Utilizing the nitrogen-substituted donor-acceptor cyclopropane, enantiospecific total syntheses of (−)-hyacinthacine A₁⋅HCl and (+)-hyacinthacine A₁⋅HCl were achieved. The key reactions were highly stereo- and regioselective intramolecular cyclopropanation with rhodium(II) acetate and regioselective ring opening of nitrogen-substituted D−A cyclopropanes.

Abstract

A concise and efficient enantiospecific total synthesis of (−)-hyacinthacine A₁ and (+)-hyacinthacine A₁ was achieved from commercially available starting material L-pyroglutamic acid and D-glutamic acid, respectively. For the synthesis of this trihydroxylated pyrrolizidine ring, we employed the nitrogen-substituted donor-acceptor cyclopropane as a key intermediate. The synthetic approach relies on two crucial steps, highly stereo- and regioselective intramolecular cyclopropanation with Rh₂(OAc)₄ and regioselective ring opening of a nitrogen-substituted donor-acceptor cyclopropane.

Mn-mediated hydroxyphosphonylation of α-CF₃-styrenes with H-phosphonates and transition-metal-free hydroxyphosphinylation of α-CF₃-styrenes with H-phosphine oxides with the assistance of air were developed. A variety of β-hydroxy-β-CF₃-phosphonates and β-hydroxy-β-CF₃-phosphine oxides were synthesized in moderate to good yields.

Abstract

Efficient synthesis of β-hydroxy-β-CF₃-phosphonates and β-hydroxy-β-CF₃-phosphine oxides by Mn-mediated or transition-metal-free hydroxyphosphorylation of α-trifluoromethy)styrenes with H-phosphonates or H-phosphine oxides with the assistance of air, respectively, was described.

Previously, 6,6-dimethoxy-6,7-dihydrobenzocyclohepten-5-ones (“ketoketals”) gained by ring-closing metatheses (“RCMs”) gave 6-hydroxybenzocyclohepten-5-ones (“benzotropolones”) by hydrolyses with 10 equiv. of hot TsOH. Now, an RCM-based ketoketal allowed to reach the benzotropolone aurantricholone by total synthesis for the second time and to avoid a forcing hydrolysis. Another key to success was establishing the pulvinone(−like) motifs by our recently developed Suzuki strategy.

Abstract

Our first total synthesis of aurantricholone established its benzotropolone core by the ring-enlargement of a tetralone. Here we describe another total synthesis of aurantricholone. It reaches the benzotropolone core from a known olefin metathesis product via an equally known dibromide, both of which contain a ketoketal moiety. The next transformation - step 9 overall - engaged this motif in a β-elimination of ROH rather than in a hydrolysis under the forcing acidic conditions indispensable in all prior benzotropolone preparations from such an intermediate. In step 10, the C _sp2−Br bonds of the elimination product underwent two doubly Z-selective Suzuki couplings with a boronylated O-methyl 4-methylidenetetronate. This gave penta(O-methyl)aurantricholone. Its NMR shifts matched essentially those of a derivative of natural aurantricholone by Steglich et al. Three O−Me bonds were cleaved with BBr₃/CH₂Cl₂ (step 11) and two O−Me bonds with LiBr/DMF (step 12). A 1 : 3 co-crystal of aurantricholone and DMSO allowed for an X-ray structure analysis.

Reaction of 2,5-dibromothiophene dioxide with two equivalents of tetracyclone yields a heptaphenyl triphenylene, presumably by double Diels-Alder addition followed by fragmentation and rearrangement of the resulting radicals.

Abstract

In attempts to make octaphenyldibenzofuran (7) and octaphenyldibenzothiophene (8), 2,5-dibromofuran (4) and 2,5-dibromothiophene (5), respectively, were heated with tetracyclone (2) under forcing conditions, but only single addition products, such as 2-bromo-4,5,6,7-tetraphenylbenzofuran (10) and 2-bromo-4,5,6,7-tetraphenylbenzothiophene (12) were observed. However, when 2,5-dibromothiophene-1,1-dioxide (6) was heated with tetracyclone, the chief product was 1,2,3,4,6,7,8-heptaphenyltriphenylene (14). Similarly, when compound 6 was heated with acecyclone (15), the product was 11,18,20-triphenyldiacenaphtho[a,h]triphenylene (16). Both 14 and 16 have been characterized by X-ray crystallography. They are proposed to form from double Diels-Alder addition products of the cyclopentadienones by extrusion of sulfur dioxide and rearrangement of the resulting radicals.

