Cross-coupling Sequence Research Articles

Direct C-2 Arylation of Alkyl 4-Thiazolecarboxylates: New Insights in Synthesis of Heterocyclic Core of Thiopeptide Antibiotics

The Pd(0)-catalyzed regioselective C-2 (hetero)arylation of tert-butyl 4-thiazolecarboxylate with a broad (hetero)aryl halide is reported, including the direct coupling of pyridinyl halides. The process has allowed the preparation of valuable 2-pyridynyl-4-thiazolecarboxylates which are components of the complex heterocyclic core of thiopeptides antibiotics. As a first application, a synthesis of a tert-butyl sulfomycinamate thio-analogue from tert-butyl 4-thiazolecarboxylate is here described through a three-step direct pyridinylation, halogenation, and Stille cross-coupling sequence.

Practical synthesis of pinacolborane for one-pot synthesis of unsymmetrical biaryls via aromatic C–H borylation–cross-coupling sequence

A method for practical preparation of pinacolborane from borane-diethylaniline and pinacol was newly developed. Aromatic C–H borylation of arenes with pinacolborane or bis(pinacolato)diboron catalyzed by 1/2[Ir(OMe)(COD)] 2-(4,4′-di- tert-butyl-2,2′-bipyridine) at 25 °C in hexane to give arylboronic esters was directly followed by cross-coupling with aromatic bromides at 60 °C in the presence of PdCl 2(dppf) (3.0 mol %) and K 3PO 4 in DMF. This one-pot, two-step procedure provided a variety of unsymmetrical biaryls in high yields.

A New Class of Iridium Complexes Suitable for Stepwise Incorporation into Linear Assemblies: Synthesis, Electrochemistry, and Luminescence

A new family of cationic iridium(III) complexes is reported that contain two cyclometalating terdentate ligands. The complex [Ir(N--C--N-dpyx)(N--N--C-phbpy)]+ (1) contains one N--C--N-coordinating ligand, cyclometalating through the central phenyl ring, and one N--N--C-coordinated ligand, cyclometalated at the peripheral phenyl ring [dpyxH = 1,3-di(2-pyridyl)-4,6-dimethylbenzene; phbpyH = 6-phenyl-2,2'-bipyridine]. This binding mode dictates a mutually cis arrangement of the cyclometalated carbon atoms: the complexes are thus bis-terdentate analogues of the well-known [Ir(N--C-ppy)2(N--N-bpy)]+ family of complexes, which similarly contain a cis-C2N4 coordination environment. The dpyx ligand can be brominated regioselectively at the carbon atom para to the metal under mild conditions. Starting from a modified complex, [Ir(N--C--N-dpyx)(N--N--C-mtbpy-phi-Br)]+ (2), which incorporates a pendent bromophenyl group, a sequential cross-coupling-bromination-cross-coupling strategy can be applied for the stepwise introduction of aryl groups into the ligands, using in situ palladium-catalyzed Suzuki reactions with arylboronic acids [mtbpyH-phi-Br = 4-(p-bromophenyl)-6-(m-tolyl)bipyridine]. Dimetallic complexes 6 and 7 have similarly been prepared by a palladium-catalyzed reaction of complex 2 with 1,4-benzenediboronic acid and 4,4'-biphenyldiboronic acid, respectively. All five monometallic complexes and both dimetallic systems are luminescent in solution, emitting around 630 nm in MeCN at 298 K, with quantum yields in the range of 0.02-0.06, superior to [Ir(ppy)2(bpy)]+. The luminescence, electrochemistry, and singlet-oxygen-sensitizing abilities of the new family of complexes are discussed in the context of the tris-bidentate analogues and related bis-terdentate compounds that contain a trans arrangement of cyclometalated carbon atoms.

Total synthesis of (−)-spirangien A and its methyl ester

The first total synthesis of (-)-spirangien A, a cytotoxic and antifungal polyketide of myxobacterial origin, is reported; this exploits a Stork-Wittig olefination and double Stille cross-coupling sequence to install the sensitive pentaene side chain onto a fully elaborated spiroacetal core, leading initially to the methyl ester of spirangien A.

