 2] annulation or enyne cross metathesis. The [4 + 2] annulation proceeds with net cis-addition with respect to alkenes and provides an expedient route to α,β-unsaturated δ-lactones, for which preliminary asymmetric reactions were also demonstrated. For 1,2-disubstituted alkenes, unprecedented enyne cross metathesis occurred to give 1,3-dienes in a completely stereospecific fashion. DFT calculations and experiments indicated that the cyclobutene derivatives are not viable intermediates and that the steric interactions during concerted σ-bond rearrangements are responsible for the observed unique stereospecificity.     

Silver-catalyzed [3+2+1] annulation of aryl amidines with benzyl isocyanide

A silver-catalyzed [3+2+1] annulation of amidines with benzyl isocyanide toward 2,4-diaryl-1,3,5-triazines was developed. A variety of symmetrical and unsymmetrical products were obtained in moderate to good yields. This work also features an oxidant-free approach to 2,4-disubstituted triazines.     

Synthesis of psudoheliotridane via formal [3+2] annulation and ring-closing metathesis

Base-induced coupling/cyclization stepwise [3+2] annulation of α-sulfonylacetamide with (Z)-2-bromoacrylates yielded polysubstituted pyroglutamates with three contiguous chiral centers with trans-trans orientation in a one-pot synthesis. The pyrrolizidine skeleton was obtained via the ring-closing metathesis (RCM) method. This facile strategy was used to synthesize psudoheliotridane.     

Phosphine triggered [3+2] allenoate-acrylate annulation: a mechanistic enlightenment

A mechanistic study of phosphine-mediated [3+2] annulation of allenoate and acrylate is presented. The insight gained has identified that (1) [3+2] cycloaddition proceeds through a stepwise mechanism and (2) the involvement of a molecule of water, which services as a proton-shuttle, is essential for annulated product formation.     

Highly diastereo- and enantioselective NHC-catalyzed [3+2] annulation of enals and isatins

The chiral N-heterocyclic carbene bearing a proximal hydroxy group derived from L-pyroglutamic acid was found to be an efficient catalyst for the [3+2] annulation of enals and isatins to give the corresponding spirocyclic oxindolo-γ-butyrolactones in good yield with good diastereo- and enantioselectivities.     

Intramolecular [2 + 2]cycloadditions of dialkylketenes with alkenes. Regiochemistry of intramolecular [2+2]cycloadditions of ketenes with alkenes

Unsaturated dialkylketenes 7a, 7b and 7c undergo intramolecular [2 + 2]cycloadditions to give 8a (45%), 9b (23%) and 9c (45%). Intramolecular cycloadditions of dialkylketenes give higher yields than intramolecular cycloadditions of monoalkylketenes, even though dialkylketenes are less reactive than monoalkylketenes. An intramolecular competition experiment with ketene 17 establishes that trans-alkenes are approximately 33 times more reactive than cis-alkenes in intramolecular cycloadditions. Ketene 36 furnishes 22% of the expected bicyclo[3.2.0]heptanone 37 and 28% of bicyclo[3.1.1]heptanone 38.     

[2+3] Cyclopentene annulation and other trimethylsilyl iodide-mediated rearrangement pathways of vinylcyclopropanes

Vinylcyclopropanes of type 2 were converted to either annulated cyclopentenes of type 3 or bicyclo [3.2.1] octenes of type 4 through carefully controlled rearrangement pathways. Factors affecting these rearrangements and their utility in synthesis are described.