Recent advances in transition metal-catalyzed C–H bond functionalization have profoundly impacted synthetic strategy Since organic substrates typically contain several chemically distinct C–H bonds, controlling the regioselectivity of C–H bond functionalization is imperative to harness its full potential Moreover, the ability to alter reaction pathways to selectively functionalize different C–H bonds in a substrate represents a greater opportunity and challenge The choice of catalysts, ligands, solvents, and even more subtle variations of the reaction conditions have been shown to allow the formation of regioisomeric C–H functionalization products starting from the same precursors This review describes recent advances in transition metal-catalyzed divergent C–H bond functionalization that highlight its potential in organic synthesis

Transition metal-catalyzed site- and regio-divergent C–H bond functionalization

This article reviews synthetic transformations involving cleavage of a carbon–carbon bond of a four-membered ring, with a particular focus on the examples reported during the period from 2011 to th...

Cleavage of Carbon-Carbon σ-Bonds of Four-Membered Rings.

The structures of natural products from a variety of sources contain spirocycles, two rings that share a common atom. The spiro motif is finding increasing inclusion in drug candidates, and as a structural component in several promising classes of chiral ligands used in asymmetric synthesis. Total syntheses of products containing all-carbon spirocycles feature several common methods of ring closure which we examine in this review.

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Total syntheses of natural products containing spirocarbocycles

The first total syntheses of taiwaniadducts B, C, and D have been accomplished. Two diterpenoid segments were prepared with high enantiopurity, both through Ir-catalyzed asymmetric polyene cyclization. A sterically demanding intermolecular Diels–Alder reaction promoted by Er(fod)3 assembled the scaffold of taiwaniadducts B and C. A carbonyl-ene cyclization forged the cage motif of taiwaniadduct D at a late stage, providing over 200 mg of this compound.

Total Synthesis of Taiwaniadducts B, C, and D

New perspectives, in particular for the synthesis of isochromane derivatives (see scheme), are provided by the title reaction. Excellent diastereoselectivites are achieved in this reaction which proceeds through a gold-catalyzed 1,3-acyloxy migration. In some cases exclusively the Z isomer is detected.

In Situ Generation of Nucleophilic Allenes by the Gold‐Catalyzed Rearrangement of Propargylic Esters for the Highly Diastereoselective Formation of Intermolecular C(sp3) ? C(sp2) Bonds

A mild and catalyzed alternative to the direct aldol reaction has been developed based on the gold-catalyzed methoxy group transfer from dimethyl acetals to terminal alkynes. Due to the simultaneous activation of the acetals, this aldol approach is only functional for acetals but not aldehydes. A ligand effect from the gold complex has also been observed.

An Alternative Approach to Direct Aldol Reaction Based on Gold‐Catalyzed Methoxyl Transfer

A strategy to the 6-5-6 tricyclic scaffold of taiwaniaquinoids was established on the basis of a one-pot thermal ring expansion/4π-electrocyclization process. The efficiency of this methodology has been demonstrated through its application in the total synthesis of taiwaniaquinone H, which has been accomplished in three steps and 14% overall yield in a protecting-group-free manner starting from commercially available materials.

Protecting-group-free synthesis of taiwaniaquinone H using a one-pot thermal ring expansion/4π-electrocyclization strategy.

The first total synthesis of asterredione was efficiently accomplished over five linear steps and in 21.5% overall yield. As the crucial step, the 2-quaternary 1,3-cyclopentenedione skeleton of asterredione was readily achieved using the Darzens/ring-expansion strategy developed in our laboratory. The structure of synthesized asterredione was fully confirmed by X-ray crystallography.

Total synthesis of asterredione.

Spiroxins A, C and D are metabolites with unique polycyclic structures and intriguing biological activities. Based on a scalable enantioselective epoxidation of 5-substituted naphthoquinone, an oxidation/spiroketalization cascade, ortho -selective chlorination of phenol unit and oxime ester-directed acetoxylation, a divergent and enantioselective synthetic route to (-)-spiroxins A and C and the first total synthesis of (-)-spiroxin D have been achieved. The synthetic compounds provide a good foundation for the investigation of antitumor activity and antibacterial activity of the natural products and their synthetic intermediates.

Enantioselective Total Synthesis of ( – )-Spiroxins A, C and D

A four-electron electrocyclic ring-opening/intermolecular [4+2] cycloaddition of α-hydroxycyclobutenones is reported. The reaction represents the first example for the intermolecular cycloaddition of the extensively studied enol-ketene intermediate, and provides a new synthetic route to multiply substituted δ-lactams in high stereoselectivity.

Four-Electron Electrocyclic Ring-Opening/Intermolecular [4+2] Cycloadditions of α-Hydroxycyclobutenones: Stereoselective Synthesis of Multiple Substituted δ-Lactams

Xiangdong Hu

Papers

An Alternative Approach to Direct Aldol Reaction Based on Gold‐Catalyzed Methoxyl Transfer

Protecting-group-free synthesis of taiwaniaquinone H using a one-pot thermal ring expansion/4π-electrocyclization strategy.

Total synthesis of asterredione.

Enantioselective Total Synthesis of ( – )-Spiroxins A, C and D

Four-Electron Electrocyclic Ring-Opening/Intermolecular [4+2] Cycloadditions of α-Hydroxycyclobutenones: Stereoselective Synthesis of Multiple Substituted δ-Lactams