En Route to Furan-Fused Naphthopyrones: Formal Synthesis of the (+)-Lasionectrin and Its C12-Epimer.

Despite the vast presence of the furan-fused naphthopyrone (FFN) skeleton in many bioactive natural products, such as lasionectrin, at present, a general approach to FFNs has not been developed yet. For that reason, a simple and straightforward synthetic approach consisting of a sequential procedure of a Diels-Alder reaction between 1,3-dimethoxy-benzocyclobutenol I and furan-fused-α,ß-unsaturated-δ-lactones II (via an ο-quinodimethane intermediate III) followed by an oxidative aromatization of the corresponding Diels-Alder adduct IV is reported. Subsequently, the formal synthesis of the (+)-lasionectrin and its C12-epimer was achieved, the latter in only six steps.

A Visible Light Ru-Catalyzed Photoredox Access to Substituted Dihydrofurans.

An efficient, visible light Ru(bpy)3Cl2-catalyzed method for the preparation of 2,3-dihydrofurans is reported. This approach employs 2-bromoketoesters as radical precursors and alkyl enol ethers as acceptors. The photoredox cycle furnishes an oxonium ion that is captured by an internal nucleophile to render the corresponding dihydrofurans. Moreover, the obtained products contain a versatile acetal moiety at C-2, allowing its transformation into a diverse variety of heteroaromatic and nonaromatic compounds. This method could serve as an important tool in the synthesis of complex tetrahydro- and dihydrofurans as well as heteroaromatic structures.

Dibromo-BODIPY as an Organic Photocatalyst for Radical-Ionic Sequences.

A new dibrominated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) is reported as a new metal-free photocatalyst. This BODIPY showed similar optoelectronic, electrochemical, and performance properties to those of Ru(bpy)3Cl2, one of the most common photocatalysts in a known radical-ionic transformation, such as the formation of 1,4-dicarbonyl compounds. Moreover, additional sequences in which the generated oxonium ion is trapped by an internal nucleophile were developed using this BODIPY photocatalyst. These new sequences allowed the straightforward preparation of γ-alkoxylactones, monoprotected 1,4-ketoaldehydes, and dihydrofurans. This new catalyst, the methodology, and the forged functional groups could be important tools in organic synthesis.

Stereoselective Total Synthesis of Aspergillide A: A Visible Light-Mediated Photoredox Access to the Trisubstituted Tetrahydropyran Core.

A stereoselective total synthesis of natural product aspergillide A is reported. The adopted strategy relies on the direct access to the key tetrahydropyran core through a visible light-mediated photoredox reaction from an allylic alcohol and iodoacetic acid. In a single manipulation, a γ-iodo-δ-valerolactone is obtained through an atom transfer radical addition followed by in situ acid-catalyzed lactonization. The obtained lactone possesses three functionalized sites, which were seized to link the required substituents in the final product and thus completing the total synthesis of aspergillide A.

Visible-Light Photocatalytic Preparation of 1,4-Ketoaldehydes and 1,4-Diketones from α-Bromoketones and Alkyl Enol Ethers.

A Ru2+-photocatalyzed, visible-light-mediated ATRA reaction for the straightforward preparation of 1,4-ketoaldehydes, 1,4-diketones, and 1,4-ketoesters, which are of difficult access by other means, is reported herein. This method employs readily accessible α-bromoketones and alkyl vinyl ethers as starting materials, allowing the construction of secondary, tertiary, and challenging quaternary centers. In addition, the synthetic usefulness of this method is illustrated by applying it to the construction of substituted pyrroles.

Stereocontrolled Nucleophilic Addition to Five-Membered Oxocarbenium Ions Directed by the Protecting Groups. Application to the Total Synthesis of (+)-Varitriol and of Two Diastereoisomers Thereof.

A stereodivergent C-glycosidation of carbohydrate-derived lactones can be mediated by the protecting groups and applied to the total synthesis of (+)-varitriol and of two diastereoisomers thereof, which represent an unprecedent use of the protecting groups in the synthesis of a naturally occurring compound. In particular, the stereoselective nucleophile attack for 2,3-trans-substituted five-membered ring oxocarbenium ions is strongly influenced by the presence of aromatic rings in the protecting groups. According to quantum chemical calculations, the stereoselectvity depends on the π-π interactions between the aromatic ring of the C-2 protecting group with the exocyclic triple bond and the oxocarbenium ion. These interactions account for the stabilization of the conformer in which the C-2 and C-3 substituents adopt pseudoaxial orientations. When protecting groups do not contain an aromatic ring, the sterochemical outcome is dictated by stereoelectronic factors established by the Woerpel's model. Based on these findings, a concise total synthesis of the natural product (+)-varitriol and of two diastereoisomers was acomplished.

Stereoselective C-glycosidation of D-fucose derivatives directed by the protective groups.

Stereoselectivity in the C-glycosidation of lactones derived from D-fucose by following Kishi's method, which involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with Woerpel's model. On the other hand, their benzylated congeners produce the 1,3-cis products (ß anomer) as the major diastereoisomers. The latter results suggest an abnormal behavior during the stereoselective nucleophilic substitution at the anomeric position of the benzylated lactones.

A flexible approach for the preparation of substituted benzazepines: application to the synthesis of tolvaptan.

A practical preparation of benzazepine derivatives using a series of radical and ionic reactions is reported. This approach was applied to the synthesis of tolvaptan, a very promising vasopressin V2 receptor antagonist currently in clinical trials.

Model studies towards the synthesis of gilvocarcin M.

In model studies towards the synthesis of gilvocarcin M, a convergent, xanthate-based free-radical strategy was tested in order to construct the key aromatic ring attached to the sugar unit.

Synthesis of substituted naphthalenes from alpha-tetralones generated by a xanthate radical addition-cyclisation sequence.

A simple, highly efficient and cheap synthesis of substituted naphthalenes is reported. These aromatic compounds can be easily prepared in acidic or basic conditions from [small alpha]-tetralones, obtained by a xanthate-mediated addition-cyclisation sequence.