Tandem double intramolecular [4 + 2]/[3 + 2] cycloadditions of nitroalkenes

[reaction: see text]. A new class of tandem [4 + 2]/[3 + 2] cycloadditions of nitroalkenes is described in which both pericyclic processes are intramolecular. Two subclasses of intra [4 + 2]/intra [3 + 2] cycloadditions have been explored in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate. For both families of precursors, the cycloadditions occur in good yield and are found to be highly regio- and stereoselective. This method converts linear polyenes to functionalized polycyclic systems bearing up to six stereogenic centers.     

Synthesis of aromatic aldehydes by organocatalytic [4+2] and [3+3] cycloaddition of α,β-unsaturated aldehydes

Organocatalytic inter- and intramolecular [4+2] and [3+3] cycloadditions of α,β-unsaturated aldehydes to give polysubstituted aromatic aldehydes are described. High periselectivity for the cycloadditions, with catalyst effects exerted by l-proline and pyrrolidine-HOAc, as well as cocatalyst, additive effects, has been observed.     

DABCO and Bu(3)P catalyzed [4 + 2] and [3 + 2] cycloadditions of 3-acyl-2H-chromen-ones and ethyl 2,3-butadienoate

DABCO-catalyzed [4 + 2] and Bu(3)P-catalyzed [3 + 2] cycloadditions between 3-acyl-2H-chromen-ones and ethyl 2,3-butadienoate were developed for the synthesis of dihydropyran-fused and cyclopenten-fused chromen-2-ones with high regio- and stereo-selectivities, respectively. The synthetic procedures have the advantages of mild reaction conditions, convenient handling and good atom economy as well as a wide substrate scope, which make this method useful for the synthesis of potentially biologically active dihydropyran-fused and cyclopenten-fused chromen-2-ones derivatives. Possible reaction mechanisms have also been proposed on the basis of previous literature and our investigation.     

Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of trans-vinylcyclopropane-enes

Vinylcyclopropane (VCP) has been well applied as a five-carbon component, rather than a three-carbon component, in transition-metal catalyzed cycloadditions. Here we demonstrate a Rh(I)-catalyzed [3 + 2] reaction of trans-VCP-enes, where VCP acts as a three-carbon synthon to furnish five-membered carbocycles. This novel cycloaddition is efficient in generating bicyclic cyclopentanes in good yields from simple and easily prepared substrates. When cis-VCP-ene is used as the substrate, VCP acts as a five-carbon unit to give a [5 + 2] cycloadduct. Rationalization of the [3 + 2] and [5 + 2] cycloadditions of VCP-enes has been proposed.     

Tandem double intramolecular [4+2]/[3+2] cycloadditions of nitroalkenes. The fused/bridged mode

A new class of tandem [4+2]/[3+2] cycloadditions of nitroalkenes is described in which both pericyclic processes are intramolecular. Two subclasses of intra [4+2]/intra [3+2] cycloadditions have been explored in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate. For both families of precursors, the cycloadditions occur in good yield and are found to be highly regio- and stereoselective. This method converts linear polyenes to functionalized polycyclic systems bearing up to six stereogenic centers.     

Transition metal-catalyzed [4 + 2 + 2] cycloadditions of bicyclo[2.2.1]hepta-2,5-dienes (norbornadienes) and bicyclo[2.2.2]octa-2,5-dienes

The transition-metal-catalyzed [4 + 2 + 2] cycloadditions of norbornadienes, bicyclo[2.2.2]octa-2,5-diene, and benzobarrelene with 1,3-butadienes proceed in excellent yields using cobalt-based catalytic systems. Two key distinctions between these [4 + 2 + 2] cycloadditions and the corresponding transition-metal-catalyzed [2 + 2 +2] reactions of norbornadiene are the requirement of a bimetal catalytic system with a bisphosphine ligand for the former and exclusive regioselectivity in the [4 + 2 + 2] reaction of 2-substituted norbornadienes to produce 1-substituted adducts. These distinctions may indicate two distinct mechanisms for the [4 + 2 + 2] and [2 + 2 + 2] reactions.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Efficient synthesis of methylenetetrahydrofurans and methylenepyrrolidines by formal [3+2] cycloadditions of propargyl substrates

Recent developments concerning the synthesis of methylenetetrahydrofurans and methylenepyrrolidines by one-pot formal [3+2] cycloadditions involving propargylic (and allylic) alcohols and amines with electrophilic alkenes are described. The synthetic methods provide powerful tools to prepare highly functionalized oxygen- and nitrogen-containing five-membered ring systems. The reactions can be effectively promoted by base, base/transition metals, and Lewis acids, depending on the substrates.     

