Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings

Abstract

The efficient and selective synthesis of functionalized seven‐membered rings remains an important pursuit within synthetic organic chemistry, as this motif appears in numerous drug‐like molecules and natural products. Use of cycloaddition reactions remains an attractive approach for their construction within the perspective of atom and step economy. Additionally, the ability to combine multiple components in a single reaction has the potential to allow for efficient combinatorial strategies of diversity‐oriented synthesis. The inherent entropic penalty associated with achieving these transformations has impressively been overcome with development of catalysis, whereby the reaction components can be pre‐organized through activation by transition‐metal‐catalysis. The fine‐tuning of metal/ligand combinations as well as reaction conditions allows for achieving chemo‐, regio‐, diastereo‐ and enantioselectivity in these transformations. Herein, we discuss recent advances in transition‐metal‐catalyzed construction of seven‐membered rings via combination of 2–4 components mediated by a variety of metals. An emphasis is placed on the mechanistic aspects of these transformations to both illustrate the state of the science and to highlight the unique application of novel processes of transition‐metals in these transformations.

Intermolecular [5+2] Annulation between 1‐Indanones and Internal Alkynes by Rhodium‐Catalyzed C–C Activation

“…[1] They also frequently appear in emerging non-planar organic materials. [2] Compared to five or six-membered rings,significant challenges remain for synthesizing medium-sized cycloheptanes due to limited disconnection approaches and increased activation enthalpy during the ring-forming processes.A mong established seven-membered-ring construction methods, [3] formal [5+ +2] cycloadditions-the annulations between af ive-carbon synthon and at wo-carbon one-have proved to be highly versatile and effective (Scheme 1a). [4] They render multiple C À Cbond formations in one step in an atom-economical, [3] regio-and stereo-selective manner,a nd have found wide success in elegant syntheses of complex natural products.…”

“…[2] Compared to five or six-membered rings,significant challenges remain for synthesizing medium-sized cycloheptanes due to limited disconnection approaches and increased activation enthalpy during the ring-forming processes.A mong established seven-membered-ring construction methods, [3] formal [5+ +2] cycloadditions-the annulations between af ive-carbon synthon and at wo-carbon one-have proved to be highly versatile and effective (Scheme 1a). [4] They render multiple C À Cbond formations in one step in an atom-economical, [3] regio-and stereo-selective manner,a nd have found wide success in elegant syntheses of complex natural products. [4] While the two-carbon synthons generally come from readily available alkenes and alkynes,t he corresponding five-carbon moieties,s uch as vinylcyclopropanes, [5] (oxido)pyrylium ions, [6] 3-acyloxy-1,4-enynes [7] and pentadienyl-metal complexes, [8] are less accessible,w hich typically contain high-energy or special functional groups (FGs) and need to be prepared through multi-step sequences.…”

Metal‐Free, Base‐Promoted, Tandem Pericyclic Reaction: A One‐Pot Approach for Cycloheptane‐Annelated Chromones from γ‐Alkynyl‐1,3‐Diketones

“…The synthesis of carbocyclic seven‐membered or larger rings remains a major challenge in modern synthetic chemistry [1] . These ring systems are medically relevant because they are found in many polycyclic natural products and drug‐like compounds, including tilifolidione, [2a] flueggenoids, [2b,c] and colchicine [2d,e] . Additionally, these carbocycles have shown wide applicability in the material and pharmaceutical sciences [3]…”

Intermolecular [5+2] Annulation between 1‐Indanones and Internal Alkynes by Rhodium‐Catalyzed C–C Activation

“…[1] They also frequently appear in emerging non-planar organic materials. [2] Compared to five or six-membered rings,significant challenges remain for synthesizing medium-sized cycloheptanes due to limited disconnection approaches and increased activation enthalpy during the ring-forming processes.A mong established seven-membered-ring construction methods, [3] formal [5+ +2] cycloadditions-the annulations between af ive-carbon synthon and at wo-carbon one-have proved to be highly versatile and effective (Scheme 1a). [4] They render multiple C À Cbond formations in one step in an atom-economical, [3] regio-and stereo-selective manner,a nd have found wide success in elegant syntheses of complex natural products.…”

“…[2] Compared to five or six-membered rings,significant challenges remain for synthesizing medium-sized cycloheptanes due to limited disconnection approaches and increased activation enthalpy during the ring-forming processes.A mong established seven-membered-ring construction methods, [3] formal [5+ +2] cycloadditions-the annulations between af ive-carbon synthon and at wo-carbon one-have proved to be highly versatile and effective (Scheme 1a). [4] They render multiple C À Cbond formations in one step in an atom-economical, [3] regio-and stereo-selective manner,a nd have found wide success in elegant syntheses of complex natural products. [4] While the two-carbon synthons generally come from readily available alkenes and alkynes,t he corresponding five-carbon moieties,s uch as vinylcyclopropanes, [5] (oxido)pyrylium ions, [6] 3-acyloxy-1,4-enynes [7] and pentadienyl-metal complexes, [8] are less accessible,w hich typically contain high-energy or special functional groups (FGs) and need to be prepared through multi-step sequences.…”