Convenient Synthesis of Photochromic Symmetrical or Unsymmetrical Bis(heteroaryl)maleimides via the Suzuki—Miyaura Cross‐Coupling Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Origin of Regioselectivity in Palladium-Catalyzed Cross-Coupling Reactions of Polyhalogenated Heterocycles

Sequential cross-coupling on multihalogenated heterocycles is a particularly attractive strategy for the divergent synthesis of polysubstituted heterocycles, but the factors that govern the regioselectivity are not well understood. The present study shows that the selectivity in palladium-catalyzed cross-coupling reactions of heterocycles bearing multiple identical halogens is determined by both the energy to distort the carbon halogen bond to the transition-state geometry (related to BDE) and the interaction of the heterocycle π* (LUMO) and PdL2 HOMO.

Convenient synthesis of photochromic symmetrical or unsymmetrical bis(heteroaryl)maleimides via the Suzuki–Miyaura cross-coupling reaction

A general method for the synthesis of symmetrical or unsymmetrical bis(heteroaryl)maleimides by a one-pot procedure involving Suzuki–Miyaura cross-coupling sequence was developed on the basis of the reaction of 3,4-diiodo-1-benzyl-1 H-pyrrole-2,5-dione with cyclic boronate esters using PdCl 2(dppf) as the catalyst. Photochromic properties of the products were examined.

DirectedorthoMetalation−Boronation and Suzuki−Miyaura Cross Coupling of Pyridine Derivatives: A One-Pot Protocol to Substituted Azabiaryls

A general method for the synthesis of azabiaryls 19a-t by a one-pot procedure involving a Directed ortho metalation (DoM)-boronation-Suzuki-Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides 15a-c, chloro-, fluoro-, and O-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table 2). The method has an advantage in that it avoids the recognized difficult isolation of pyridyl boronic acids and their instability toward deboronation. The efficient synthesis of hydroxypicolinamides 12-14 (Scheme 3) by a one-pot metalation-boronation-oxidation sequence with the LDA-B(OiPr)3 in situ procedure that avoids self-condensation of incipient ortho-metalated species (Scheme 2) is delineated. The conversion of azabiaryls 19b,e,h,l into azafluorenones 20b,e,h,l by a directed remote metalation protocol is demonstrated (Table 3). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure 1).

Rhodium‐Catalyzed Multicomponent‐Coupling Reactions Involving a Carborhodation—Cross‐Coupling Sequence.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

New Synthetic Applications of Indium Organometallics in Cross‐Coupling Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New Synthetic Applications of Indium Organometallics in Cross-Coupling Reactions

The use of indium organometallics in multifold and sequential cross-coupling reactions is reported. Triorganoindium reagents (R 3 In) react, under palladium catalysis, with oligohaloarenes affording the multiple cross-coupling products in a single operation. In the reaction, the three organic groups (alkyl, aryl, alkenyl or alkynyl) attached to indium are efficiently transferred to the electrophile, with only a slight excess of organometallic reagent. We demonstrate that indium organometallics are useful reagents for sequential cross-coupling reactions. This reaction illustrates the high chemoselectivity of R 3 In. 1 Introduction 2 Results and Discussion 2.1 Multifold Cross-Coupling Reactions 2.2 Sequential Cross-Coupling Reactions 3 Conclusion

Combined Directed ortho and Remote Metalation—Cross‐Coupling Strategies. General Method for Benzo[a]carbazoles and the Synthesis of an Unnamed Indolo[2,3‐a]carbazole Alkaloid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective synthesis of (E)‐α‐aryltellurenylvinylstannanes and their application in the synthesis of stereodefined trisubstituted alkenes

Abstract(E)‐α‐Aryltellurenylvinylstannanes have been synthesized stereoselectively via the hydrozirconation of alkynylstannanes, followed by the reactions with aryltellurenyl iodides. (E)‐α‐Aryltellurenylvinylstannanes can undergo sequential cross coupling reactions with both electrophiles and nucleophiles in the presence of transition metal complexes to form two carbon‐carbon bonds in the same olefinic carbon leading to trisubstituted alkenes stereoselectively.

