The reaction of allyl bromide with phenylacetylene catalyzed by Pd/Al2O3 pellets and Pd/C powder was investigated. Bromoallylation of phenylacetylene took place to give a regioisomeric mixture of 1-bromo-substituted 1,4-dienes. The bromoallylation of phenylacetylene was successfully applied to a continuous flow synthesis using a stainless steel made column packed with Pd/Al2O3 pellets.
Lactonization of dialdehydes and keto aldehydes was effectively catalyzed by RuHCl(CO)(PPh3)3. A cascade lactonization sequence accompanied by cross-coupling with enones was also attained.
Sonogashira coupling reaction leading to a matrix metalloproteinase inhibitor was investigated using an automated microreactor system, which is a sequential temperature- and flow rate-programed reaction evaluation system. By repeating the use of this computer-controlled system four times, we were able to determine the optimal conditions and quickly apply them to a 10 g scale synthesis using the same microreactor system. The optimal conditions were also applied to a 100 g scale production by using another microflow system composed of a T-shaped micromixer (200 μm id) and a stainless tube reactor (2000 μm id and 20 m length). Total time spent for both optimization and production was as short as 50 h.
Organocatalytic enantioselective cycloadditions providing nitrogen-substituted dihydropyran-2-ones were developed in two catalytic systems. The (3R,4R)-product was a versatile intermediate in the synthesis of 1β-methylcarbapenem antibiotics.
Highly efficient thermal radical carboaminoxylations of various olefins by using the novel alkoxyamine A to give adducts of type B are described. It is reported that these radical addition reactions can be performed in a microflow reaction system. As compared to conventional batch reaction setup, significantly higher yields are obtained by running carboaminoxylations using the microflow system under analogous conditions.
The Barton reaction (nitrite photolysis) of a steroidal substrate 1, to give 2, a key intermediate for the synthesis of myriceric acid A, an endothelin receptor antagonist, was successfully carried out in a continuous microflow system using a Pyrex glass-covered stainless-steel microreactor having a one lane microchannel (Type A: 1000 μm width, 107 μm depth, 2.2 m length). We found that using a low-power black light (peak wavelength: 352 nm) and UV-LED light (peak wavelength: 365 nm) as the light source will suffice for the Barton reaction, creating a compact energy-saving photo-microreaction system. A multi-gram-scale production was attained using a multi-lane microreactor (Type B: 1000 μm width, 500 μm depth, 0.5 m length, 16 lanes) in conjunction with a black light.