[2+1] Cycloaddition Affording Methylene‐ and Vinylidenecyclopropane Derivatives: A Journey around the Reactivity of Metal‐Phosphinito–Phosphinous Acid Complexes

Metal–phosphinito–phosphinous acid complexes are interesting catalysts exhibiting unique reactivities. In this account, we intend to provide a clear overview of palladium– and platinum–phosphinito–phosphinous acid complexes, their preparation from secondary phosphine oxides, and their applications in catalysis. They have been mainly used to develop [2+1] cycloadditions to afford methylenecyclopropane derivatives using norbornenes and various alkynes as partners. As a function of the catalyst, the reaction conditions, or the nature of the reagents, different synthetic transformations have been observed: [2+1] cycloadditions, giving rise to either alkylidenecyclopropanes or vinylidenecyclopropanes; tandem [2+1]/[3+2] cycloadditions, and so forth. The mechanisms of these reactions have been studied to rationalize the different reactivities observed.     

A novel synthesis of enantiopure octahydropyrrolo[3,4-b]pyrroles by intramolecular [3 + 2] dipolar cycloaddition on chiral perhydro-1,3-benzoxazines

[reaction: see text] Condensation of N-substituted glycines with chiral 3-allyl-2-formyl perhydro-1,3-benzoxazines forms an azomethine ylide that cyclizes to give octahydropyrrolo[3,4-b]pyrrole derivatives. The [3 + 2] dipolar cycloadditions are stereoespecific leading to a single diastereoisomer. The chemical yields are dependent on the reaction temperature and the presence or absence of a base.     

Rhodium-catalysed chemo- and regio-selective [3 + 2+2] cycloadditions of bis(methylenecyclopropanes) and alkynes: Synthesis of spirocyclic 5–7 condensed cycloheptenes

Abstract

Rhodium-catalyzed intermolecular [3?+?2+2] cycloaddition reactions of bis(methylenecyclopropanes) with different alkynes are described. The rhodium-catalyzed [3?+?2+2] cycloadditions resulted in the formation of functionalized 5–7–3 spirocyclic carbocycles in moderate yields with excellent regio- and chemo-selectivity.     

Enantioselective Formal [4+2] Cycloadditions to 3‐Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles

The first enantioselective formal [4+2] cycloadditions of 3‐nitroindoles are presented. By using 3‐nitroindoles in combination with an organocatalyst, chiral dihydrocarbazole scaffolds are formed in moderate to good yields (up to 87 %) and enantioselectivities (up to 97 % ee). The reaction was extended to include enantioselective [4+2] cycloadditions of 3‐nitrobenzothiophene. The reaction proceeds through a [4+2] cycloaddition/elimination cascade under mild reaction conditions. Furthermore, a diastereoselective reduction of an enantioenriched cycloadduct is presented. The mechanism of the reaction is discussed based on experimental and computational studies.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Simultaneous discrimination of diastereotopic groups and faces: the first example in intramolecular [3+2] and [2+2+1] cycloaddition reactions

To explore a novel concept for controlling diastereoselectivity, systematic studies on the sense and degree of diastereotopic groups and face selections in intramolecular [3 + 2] (nitrile oxide and nitrone) and [2 + 2 + 1] (Pauson-Khand) cycloadditions have been conducted. Optically pure methyl (S)-3,4-O-isopropylidene-3,4-dihydroxybutanoate (5) and methyl (S)-2,3-O-isopropylidene-2,3-dihydroxypropanoate (6) were converted to substrate aldehydes (1-4) that bear geminal allyl groups and four types of controllers with the intention of imparting a stereochemical bias to the allylic groups and their faces. The controllers involve 1,2-bis(tert-butyldimethylsiloxy), 1,3-bis(tert-butyldimethylsiloxy), 1,2-acetonide, and 1,3-acetonide groups, which are referred to as 1,2-(TBDMSO)(2), 1,3-(TBDMSO)(2), 1,3-dioxolane, and 1,3-dioxane, respectively. Twelve runs of cycloaddition reactions as combinations between the three types of reactions and the four types of substrates were performed to provide bicyclo[4.3.0] or -[3.3.0] adducts of synthetic importance in which isoxazolidine, isoxazoline, or cyclopentenone segments were fused. For every case, high levels of diastereoselectivity have been achieved: >99% (in eight cases), 82%, and 76% for the discrimination of diastereotopic groups and 68-->99% for the discrimination of diastereotopic faces. On the basis of the absolute structures of the cycloadducts, plausible stereochemical models are proposed.     

