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A regiocontrolled halogen dance reaction of 2,5-dibromopyrroles is described. An N , N -dimethylsulfamoyl group on the pyrrole nitrogen was especially effective for facilitating interconversion of the resulting 2,3- and 2,4-dibromopyrrolyllithiums, rendering the smooth halogen dance reaction. This method was applicable to the formal synthesis of atorvastatin.

A bottom-up synthesis of lamellarins G, J, L, and Z was achieved via one-pot halogen dance/Negishi coupling of a lithiated dibromopyrrole derivative. The easily accessible dibromopyrrole bearing an ester moiety underwent halogen dance smoothly at -78 °C within 10 min. The resultant α-pyrrolyllithium was transmetalated to the corresponding organozinc species, which was then coupled with an aryl iodide in the presence of catalytic palladium to provide the fully substituted pyrrole. Subsequent halogen-lithium exchange was performed to incorporate a boronate group exclusively at the β position proximal to the ester moiety. This synthetic intermediate allowed stepwise diarylation for the total synthesis of lamellarins G, J, L, and Z.

Multiply substituted pyrroles are found in medicines, natural products, and functional materials. A general method for introducing functionality on the pyrrole ring is thus required. Herein, a regiocontrolled halogen dance reaction and an in situ transmetalation of α-functionalized bromopyrroles are reported. Selective generation of the isomeric pyrrolylmetal species was achieved by using an ethyl ester or a phenyl group at the α-position of the pyrrole and by switching between the halogen dance reaction and in situ transmetalation. These reactions proceeded smoothly when an N , N -dimethylsulfamoyl group was attached to the pyrrole nitrogen atom, providing the corresponding products in 68% to quantitative yields on 1-mmol scale. This method was applicable to the formal synthesis of Kendine 91. [ABSTRACT FROM AUTHOR]

Lochmann–Schlosser base, a stoichiometric combination of nBuLi and KOtBu, is commonly used as a superbase for deprotonating a wide range of organic compounds. In the present study, we report that catalytic potassium hexamethyldisilazide (KHMDS) exhibits higher catalytic activity than KOtBu for successive bromine–metal exchanges. Accordingly, 1–10 mol% of KHMDS dramatically enhances halogen dance reactions to introduce various electrophiles to bromopyridine, bromoimidazole, bromothiophene, bromofuran, and bromobenzene derivatives with the bromo group translocated from the original position. A dual catalytic cycle is proposed to explain the ultrafast bromine transfer. [ABSTRACT FROM AUTHOR]

A total synthesis of lamellarins U and A3 is described. The synthesis features the interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation by using (TMP)MgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidide) as the base, was transmetalated to the corresponding organozinc species without causing the halogen dance reaction, which underwent a Negishi coupling to incorporate an aryl group onto the pyrrole ring. The arylated α,β-dibromopyrrole was then converted into lamellarins U and A3 through an α-selective halogen–magnesium exchange followed by carboxylation and subsequent palladium-mediated cyclization. The late-stage introduction of another aryl group was performed using a Kosugi–Migita–Stille coupling to provide lamellarins U and A3. [ABSTRACT FROM AUTHOR]

Recent developments in flow microreactor technology have allowed the use of transient organolithium compounds that cannot be realized in a batch reactor. However, trapping the transient aryllithiums in a "halogen dance" is still challenging. Herein is reported the trapping of such short‐lived azolyllithiums in a batch reactor by developing a finely tuned in situ zincation using zinc halide diamine complexes. The reaction rate is controlled by the appropriate choice of diamine ligand. The reaction is operationally simple and can be performed at 0 °C with high reproducibility on a multigram scale. This method was applicable to a wide range of brominated azoles allowing deprotonative functionalization, which was used for the concise divergent syntheses of both constitutional isomers of biologically active azoles. [ABSTRACT FROM AUTHOR]

Selective trapping of (4,5-dibromo-2-thienyl)lithium, known to undergo halogen dance, was achieved in a flow microreactor. This transient thienyllithium, generated by mixing 2,3-dibromothiophene and lithium diisopropylamide at –78 °C for 1.6 seconds, reacted with benzaldehyde. The reaction system is also applicable to other carbonyl compounds to afford the corresponding adducts in good yields. Moreover, the established conditions permit the conversion of 2,5-dibromothiophene into a mixture of the two constitutional isomers. The contrasting results are discussed on the basis of the reaction pathway. [ABSTRACT FROM AUTHOR]

One-pot halogen dance/Negishi cross-coupling of readily available 2,5-dibromothiophenes is described. A lithium diisopropylamide (LDA)-mediated halogen dance reaction resulted in the formation of thermodynamically stable α-lithiodibromothiophenes, which were transmetalated with ZnCl2 and subjected to Negishi cross-coupling to provide the corresponding arylated dibromothiophenes in one pot. The resultant β-bromo group was much less reactive than the remaining α-bromo group, which was used in a one-pot double Suzuki-Miyaura cross-coupling, enabling facile synthesis of multiply arylated thiophenes. [ABSTRACT FROM AUTHOR]

Synthesis of oligothiophenes of well-defined structures that possess 2-8 thiophene units is performed with a new synthetic strategy involving CH homocoupling of bromothiophenes and cross-coupling with organostannanes. Tolerance of the carbon-bromine bond to the palladium-catalyzed CH homocoupling results in oligothiophenes bearing CBr bonds at the terminal thiophene rings, which allow further transformation by the catalysis of a transition-metal complex. [ABSTRACT FROM AUTHOR]