(E)‐α‐Bromovinylselenides as Convenient Precursors for Stereoselective Synthesis of Trisubstituted Alkenes

AbstractBased on the different reactivity of selanyl and bromo groups, (E)‐α‐bromovinylselenides can undergo sequential cross coupling reactions with nucleophiles in the presence of transition metal complexes to form two carbon‐carbon bonds in the same olefinic carbon leading to trisubstituted alkenes stereoselectively in good yields.

Multifold and Sequential Cross‐Coupling Reactions with Indium Organometallics.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rapid route to 3,4-substituted indoles via a directed ortho metalation-retro-Mannich sequence.

[reaction: see text] In the presence of NXS (X = Br, I, Cl), gramine derivatives 1, derived by combined directed ortho metalation (DoM)-cross-coupling sequences, rapidly undergo retro-Mannich fragmentation (2) to afford 3-halo indoles 3 in 37-88% yields. A conceptually new methodology to diverse 3,4-substituted indoles (10, 11, 13) is thereby introduced.

Sequential ring-closing metathesis and silicon-assisted cross-coupling reactions: stereocontrolled synthesis of highly substituted unsaturated alcohols.

A sequential ring-closing metathesis/silicon-assisted cross-coupling sequence has been developed. Alkenyldimethylsilyl ethers of omega-unsaturated alcohols undergo facile ring closure with Schrock's catalyst to afford five-, six-, and seven-membered cycloalkenylsiloxanes bearing substituents on both alkenyl carbons. These siloxanes were highly effective coupling partners with various aryl and alkenyl halides and in the presence of Pd(0) afforded styrenes and dienes in high yield and specificity and with good functional group compatibility.

Approach toward the total synthesis of orevactaene. Part 1: Assembly of the contiguous trisubstituted olefin component

An approach to the conjugated polyene chain component of orevactaene is reported. A modular approach has been devised to link the two stereocentre-containing ends of the structure together via a tri-substituted olefin-template. Key to the success of this approach is an efficient ‘one pot’ lithium/halogen exchange, boron/lithium exchange, borate ester saponification, and cross-coupling sequence to provide two contiguous trisubstituted olefins with absolute stereo- and regiocontrol in excellent overall yield. These results have paved the way for a parallel synthesis approach to prepare all 16 possible stereoisomers of orevactaene so that the relative and absolute stereochemistry of this compound can be determined.

Carbon networks based on dehydrobenzoannulenes. 3. Synthesis of graphyne substructures

This Letter describes the synthesis of the first macrobicyclic subunits of the hypothetical all-carbon network graphyne. Key to synthetic success is an intramolecular Sonogashira cross-coupling sequence.

Polymer-supported synthesis of regioregular head-to-tail-coupled Oligo(3-arylthiophene)s utilizing a traceless silyl linker

The solid-phase synthesis of regioregular head-to-tail-coupled oligo(3-arylthiophene)s has been achieved in high yield and purity by using a traceless silyl ether linkage. In the first step, the solution-phase synthesis of this class of conjugated oligomers was investigated. Benzyl alcohol was chosen to serve as a mimic for the anchoring group of the hydroxymethyl-substituted polystyrene matrix. The development of a novel regioselective iodination process for silyl-protected thiophenes faciliates the successful application of the solution-phase protocol to the solid phase. Satisfactory loading was obtained by reaction of chlorosilyl-functionalized 3-arylthiophene with hydroxymethyl polystyrene in the presence of imidazole. The suitability of the following iterative halogenation and Suzuki cross-coupling sequence is illustrated by the preparation of a quater(3-arylthiophene), the first regioregular head-to-tail-coupled oligothiophene that is synthesized on solid support. Removal of the conjugated oligomers from the solid support could be effectively achieved by treatment with tetrabutylammonium fluoride.