Shaoguang Zhang

Efficient One-Pot Synthesis of N-Containing Heterocycles by Multicomponent Coupling of Silicon-Tethered Diynes, Nitriles, and Isocyanides through Intramolecular Cyclization of IminoacylZr Intermediates

An efficient multicomponent synthesis of 5-azaindoles and dihydropyrrolo[3,2-c]azepines was achieved by zirconocene-mediated coupling of silicon-tethered diynes, nitriles, and isocyanides. The synthesis, structures, and intramolecular cyclization of mono- and bis(iminoacyl)--Zr intermediates were investigated to elucidate the reaction process. Upon hydrolysis, the isolated mono(iminoacyl)--Zr intermediates underwent intramolecular cyclization to afford tetrasubstituted 5-azaindoles, whereas intramolecular cyclization of bis(iminoacyl)--Zr intermediates led to the formation of dihydropyrrolo[3,2-c]azepines. The structure of a bis(iminoacyl)--Zr intermediate, formed through insertion of two molecules of CyNC into the Zr--C bond, and structures of two dihydropyrrolo[3,2-c]azepines were characterized by single-crystal X-ray structural analysis.

Cleavage and reorganization of Zr-C/Si-C bonds leading to Zr/Si-N organometallic and heterocyclic compounds.

The t-BuCN-stabilized zirconacyclopropene-azasilacyclopentadiene complexes 2 are generated in situ in high yields from the Si-tethered diynes, Cp(2)Zr(II) species, and 2 equiv of t-BuCN via a coordination-induced Zr-C/Si-C bond cleavage and reorganization. Complexes 2 have been demonstrated to be synthetically very useful. A variety of novel Zr/Si organo-bimetallic compounds and Si/N heterocyclic compounds, such as azasilacyclopentadienes, azasilacyclohexadienes, and allenylazazirconacycles, are obtained in high yields when complexes 2 are treated with ketones, carbodiimides, alkynes, elemental sulfur (S(8)), acid chlorides, or nitriles. In this chemistry, t-BuCN behaves as both an initiator and a brake/release handle to initiate and control the reaction process.

One-Pot Synthesis of Pyrrolo[3,2-d]pyridazines and Pyrrole-2,3-diones via Zirconocene-Mediated Four-Component Coupling of Si-Tethered Diyne, Nitriles, and Azide

A one-pot synthesis of pyrrolo[3,2-d]pyridazine derivatives via zirconocene-mediated four-component coupling of one Si-tethered diyne, two nitriles, and one azide is reported. When TMSN(3) was used, pyrrole-2,3-diones were formed in good yields. Further condensation of these highly functionalized pyrrole-2,3-diones with hydrazine and hydroxylamine afforded useful pyrrole-fused heterocycles.

Iterative Dianion Relay Along the Ring: Formation of gem-Bis(trimethylsilyl) Cyclopentenones from 2,5-Bis(trimethylsilyl) Oxy-cyclopentadienyl Dianions and Acid Chlorides

Anionic migration of silyl groups has become one of the most useful protocols for synthetic chemistry. The intramolecular 1,n-anionic migration of a silyl group from a carbon atom to an oxygen atom is generally referred to as Brook rearrangement (Scheme 1) and the reverse process (from an oxygen atom to a carbon atom) is called retroBrook rearrangement (or West rearrangement). Both the Brook rearrangement and the retro-Brook rearrangement are currently widely applied in organic synthesis. As illustrated in Scheme 1, a recent yet very useful strategy applying anionic migrations of silyl groups is the anion relay chemistry (ARC) developed by Smith III et al. The ARC, a multi-component linchpin protocol, has been demonstrated to be useful for high-efficient and facile synthesis of structurally complex scaffolds. To further apply to synthetic chemistry the useful protocol based on the anionic migration of silyl groups, the design and development of new linchpins is currently of great demand and represents a great challenge. In recent years, we have demonstrated that the reaction of 1,4-dilithio-1,3-butadienes 1 with CO leads to the formation of substituted oxy-cyclopentadienyl dianion intermediates 2 (OCp dianions; Cp =cyclopentadienyl). Because of the concomitance of the Cp anion, the exocyclic oxyanion, and those multi-reactive sites, the OCp dianions 2 are structurally very unique and can be used for novel reaction chemistry. During the course of our continuous study on their reaction chemistry, we realized that those OCp diACHTUNGTRENNUNGanions substituted with trimethylsilyl groups could be used as a new type of dianionic relay linchpins. Iterative anion relay, in which one silyl group was shifted twice along the Cp ring with the exocyclic oxyanion as the posthouse, was observed the first time in anionic migration of silyl groups (Scheme 1). Interesting and otherwise unavailable compounds have been thus generated. Herein, we report our preliminary results. 1,4-Dilithio-1,4-bis(trimethylsilyl)-1,3-butadienes (dilithio reagents) 1 can be readily generated in quantitative yields from their corresponding 1,4-diiodobutadienes and tBuLi. Treatment of dilithio reagents 1 with CO led to the formation of OCp dianions 2. When the reaction mixture containing 2 a in diethyl ether was further treated with two equivalents of ArCOCl possessing electron-donating groups on Ar, such as 4-methylbenzoyl chloride, a double-acylation product was obtained. However, surprisingly, when one equivalent of PhCOCl was used, the 3-cyclopentenone derivative 5 aa containing a stable enol moiety was obtained in 74 % [a] H. Li, Dr. L. Liu, Z. Wang, F. Zhao, S. Zhang, Prof. Dr. W.-X. Zhang, Prof. Dr. Z. Xi Beijing National Laboratory for Molecular Sciences (BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry Peking University, Beijing 100871 (P.R. China) Fax: (+86) 10-62751708 E-mail : zfxi@pku.edu.cn [b] Prof. Dr. Z. Xi State Key Laboratory of Organometallic Chemistry SIOC, CAS Shanghai 200032 (P.R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100830. Scheme 1. Modes of anionic migration of silyl groups. ASG=anion stabilizing group, LP = linchpin.

