Visible-Light-Mediated Ru-Catalyzed Synthesis of 3-(Arylsulfonyl)but-3-enals via Coupling of α-Allenols with Diazonium Salts and Sulfur Dioxide.

The first coupling of α-allenols, sulfur dioxide, and arenediazonium salts is presented. The three-component reaction which is promoted by visible light can be easily accomplished using DABSO as a sulfur dioxide surrogate in the presence of a photoredox catalyst. In this manner, a broad range of electron-rich and electron-deficient aryl substituents are well accommodated in the sulfonylation-rearrangement cascade to afford the 2,2-disubstituted 3-(arylsulfonyl)but-3-enals in reasonable yields. Based on control experiments, a radical mechanism which does imply 1,2-aryl migration has been proposed.

Transition metal-free cyclobutene rearrangement in fused naphthalen-1-ones: controlled access to functionalized quinones.

The controlled synthesis of 1,4-naphthoquinones and tetraphene-7,12-diones, which bear the ABCD-ring of landomycins, has been accomplished directly through oxidative rearrangement of common stable precursors, namely, previously non-isolable cyclobuta[a]naphthalen-4(2H)-ones.

Gold-Catalyzed Divergent Ring-Closing Modes of Indole-Tethered Amino Allenynes.

Indole-tethered amino allenynes were chemodivergently cyclized for the controlled preparation of fused polycyclic indoles using gold catalysis. Double cyclization of terminal allenynes afforded hexacyclic 15 H-indolo[1,2,3-de]quinolino[3,2,1-ij]quinoxalines, in which allenynes bearing a substituted alkyne at the terminal end generated 12,13-dihydro-7 H-indolo[3,2-c]acridines, which are 5-membered cyclized adducts. Density functional theory calculations were performed to shed light on this difference in reactivity.

De Novo Synthesis of α-Hydroxy Ketones by Gallic Acid-Promoted Aerobic Coupling of Terminal Alkynes with Diazonium Salts.

An unprecedented metal-free direct preparation of unprotected α-hydroxy ketones from terminal alkynes under mild conditions with diazonium salts as the arene source and without the requirement of irradiation is described. The process is general and fully compatible with a wide variety of substitution in both reactants. Experimental and computational evidence strongly suggest the involvement of radical species in the transformation.

An Alternative to Precious Metals: Hg(ClO4)2·3H2O as a Cheap and Water-Tolerant Catalyst for the Cycloisomerization of Allenols.

Hg(ClO4)2·3H2O, a cheap, water-tolerant, and stable salt, catalyzes the cycloisomerization reaction or α-allenols to 2,5-dihydrofurans in an efficient and selective manner. The reaction is general and can be applied to differently functionalized substrates, including alkyl-substituted, aryl-substituted, enantiopure, and tertiary allenols. In addition, density functional theory (DFT) calculations were performed to obtain insight into various aspects of the controlled reactivity of α-allenols under mercury catalysis. They suggest a dual activation of the allenol by the Hg complex that drives the reaction to the chemoselective formation of 2,5-dihydrofurans.

Gallium-catalyzed domino arylation/oxycyclization of allenes with phenols.

The synthesis of dihydrobenzofuran-appended oxindoles has been accomplished taking advantage of an unprecedented reaction between allenols and phenols under metal catalysis.

Metal-catalyzed rearrangements of 3-allenyl 3-hydroxyindolin-2-ones in the presence of halogenated reagents.

The reactions of 3-allenyl 3-hydroxyoxindoles with a variety of halogenated reagents in the presence of catalytic amounts of precious metal salts were explored. Both, rearrangement and oxycyclization reactions to give 4-(1-halovinyl)-quinolinediones or spirocyclic halooxindoles, respectively, are competitive pathways. The kind of functionalization is substrate and reaction conditions dependent.

Direct FeX3-based stereocontrolled access to (Z)-3-alkenyl-oxindoles from allenols.

Iron trihalides (FeCl(3) and FeBr(3)) smoothly promote the halogenation/rearrangement of 2-indolinone-tethered allenols to efficiently afford 3-halodienyl-oxindoles with good yield and total selectivity. Also, 2-halo-1,3-dienes are synthetically interesting building blocks for the preparation of functionalized 3-alkenyl-oxindoles through a Suzuki-Miyaura reaction.

