Recent Developments in The [5+2] Cycloaddition

Abstract

The [5+2] cycloaddition allows the synthesis of a diversity of complex highly functionalized seven-membered products in a single step. These cycloadducts can readily be further manipulated synthetically for use in the synthesis of a number of complex natural products and important biologically active products containing seven-membered rings. In addition to the common and highly efficient [5+2] cycloadditions of (oxido)pyrylium and (oxido)pyridinium ions with various p-systems, providing an easy access to a wide range of novel heterocyclic sevenmembered rings exhibiting an oxygen or nitrogen bridge, the metal-catalyzed [5+2] cycloadditions still attract a great attention and have become one of the most popular ways of constructing seven-membered compounds. Among the most important reactions are metal-catalyzed (hetero) [5+2] cycloadditions of vinyl-substituted three-membered rings, rhodium-catalyzed [5+2] cycloadditions of 3-acyloxy-1,4-enynes, and metal-catalyzed [5+2] cycloadditions of ortho-vinylphenols and ortho-vinyl/arylanilines. Scheme 1. The metal-catalyzed [5+2] cycloaddition of vinylcyclopropanes and possible mechanisms.Scheme 2. First examples of rhodium-catalyzed intermolecular [5+ +2] cycloadditions of vinylcyclopropanes.Scheme 3. The [5+2] cycloaddition of a vinylcyclopropane and propargyltrimethylsilanes catalyzed with [Rh(C 10 H 8 )(cod)] + SbF 6 À and a tandem [5+ +2] cycloaddition/ protodesilylation reaction. Scheme 4. Three-component domino/tandem [5+2] cycloaddition/vinylogous Peterson/[4+2] cycloaddition reactions of a vinylcyclopropane, 4-(trimethylsilyl)but-2-yn-1-ol and alkenes/alkynes catalyzed with [Rh(Naph)(cod)] + SbF 6 À . Scheme 5. The [5+2] cycloaddition of a vinylcyclopropane and a dimethylalleneyne catalyzed with [Rh(CO) 2 Cl] 2 . Scheme 6. Iridium-catalyzed [5+2] cycloadditions of vinylcyclopropanes and alkynes. Scheme 7. First examples of rhodium-catalyzed intramolecular [5+2] cycloadditions of vinylcyclopropanes with various p-systems. Scheme 8. Intramolecular [5+2] cycloaddition of vinylcyclopropanes and alkynes catalyzed with [{Ir(dbcot)Cl} 2 ]. Scheme 14. Rhodium-catalyzed intramolecular hetero [5+2] cycloaddition of vinyloxiranes and alkynes. Scheme 25. Dearomative indole [5+2] cycloadditions of oxidopyrylium ions and alkenes. Scheme 26. Type 2 [5+2] cycloadditions of oxidopyrylium ions and alkenes or alkyne. Scheme 45. Scandium-catalyzed [5+2] cycloaddition of N-indolyl alkylidene b-amide esters and alkenes. Scheme 51. Rhodium-catalyzed domino [3+2] cycloaddition/[5+2] cycloaddition reactions of 4-aryl-1,2,3-triazoles and internal alkynes.

Cobalt-Mediated η5-Pentadienyl/Alkyne [5 + 2] Cycloaddition Reactions: Substitution Effects, Bicyclic Synthesis, and Photochemical η4-Cycloheptadiene Demetalation

“…While still an underexplored reaction, the metal-mediated [5 + 2] cycloaddition manifold is becoming increasingly utilized by the synthetic community . Here we have established the synthetic scope of the cobalt-mediated pentadienyl/alkyne [5 + 2] cycloaddition reaction.…”

“…In contrast, the preparation of seven-membered rings by cycloaddition remains less developed, despite the almost continuous discovery of bioactive natural products with seven-membered-ring structures in the core . One important pathway to access the seven-membered ring is the formal [5 + 2] cycloaddition reaction, which has a rich and varied history . Among unsolved problems in [5 + 2] cycloaddition is the cyclization of an alkyne with a pentadienyl fragment, a reaction that generally requires mediation by a transition metal .…”

Synthesis of Oxa-Bridged Medium-Sized Carbocyclic Rings via Prins Cyclization

“…Due to their unique structures as well as their biological importance, these oxa-bridged medium-sized carbocycles have attracted considerable attention from the synthetic community . To date, numerous methodologies, such as gold-catalyzed alkyne cycloisomerization reactions, Lewis acid mediated intramolecular cross-cycloadditions, photoinduced cyclizations, 1,3-dipolar cycloadditions, [5 + 2] dipolar cycloaddition of oxidopyrylium ylides, , ring-closing metathesis (RCM), Prins-type cyclizations, and [4 + 3] cycloadditions have been developed for the synthesis of OBB ring systems. Despite the above-mentioned methods, practical and flexible strategies (i.e., short steps, cheap commercially available starting materials and reagents, easy-to-handle reaction conditions, gram-scale procedure, and stereoselectivity) leading to the synthesis of seven-, eight-, and nine-membered rings are still in great demand. , In this paper, we report a Lewis-acid-mediated Prins cyclization approach for constructing medium-sized carbocycles bearing oxa-bridged bicyclic structural units.…”

Catalytic Enantioselective Intermolecular [5 + 2] Dipolar Cycloadditions of a 3-Hydroxy-4-pyrone-Derived Oxidopyrylium Ylide

“…The [5 + 2] dipolar cycloaddition of oxidopyrylium ylides enables facile access to the 8-oxabicyclo[3.2.1]­octane scaffold and has been widely used in target-oriented synthesis . In addition to being a prevalent substructure in bioactive natural products, 8-oxabicyclo[3.2.1]­octanes provide an entrée into functionalized tetrahydrofurans and cycloheptanes. , These two ring systems are of high interest to synthetic chemists, with the latter being relatively challenging to construct due to ring-strain and entropic considerations …”

“…Both of these prior studies leveraged carboxylate elimination of acyloxypyran to generate reactive oxidopyrylium ylides, which is the method most commonly associated with oxidopyrylium [5 + 2] cycloadditions. , Less studied intermediates to oxidopyrylium ylides are 3-hydroxy-4-pyrones ( 9 , Scheme ), which are classically converted to the active oxidopyrylium ylides through thermal group transfer ( 9 → 10a ) and trapped by a tethered alkene or alkyne. , Intermolecular 3-hydroxy-4-pyrone-based oxidopyrylium cycloadditions, on the other hand, can be performed by first converting the pyrone to 3-hydroxy-4-methoxypyrylium triflate salts ( 11 ) and then deprotonating them with aniline bases in the presence of the dipolarophile . We further adapted this intermolecular reaction through our recent discovery that oxidopyrylium dimers ( 12 ) can be used as the source of the oxidopyrylium ylide, thereby eliminating conjugate acid and residual base present in the in situ deprotonation protocol .…”