New Synthesis of α′‐Hydroxydienones

Herein, attempted oxidation of selected allenols with PCC affording α′‐hydroxydienones rather than simple oxidation products is described. The formation of the products observed is rationalized via a series of sigmatropic shifts, followed by hydrolysis.     

Highly Diastereo‐ and Enantioselective Silver‐Catalyzed Double [3+2] Cyclization of α‐Imino Esters with Isocyanoacetate

Presented herein is a new complexity‐generating method in which both functionalities of α‐imino esters undergo stereoselective cyclization with isocyanoacetates to produce directly linked oxazole‐imidazolines, which can be transformed into highly functionalized α,β‐diamino esters and imidazolinium salts in high diastereo‐ and enantiopurity.     

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

We report a simple, highly stereoselective synthesis of (+)‐(S)‐γ‐ionone and (‐)‐(2S,6R)‐cis‐γ‐irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au^I]‐catalyzed Meyer–Schuster‐like rearrangement. This required a careful investigation of the mechanism of the gold‐catalyzed reaction and a judicious selection of reaction conditions. In fact, it was found that the Meyer–Schuster reaction may compete with the oxy‐Cope rearrangement. Gold‐based catalytic systems can promote either reaction selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in combination with the silver salt AgSbF₆ in 100:1 butan‐2‐one/H₂O, proved to efficiently promote the Meyer–Schuster rearrangement of propargylic benzoates, whereas the digold catalyst [{Au(IPr)}₂(μ‐OH)][BF₄] in anhydrous dichloromethane selectively promoted the oxy‐Cope rearrangement of propargylic alcohols.     

Divergent Synthesis of Hydro‐γ‐Carbolines and Multisubstituted Indoles through Grob Fragmentation/Mannich Cyclization

A distinct strategy for the divergent synthesis of hydro‐γ‐carbolines and multisubstituted indoles is reported. The stereochemical outcomes and a control experiment indicate that the reactions likely proceed through Grob fragmentation/Mannich cyclization rather than a concerted aza‐pinacol rearrangement.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

Pd(II)‐Catalyzed Tandem Enantioselective Methylene C(sp3)−H Alkenylation–Aza‐Wacker Cyclization to Access β‐Stereogenic γ‐Lactams

Herein, we describe an unprecedented cascade reaction to β‐stereogenic γ‐lactams involving Pd(II)‐catalyzed enantioselective aliphatic methylene C(sp³)?H alkenylation–aza‐Wacker cyclization through syn‐aminopalladation. Readily available 3,3′‐substituted BINOLs are used as chiral ligands, providing the corresponding γ‐lactams with broad scope and high enantioselectivities (up to 98 % ee).     

Vicinal α,β‐Functionalizations of Amines: Cyclization Versus Dehydrogenative Hydrolysis

Direct vicinal α,β‐difunctionalization of tertiary cyclic amines is achieved in the presence of ruthenium or iridium transition‐metal complexes featuring phosphine‐sulfonate chelates. By varying the reaction conditions, α‐alkylated lactams were obtained by a formal dehydrogenative hydrolysis in which one molecule of hydrogen is generated from water.     

Expanding the Scope of Enantioselective FerroPHANE‐Promoted [3+2] Annulations with α,β‐Unsaturated Ketones

The planar chiral 2‐phospha[3]ferrocenophane I has been shown to be the first efficient nucleophilic organocatalyst for the enantioselective synthesis of cyclopentenylphosphonates, through [3+2] cyclizations between diethyl allenylphosphonate and α,β‐unsaturated ketones. The same catalyst has also been applied to the highly enantioselective [3+2] cyclizations of allenic esters with dibenzylideneacetone and analogous bis‐enones, leading to functionalised cyclopentenes with either monocyclic or spirocyclic structures (ee 84–95 %). It has been shown that the residual enone functions in the resulting cyclopentenes can be involved in subsequent cyclization steps to afford unprecedented C₂‐symmetric bis‐cyclopentenylketones. In order to provide insight into the behaviour of FerroPHANE I as a chiral catalyst in [3+2] cyclisations, the energetically most favoured isomers of the key phosphine‐allene adduct have been calculated by DFT methods. Factors likely to control the chiral induction process are highlighted.     

A C‐linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Manα(1,6)‐C‐ManαOPh

The effect of carbon is subtle but sweet : The flexible C‐linkage in the newly synthesised C‐glycosyl mimetic, Manα(1,6)‐C‐ManαOPh allows OH? π bonding, both in the gas phase and in aqueous solution. This interaction is absent in the O‐linked disaccharide (see figure).

     

Metal‐Catalyzed Cyclization of β‐ and γ‐Allenols Derived from D‐Glyceraldehyde—Synthesis of Enantiopure Dihydropyrans and Tetrahydrooxepines: An Experimental and Theoretical Study

Regiocontrolled metal‐catalyzed preparations of enantiopure dihydropyrans and tetrahydrooxepines have been synthesized starting from β‐ and γ‐allenols derived from D ‐glyceraldehyde. The Pd^II‐catalyzed cyclizative coupling reactions of β‐allenols 1 a and 1 b with allyl bromide effectively afforded enantiopure tetrafunctionalized dihydropyrans through a 6‐endo oxycyclization protocol, whereas the gold‐, platinum‐, and palladium‐mediated heterocyclization of γ‐allenol 2 furnished tetrahydrooxepines 13 – 16 through regioselective 7‐endo‐trig oxycyclization reactions. Moreover, density functional calculations were performed to predict the regioselectivity of the γ‐allenol cycloetherification to tetrahydrooxepines on the basis of both the tether nature and characteristics of the metals, and to gain an insight into the mechanism of the oxycyclization reactions.     

From Ynamides to Highly Substituted Benzo[b]furans: Gold(I)‐Catalyzed 5‐endo‐dig‐Cyclization/Rearrangement of Alkylic Oxonium Intermediates

A series of arylynamides with alkyloxy groups at the ortho position of the aryl group was prepared through a short alkylation/cross‐coupling/amidation sequence. The gold‐catalyzed conversion of these substrates combined both C? O and C? C formation steps, thus providing benzofurans with amine functionalities at the 2‐position and alkyl groups at the 3‐position. Cross‐over experiments showed that the alkyl‐migration step was an intermolecular process. X‐ray crystal‐structure analysis of two of the products supported our structural assignment. In some cases, the corresponding benzofurans without the alkyl group at the 3‐position were obtained as side‐products, which were formed through a competing protodeauration process.