Ring enlargement versus selenoetherification on the reaction of allenyl oxindoles with selenenylating reagents.

Lactam-tethered allenols, readily prepared from α-oxolactams, were used as starting materials for divergent reactivity with selenenylating reagents. Either oxycyclization (spirocyclic selenolactams) or ring expansion (selenoquinolones) can be achieved through the choice of both reagents and substrates. The biological activity of some of the synthesized heterocycles has additionally been evaluated in four human cancer cell lines.

Controlled rearrangement of lactam-tethered allenols with brominating reagents: a combined experimental and theoretical study on α- versus ß-keto lactam formation.

N-Bromosuccinimide (NBS) smoothly promotes the ring expansion of lactam-tethered allenols to efficiently afford cyclic α- or ß-ketoamides with good yields and high chemo-, regio-, and diastereoselectivity, through controlled C-C bond cleavage of the ß- or γ-lactam nucleus. Interestingly, in contrast to the rearrangement reactions of 2-azetidinone-tethered allenols, which lead to the corresponding tetramic acid derivatives (ß-keto lactam adducts) as the sole products, the reactions of 2-indolinone-tethered allenols under similar conditions give quinoline-2,3-diones (α-keto lactam adducts) as the exclusive or major products. To rationalize the experimental observations, theoretical studies have been performed.

Stereoselective NaN3-catalyzed halonitroaldol-type reaction of azetidine-2,3-diones in aqueous media.

Azetidine-2,3-diones (alpha-oxo-beta-lactams) and bromonitromethane undergo coupling in aqueous media in the presence of catalytic amounts of sodium azide. The stereoselectivity of the process was generally good, proceeding with reasonable anti : syn ratios under substrate control. On this basis, a simple and fast protocol for the synthesis of the potentially bioactive 3-substituted 3-hydroxy-beta-lactam moiety has been developed. Besides, 2-azetidinone-tethered 1-halo-1-nitroalkan-2-ols are quite useful building blocks; for example, reactions of the above nitrobromohydrins provided spiranic and fused bicyclic-beta-lactams.

Synthesis of novel enantiopure 4-hydroxypipecolic acid derivatives with a bicyclic beta-lactam structure from a common 3-azido-4-oxoazetidine-2-carbaldehyde precursor.

Two different stereocontrolled accesses to new 4-hydroxypipecolic acid analogues with a bicyclic beta-lactam structure have been developed by using intramolecular reductive amination or allenic hydroamination reactions in 2-azetidinone-tethered azides. The access to the cyclization precursors was achieved from 3-azido-4-oxoazetidine-2-carbaldehyde via metal-mediated carbonyl-allenylation in aqueous environment or by organocatalytic direct aldol reaction. The tin hydride-promoted cyclization of the 2-azetidinone-tethered azidoallene is totally regioselective for the central allenic carbon providing a fused piperidine.

Proline-catalyzed diastereoselective direct aldol reaction between 4-oxoazetidine-2-carbaldehydes and ketones.

The reaction of enantiopure 4-oxoazetidine-2-carbaldehydes with unmodified ketones was catalyzed by L-proline as well as by D-proline, to give the corresponding gamma-amino-beta-hydroxy ketones with good yields and diastereoselectivities. The obtained results implied that (2R,3R)-4-oxoazetidine-2-carbaldehydes and L-proline are a matched pair for diastereoselective induction.

Biocatalytic approaches toward the synthesis of both enantiomers of trans-cyclopentane-1,2-diamine.

[reaction: see text] A lipase-catalyzed double monoaminolysis of dimethyl malonate by (+/-)-trans-cyclopentane-1,2-diamine allows the sequential resolution of the latter compound, affording an enantiopure bis(amidoester), which is subsequently transformed into an optically active polyamine. As an alternative, both enantiomers of the diamine can be obtained from enantiopure (+)- or (-)-2-aminocyclopentanol, prepared by enzymatic resolution.