Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

Abstract

A new synthetic strategy toward nonracemic phosphoryl-substituted pyrrolidines and tetrahydropyranes with three and five contiguous stereocenters is presented. Readily available β-keto phosphonates react with conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for reactions with aldehydes yielding tetrahydropyranylphosphonates as individual stereoisomers. These nonracemic heterocycles containing phosphoryl moieties are useful for designing new pharmacologically active compounds.

Straightforward Access to High-Performance Organometallic Catalysts by Fluoride Activation: Proof of Principle on Asymmetric Cyanation, Asymmetric Michael Addition, CO2 Addition to Epoxide, and Reductive Alkylation of Amines by Tetrahydrofuran

“…As another example of the versatility of the fluoride activation, we decided to investigate another transformation, namely, asymmetric Michael addition of dimethyl malonate to nitroalkenes. Asymmetric Michael addition reactions have been established as an effective strategy for the formation of C–C and C–heteroatom bonds and have been widely used in natural product synthesis. − In particular, we decided to investigate the effect of fluoride activation on the nickel/diamine-catalyzed enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes, which was reported by the Evans’s group (Figure A) . We were pleased to find that the catalytic performance of the reported system was greatly improved by TBAT addition (Figure B).…”

Fluoride Additive as a Simple Tool to Qualitatively Improve Performance of Nickel-Catalyzed Asymmetric Michael Addition of Malonates to Nitroolefins

“…The role of asymmetric Michael addition is hard to overestimate. − Evans and Seidel developed a highly popular nickel-salan catalyst, allowing us to achieve high yield and enantioselectivity using 2 mol % of the catalyst in general (they discussed that the lowest amount of such a catalyst would be 0.1 mol %). , In our previous work, we showed that the in situ catalyst activation by the fluoride additive allowed us to achieve the same result using as low as 250 ppm of the nickel catalyst (Scheme , b) …”