Flash generation of a highly reactive Pd catalyst for Suzuki-Miyaura coupling by using a flow microreactor.

Superflash! Flash chemistry enables the use of highly reactive unstable species as catalysts for chemical synthesis. Fast micromixing of a solution of [Pd(OAc)(2)] and that of tBu(3) P in 1:1 mole ratio gave a solution of a highly reactive unstable species, which was immediately transferred to a vessel by using a flow microreactor, in which Suzuki-Miyaura coupling was conducted (see scheme).

Cross-coupling of aryllithiums with aryl and vinyl halides in flow microreactors.

The use of Pd catalysts that contained a carbene ligand, such as PEPPSI-SIPr, speeded up the Murahashi coupling of ArLi with ArBr, by enabling its integration with the Br/Li exchange of ArBr with BuLi in flow. Space integration realized the rapid cross-coupling of two different ArBr substrates. However, the cross-coupling reaction with vinyl halides could not be achieved under similar conditions. Pd(OAc)(2) was an effective catalyst, and the space integration of the Br/Li exchange of ArBr with BuLi and the Murahashi coupling with vinyl halides was successfully achieved.

Hysteretic Tricolor Electrochromic Systems Based on the Dynamic Redox Properties of Unsymmetrically Substituted Dihydrophenanthrenes and Biphenyl-2,2'-Diyl Dications: Efficient Precursor Synthesis by a Flow Microreactor Method.

A series of biphenyl-2,2'-diylbis(diarylmethanol)s 3, which have two kinds of aryl groups at the bay region, were efficiently obtained by integrated flow microreactor synthesis. The diols 3NO/NX are the precursors of unsymmetric biphenylic dications 2NO/NX2+, which are transformed into the corresponding dihydrophenanthrenes 1NO/NX via 2NO/NX+• upon reduction, when they exhibit two-stage color changes. On the other hand, the steady-state concentration of the intermediate 2NO/NX+• is negligible during the oxidation of 1NO/NX to 2NO/NX2+, which reflects unique tricolor electrochromicity with a hysteretic pattern of color change [color 1→color 2→color 3→color 1].

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems.

A microflow system consisting of micromixers and microtube reactors provides an effective method for the introduction of two electrophiles onto dibromobiaryls. Selective monolithiation of dibromobiaryls, such as 2,2'-dibromobiphenyl, 4,4'-dibromobiphenyl, 2,7-dibromo-9,9-dioctylfluorene, 2,2'-dibromo-1,1'-binaphthyl, and 2,2'-dibromobibenzyl with 1 equiv of n-butyllithium followed by the reaction with electrophiles was achieved using a microflow system by virtue of fast micromixing and precise temperature control. Sequential introduction of two different electrophiles was achieved using an integrated microflow system composed of four micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds.

Selective monolithiation of dibromobiaryls using microflow systems.

Selective monolithiation of dibromobiaryls, such as 2,2'-dibromobiphenyl, 4,4'-dibromobiphenyl, 2,7-dibromo-9,9-dioctylfluorene, 2,2'-dibromo-1,1'-binaphthyl, and 5,5'-dibromo-2,2'-bithiophene, with 1 equiv of n-butyllithium followed by the reaction with electrophiles was achieved using a microflow system by virtue of fast micromixing and precise temperature control. Sequential introduction of two different electrophiles based on this method was also achieved using a microflow system composed of four micromixers and four microtube reactors.

Integrated micro flow synthesis based on sequential Br-Li exchange reactions of p-, m-, and o-dibromobenzenes.

A micro flow system consisting of micromixers and microtube reactors provides an effective method for the introduction of two electrophiles onto p-, m-, and o-dibromobenzenes. The Br-Li exchange reaction of p-dibromobenzene with nBuLi can be conducted by using the micro flow system at 20 degrees C, although much lower temperatures (< -48 degrees C) are needed for a batch reaction. The resulting p-bromophenyllithium was allowed to react with an electrophile in the micro flow system at 20 degrees C. The p-substituted bromobenzene thus obtained was subjected to a second Br-Li exchange reaction followed by reaction with a second electrophile at 20 degrees C in one flow. A similar transformation can be carried out with m-dibromobenzene by using the micro flow system. However, the Br-Li exchange reaction of o-dibromobenzene followed by reaction with an electrophile should be conducted at -78 degrees C to avoid benzyne formation. The second Br-Li exchange reaction followed by reaction with an electrophile can be carried out at 0 degrees C. By using the present method, a variety of p-, m-, and o-disubstituted benzenes were synthesized in one flow at much higher temperatures than are required for conventional batch reactions.