One‐Pot Selective Syntheses of 5‐Azaindoles through Zirconocene‐Mediated Multicomponent Reactions with Three Different Nitrile Components and One Alkyne Component

5-Azaindoles either with three different substituents at their 2-, 4-, and 6-positions or with two identical substituents at their 2- and 6-positions and a different one at the 4-position, were obtained in good to excellent isolated yields by a zirconocene-mediated multicomponent process. Each reaction involved four organic partners, comprising a Si-tethered diyne, one tBuCN component, and two (either different or identical) nitriles. All these four components were combined through the action of a Cp(2)Zr(II) species into a three-ring fused Zr/Si-containing organometallic complex in a perfectly chemo- and regioselective manner. This multicomponent reaction process consisted of three reaction steps, all of which were made clear through the isolation and characterization of their corresponding organometallic intermediates: the zirconacyclopropene-azasilacyclopentadienes 2, the allenyl-aza-zirconacycles 3, and the three-ring fused complexes 6. X-ray single-crystal structural analyses of two three-ring fused Zr/Si-containing intermediates and two 5-azaindoles unambiguously showed the positions of the different substituents and the regioselectivity. Iminopyrrole derivatives could be also highly selectively prepared from a Si-tethered diyne and two different nitriles.

Lewis acid catalyzed site-selective cycloadditions of 2,6-diazasemibullvalenes with isocyanides, azides, and diazo compounds for the synthesis of diaza- and triazabrexadiene derivatives.

The authors further expanded the scope of the reaction by employing lanthanum catalysis and azides to generate 19 additional products (51–96% yield).

Diazo compounds as electrophiles to react with 1,4-dilithio-1,3-dienes: efficient synthesis of 1-imino-pyrrole derivatives.

1-Imino-pyrrole and indole derivatives were synthesized in high yields from the reaction of diaryl diazomethanes with 1,4-dilithio-1,3-dienes. Diaryl diazomethanes reacted as electrophiles in this reaction. An unprecedented Zn-complex was formed via transmetalation of the above reaction intermediate with ZnCl2 and was structurally characterized. The trans-μ2-η(1):η(1) coordination mode in the solid state for this azaallylzinc compound was observed.

Oxidation of C–H bonds to CO bonds by O2 only or N-oxides and DMSO: synthesis of Δ1-bipyrrolinones and pyrrolino[3,2-b]pyrrolinones from 2,6-diazasemibullvalenes

2,6-Diazasemibullvalenes (NSBVs) readily reacted with oxygen under mild conditions, affording Δ(1)-bipyrrolinones via C-N bond cleavage and C-H bond oxidation. Pyrrolino[3,2-b]pyrrolinone derivatives were efficiently generated when NSBVs were treated with N-oxides in the presence of Lewis acids. Δ(1)-Bipyrrolinones thus obtained could be readily transformed into other heterocycles.

Synthesis of semibullvalene derivatives via Co2(CO)8-mediated cyclodimerization of 1,4-dilithio-1,3-butadienes

Co2(CO)8-mediated cyclodimerization of 1,2,3,4-tetrasubstituted 1,4-dilithio-1,3-butadienes readily afforded octa-substituted semibullvalenes. The X-ray crystal structure of 1,2,5,6-tetraethyl-3,4,7,8-tetraphenyl semibullvalene was determined to show an unsymmetrical, localized structure, which is in sharp contrast with the C2 symmetrical structure of its tetramethyl analogue. In addition, this Co2(CO)8-mediated cyclodimerization was found to be dependent on the substitution pattern of 1,4-dilithio-1,3-butadienes. The 1,4-diphenyl dilithio compound gave its corresponding cyclooctatetraene derivative, while the dilithio reagent without substituents at its 1,4-positions afforded a cyclopentadienone [4 + 2] dimer.

Diastereoselective Nucleophilic Ring‐Opening Reactions of 2,6‐Diazasemibullvalenes for the Synthesis of Diverse Functionalized Δ1‐Bipyrroline Derivatives

Nucleophilic ring-opening reactions of 2,6-diazasemibullvalenes (NSBVs) were investigated. Different types of nucleophile (alcohols, phenols, thiols, carboxylic acids, water, enols, amines, indoles, metal-halide salts, sodium azide, organozinc compounds, lithium alkynethiolate, and sulfoxonium ylides) were used to afford diverse functionalized Δ(1) -bipyrroline derivatives in good yields with high regio- and diastereoselectivity. Most of the reactions featured milder conditions and higher reactivity relative to those for common aziridine derivatives, probably because of the rigid ring system and substitution patterns of NSBVs.