Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

A total synthesis of lamellarins U and A3 is described. The synthesis features interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation using (TMP)MgCl·LiCl (TMP: 2,2,6,6-tetramethylpiperidide) as 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.

Mechanism of Base-Catalyzed Halogen Dance Reactions and the Role of Bromo-Bridged Transition States

Base-catalyzed halogen dance reaction, has puzzled chemists ever since, to come up with new ideas regarding the mechanism of this beautiful chemical transformation. Series of fast metal-halogen exchanges are among the most recent mechanisms. Using DFT-Cam-B3LYP/ land2dz computations and focused on Halogen Dance (HD) reactions of bromobenzene derivatives, new bromo-bridged Transition States (TS) are proposed. These are then used to lay out 8 possible isomerization and 18 possible disproportionation paths. Mechanistic pathways were then analyzed based on TS’s energy and protonation/deprotonation steps to find the most suitable pathways. Overall pattern of these mechanisms draws for the first-time a cascade-like pattern for base-catalyzed halogen dance in its entirety. The present work shed light on a dynamic domino mechanism which dominates the realm of nonaqueous strongly basic medium reactions. Trends like these may well be a shared feature in base digestion of wood for its precious poly aromatic component like lignin.

Ester dance reaction on the aromatic ring

Aromatic rearrangement reactions are useful tools in the organic chemist’s toolbox when generating uncommon substitution patterns. However, it is difficult to precisely translocate a functional group in (hetero) arene systems, with the exception of halogen atoms in a halogen dance reaction. Here, we describe an unprecedented “ester dance” reaction: a predictable translocation of an ester group from one carbon atom to another on an aromatic ring. Specifically, a phenyl carboxylate substituent can be shifted from one carbon to an adjacent carbon on a (hetero) aromatic ring under palladium catalysis to often give a thermodynamically favored, regioisomeric product with modest to good conversions. The obtained ester moiety can be further converted to various aromatic derivatives through the use of classic and state-of-the-art transformations including amidation, acylations, and decarbonylative couplings.

Ester Dance Reaction on the Aromatic Ring

Aromatic rearrangement reactions are useful tools in the organic chemist’s toolbox when generating uncommon substitution patterns. However, it is difficult to precisely translocate a functional group in (hetero)arene systems, with the exception of halogen atoms in a halogen dance reaction. Herein, we describe an unprecedented “ester dance” reaction: a predictable translocation of an ester group from one carbon atom to another on an aromatic ring. Specifically, a phenyl carboxylate substituent can be shifted from one carbon to an adjacent carbon on a (hetero)aromatic ring under palladium catalysis to often give a thermodynamically favored, regioisomeric product with modest to good conversions. The obtained ester moiety can be further converted to various aromatic derivatives through the use of classic as well as state-of-the-art transformations including an amidation, acylations and decarbonylative couplings.

Ester Dance Reaction on the Aromatic Ring

Aromatic rearrangement reactions are useful tools in the organic chemist’s toolbox when generating uncommon substitution patterns. However, it is difficult to precisely translocate a functional group in (hetero)arene systems, with the exception of halogen atoms in a halogen dance reaction. Herein, we describe an unprecedented “ester dance” reaction: a predictable translocation of an ester group from one carbon atom to another on an aromatic ring. Specifically, a phenyl carboxylate substituent can be shifted from one carbon to an adjacent carbon on a (hetero)aromatic ring under palladium catalysis to often give a thermodynamically favored, regioisomeric product with modest to good conversions. The obtained ester moiety can be further converted to various aromatic derivatives through the use of classic as well as state-of-the-art transformations including an amidation, acylations and decarbonylative couplings.

Asymmetric synthesis of hetero-1,2,3,4,5-pentasubstituted ferrocenes

A four-step approach toward the first hetero-1,2,3,4,5-pentasubstituted ferrocene derivatives was successfully explored. Starting from Ugi's amine, enantioenriched compounds were made through the first asymmetric halogen ‘dance’ reaction reported.