Beyond geminal diesters: increasing the scope of metal-mediated vinylcyclopropane annulations while decreasing pre-activation

Abstract

The utilization of unactivated substrates in annulation reactions provides access to complex products without the need for subsequent removal of the activating group. Vinylcyclopropanes (VCPs), occurring naturally in several monoterpene natural products, are an important building block for organic chemistry, and can be activated by electron withdrawing substituents directly on the cyclopropane to facilitate ring opening reactions. However, many VCPs that lack these activated groups remain reactive with several group 8, 9 and 10 transition metals, by alternative modes of activation, forming metallacycles. These useful intermediates produce annulation products in reactions with unsaturated π-units, providing rapid access to new carbocycles. Several formal cycloadditions that incorporate unactivated VCPs as substrates have been developed, including [5 + 2], [5 + 2 + 1], [5 + 1 + 2 + 1], [3 + 2], [3 + 2 + 1], [5 + 1], and others, using Rh, Ni, Ru, Ir, Fe and Co based catalysts. Mono- and polycyclic ring systems have been made using these methods with their utility demonstrated through the synthesis of complex natural products. This review will summarize the annulations of VCPs that lack geminal diesters, but retain reactivity via transition metal catalysts.

Ni(NHC) Catalyzed Rearrangement of 1‐Acyl‐2‐vinylcyclopropanes: Tackling a Mechanistic Puzzle by Combined Experimental and Computational Studies

“…donor‐acceptor‐substituted vinylcyclopropanes, can react under much milder conditions, eventually promoted by Lewis acids . Furthermore, transition metal‐catalyzed rearrangements have been developed, most notably with Pd, Rh, Ni, Mo, Cr, Cu, Fe and more recently Ir complexes. However, in many cases transition metal catalysts need activated substrates, carrying at least two activating groups (EWG and/or EDG), heteroatoms, dienes, ene‐ynes or allenes.…”

Reaction of 3-Oxa-2-oxobicyclo[4.2.0]oct-4-ene-1-carboxylate with Dimethylsulfoxonium Methylide

“…General Melting point was measured with a Yanaco MP micro-melting point apparatus and are uncorrected. NMR spectra were measured on Bruker Ultrashield 300 ( 1 H: 300 MHz; 13 C: 75 Hz), JEOL ECS-400 ( 1 H: 400 MHz; 13 C: 100 Hz), and Bruker Ascend 500 ( 1 H: 500 MHz; 13 C: 125 Hz) spectrometers with tetramethylsilane as the internal standard. Chemical shift are reported in parts per million.…”

“…[1][2][3][4][5][6][7][8][9][10] Cycloalkanes play an important role in the field of organic synthesis as they can take part in various types of reactions. [11][12][13][14][15][16][17][18][19][20][21][22] These compounds are highly reactive toward ring-opening reactions. The high reactivities can be attributed to the angle and torsional strains.…”

Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes

“…Finally, the last three sections will discuss special classes of cyclopropanes substituted with C–C unsaturations: Vinylcyclopropanes (section ), alkylidenecyclopropanes (section ), and vinylidenecyclopropanes (section ). The presence of the more reactive π systems opens the way for other types of transition-metal-based activations, which has been described in dedicated reviews, − none of them specific to asymmetric transformations however. Cyclopropenes have been only rarely used in asymmetric ring-opening transformations and are not covered in this review …”