A direct protocol for the facile construction of axially chiral iodobenzocarbazole derivatives via the catalytic asymmetric iodocyclization of indole moiety linked alkynes, using stereogenic-at-cobalt(III)-complex as the catalyst, has been developed. A range of versatile axially chiral iodobenzocarbazoles were obtained with up to 98 % ee under mild conditions.

Abstract

A new synthetic approach to novel axially chiral iodobenzocarbazole derivatives based on the highly enantioselective intramolecular iodoarylation of linked alkyne-indole systems was developed by using the versatile chiral catalyst, stereogenic-at-cobalt(III)-complex, through an axially chiral iodinated vinylidene o-quinone methide (IVQM) intermediate. This protocol provides 21 examples in excellent yields with good to high enantioselectivities (up to 96 % yield, 98 % ee). Furthermore, the introduced iodine atoms can easily be converted into other functional groups.

In this work, a photon- and metal-free approach for the radical fluorination of aliphatic oxalate-activated alcohols is reported.

Abstract

We present a photon- and metal-free approach for the radical fluorination of aliphatic oxalate-activated alcohols. The method relies on the spontaneous generation of the N-(chloromethyl)triethylenediamine radical dication, a potent single electron oxidant, from Selectfluor and 4-(dimethylamino)pyridine. The protocol is easily scalable and provides the desired fluorinated products within only a few minutes reaction time.

A mild and convenient synthesis of 3,4-unsubstituted isoquinolones has been achieved from N-methoxybenzamides and vinylene carbonate as an acetylene surrogate with a versatile rhodium(III) catalyst. The reaction proceeded at room temperature in biomass derived ethanol solvent. This protocol avoids the use of stoichiometric external oxidant, as the vinylene carbonate served as the internal oxidant. The C‒H/N‒H activation and annulation manifold proceeded with broad substrate scope and excellent levels of regioselectivities. The preliminary mechanistic studies suggest facile and reversible chelation-assisted C‒H rhodation. Diversification of 3,4-unsubstituted isoquinolones provide access to 4-substituted isoquinolones and 3,4-unsubstituted isoquinolines, which are complementary to the previously reported protocols.

A cross-electrophile coupling reaction of gem-difluoroalkenyl tosylate with α-CF₃ benzyl tosylate is presented. This protocol is the first example of cross-electrophile coupling between two different tosylates by Pd/Ni cooperative catalysis.

Abstract

Cross-electrophile coupling reactions are efficient for the construction of carbon-carbon bonds under relatively mild conditions, and hence widely used for making new molecules. Among various electrophiles, the cross-electrophile coupling reaction between two different tosylates has been rarely studied. Herein, we present a cross-electrophile coupling of gem-difluoroalkenyl tosylate (C(sp²)−OTs) and α-CF₃ benzyl tosylate (C(sp³)−OTs) by nickel/palladium cooperative catalysis. Mechanistic investigation indicated that the activation of C(sp²)−OTs bond and C(sp³)−OTs bond was facilitated by nickel and palladium respectively.

Asymmetric hydrofunctionalization of alkenes represents a powerful method to obtain valuable enantioenriched molecules from cheap and readily available materials. In this review, the recent advances in Palladium catalyzed asymmetric hydrofunctionalization of alkenes covering mainly contributions over the past decade are summarized. The remained challenges and opportunities in this field are also discussed.

Abstract

Palladium-catalyzed asymmetric hydrofunctionalization of alkenes is one of the most powerful and straightforward methods to forge a new C−H bond and a new C−X (X=C, N, O, F, Si etc) bond, which provides an efficient way to obtain valuable enantioenriched molecules from cheap and readily available feedstocks. Catalytic asymmetric hydrofunctionalization of simple alkenes is challenging but still highly sought after. This review will mainly focus on the recent advances in Palladium catalyzed asymmetric hydrofunctionalization of alkenes over the past decade, including hydroamination, hydrooxygenation, hydrofluorination, hydrosilylation, hydroarylation, hydroalkenylation and hydrocarbonylation.

The synthesis of densely functionalised spirocyclic products through a radical dearomative spirocyclisation chain mechanism is described. The spirocyclic products were converted into other spirocyclic scaffolds through a two-step ring expansion sequence.

Abstract

The dearomative spirocyclisation of benzisoxazoles through a radical chain mechanism is described. Densely functionalised spirocycles were prepared in high yields by reacting benzisoxazole-tethered ynones with aryl thiols in 1,2-dichloroethane (DCE) at 60 °C. The identification of stabilising three-electron interactions was key to the development of this new radical cascade reaction. The obtained spirocyclic products were converted into other spirocyclic scaffolds through a two-step hydrogenolysis-cyclisation sequence.