Palladium-catalyzed asymmetric [3 + 2] trimethylenemethane cycloaddition reactions

Transition-metal-catalyzed trimethylenemethane (TMM) [3 + 2] cycloadditions provide direct routes to functionalized cyclopentanes. This reaction has been shown to be a highly chemo-, regio-, and diastereoselective process. We report a palladium-catalyzed asymmetric [3 + 2] trimethylenemethane (TMM) cycloaddition between 3-acetoxy-2-trimethylsilylmethyl-1-propene and various di- and trisubstituted olefins. Yields of exo-methylenecyclopentane products range from 59 to 99%, and enantiomeric excesses range from 58 to 92% ee.     

3-nitrocoumarins as dienophiles in the Diels-Alder reaction in water. An approach to the synthesis of nitrotetrahydrobenzo[c]chromenones and dihydrodibenzo[b,d]furans

The [4 + 2] cycloadditions of 3-nitrocoumarin (1a), 6-chloro-3-nitrocoumarin (1b), and 6-, 7-, and 8-hydroxy-3-nitrocoumarins (1c, 5, and 6) with (E)-piperylene (7), isoprene (8), 2,3-dimethyl-1,3-butadiene (9), 2-methoxy-1,3-butadiene (10), 2,3-dimethoxy-1,3-butadiene (11), and cyclopentadiene (12) were investigated in aqueous medium, in organic solvent and under solventless conditions. The reactions performed in water occurred in heterogeneous phase but were faster than those executed in toluene or dichloroethane (DCE). 1a-c, 5, and 6 behaved as 2pi components in the Diels-Alder cycloadditions with 7-10 and 12, and exo adducts were preferentially or exclusively produced. Surprisingly 1a, behaved as a 4pi component in the cycloaddition in water with 11 and 4-substituted 3-nitrochromanones 20 and 21 were isolated. The cycloadditions of hydroxy-3-nitrocoumarins 1c, 5, and 6 with 1,3-diene 9 did not work in water or in organic solvent, but did work under solventless conditions. Nitrotetrahydrobenzo[c]chromenones 13-16, 24, and 25, originating from the normal electron-demand Diels-Alder reactions, were converted into dihydrodibenzo[b,d]furans 27-31 in water, via one-pot Nef-cyclodehydration reactions.     

Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions

Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.     

Cyclobutane and Cyclobutene Synthesis: Catalytic Enantioselective [2+2] Cycloadditions

Cyclobutanes and cyclobutenes are important structural motifs found in numerous biologically significant molecules, and they are useful intermediates for chemical synthesis. Consequently, [2+2] cycloadditions to access cyclobutanes and cyclobutenes have been established to be particularly useful transformations. Within the last 10 years, an increase in the frequency of publications for catalytic enantioselective [2+2] cycloadditions has occurred. These reactions provide access to a wide array of enantiomerically enriched chemical diversity that was not previously attainable. Described in this review are the advances made in catalytic enantioselective [2+2] cycloadditions to access cyclobutanes and cyclobutenes.     

Rhodium N-heterocyclic carbene-catalyzed [4 + 2] and [5 + 2] cycloaddition reactions

[reactions: see text] A rhodium complex of N-heterocyclic carbene (NHC) has been developed for intra- and intermolecular [4 + 2] and intramolecular [5 + 2] cycloaddition reactions. This is the first use of a transition-metal NHC complex in a Diels-Alder-type reaction. For the intramolecular [4 + 2] cycloaddition reactions, all the dienynes studied were converted to their corresponding cycloadducts in 91-99% yields within 10 min. Moreover, up to 1900 turnovers have been obtained for the intramolecular [4 + 2] cycloaddition at 15-20 degrees C. For the intermolecular [4 + 2] cycloadditions, high yields (71-99%) of the corresponding cycloaddition products were obtained. The reaction time and yield were highly dependent upon the diene and the dienophile. For the intramolecular [5 + 2] cycloaddition reactions, all the alkyne vinylcyclopropanes studied were converted to their corresponding cycloadducts in 91-98% yields within 10 min. However, the catalytic system was not effective for an intermolecular [5 + 2] cycloaddition reaction.     

High pressure [4+2] and [2+2+2] reactions between cycloheptatriene and methyl propiolate

Under high pressure conditions, cycloheptatriene reacts with methyl propiolate to afford mono-, bis- and trisadducts all retaining, the norcaradiene structure. The four new compounds are formed via [4+21] and [2+2+2] cycloadditions. The latter are examples for the high pressure extension of the scope of homo-Diels-Alder reactions.