Bispericyclic Diels-Alder Dimerization of ortho-Quinols in Natural Product (Bio)Synthesis: Bioinspired Chemical 6-Step Synthesis of (+)-Maytenone.

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2-alkylphenolic precursors into 6-alkyl-6-hydroxycyclohexa-2,4-dienones. These so-called ortho-quinols cyclodimerize via a remarkably selective bispericyclic Diels-Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho-quinols can be chemically reproduced in the laboratory with the same strict level of site-specific regioselectivity and stereoselectivity.

Minisci-Photoredox-Mediated α-Heteroarylation of N-Protected Secondary Amines: Remarkable Selectivity of Azetidines.

The development of a general, mild, and functional-group-tolerant direct functionalization of N-heteroarenes by C-H functionalization with N-protected amines, including azetidines under Minisci-mediated photoredox conditions, is reported. A broad scope of substituted azetidines, including spirocyclic derivatives, and heterocycles were explored. This reaction enables the production of sp3-rich complex druglike structures in one step from unactivated feedstock amines and heterocycles.

Asymmetric Alkynylation of β-Ketoesters and Naphthols Promoted by New Chiral Biphenylic Iodanes.

The preparation of new chiral biphenylic λ -iodane reagents bearing transferable alkynyl ligands is described. These reagents transfer their carbon-based ligands onto β-ketoesters with an enantiomeric excess (ee) up to 68 %, and most remarkably, enable the dearomative alkynylation of naphthols in good to high yields up to 84 % ee.

Iron-Catalyzed Synthesis of Sulfur-Containing Heterocycles.

An iron-catalyzed synthesis of sulfur- and sulfone-containing heterocycles is reported. The method is based on the cyclization of readily available substrates and proceeded with high efficiency and diastereoselectivity. A variety of sulfur-containing heterocycles bearing moieties suitable for subsequent functionalization are prepared.

Total Synthesis of (-)-Bacchopetiolone via an Asymmetric Hydroxylative Phenol Dearomatization/[4+2]-Dimerization Cascade Promoted by a Novel Salen-Type Chiral Iodane.

The first total and biomimetic synthesis of the natural bis(sesquiterpene) (-)-bacchopetiolone (revised structure) was completed through a highly diastereoselective hydroxylative phenol dearomatization/[4+2]-dimerization cascade conversion of (+)-curcuphenol using a novel C2-symmetrical chiral Salen-type bis(λ(5)-iodane).

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics.

Alkenes containing N-heteroaromatics are known to be poor partners in cross-metathesis reactions, probably due to catalyst deactivation caused by the presence of a nitrogen atom. However, some examples of ring-closing and cross-metathesis involving alkenes that incorporate N-heteroaromatics can be found in the literature. In addition, recent mechanistic studies have focused on the rationalization of nitrogen-induced catalysts deactivation.

Iron-Catalyzed Synthesis of C2 Aryl- and N-Heteroaryl-Substituted Tetrahydropyrans.

An iron-catalyzed cyclization of hydroxy allylic derivatives into tetrahydropyrans possessing an N-heteroaryl at C2 is disclosed. The reaction proceeds with good yield and in high diastereoselectivity in favor of the more stable isomer. The diastereoselectivity results from an iron-induced reopening of the tetrahydropyrans, allowing a thermodynamic equilibration.

Asymmetric hydroxylative phenol dearomatization promoted by chiral binaphthylic and biphenylic iodanes.

The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues.