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Abstract:
The development of novel highly acidic Brønsted and Lewis acid organocatalysts is described in this thesis. These rationally designed and synthesized N−H acidic phosphoramidimidates, iminoimidodiphosphates (iIDP), and imidodiphosphorimidates (IDPi) enabled catalytic asymmetric transformations inaccessible by previous organocatalysts. While a systematic modification of the proton donor in BINOL derived phosphoric acids was the focus of previous investigations, this work focused instead on the systematic sub- stitution of the proton acceptor ((RO)2P(B)AH, B: Lewis donor, AH: Brønsted donor). The reduction of the Lewis basicity (=B) significantly increased the catalytic performance in synthesized phosphoramidimi- dates, iIDPs, and IDPis. These catalyst scaffolds vanished former limitations in asymmetric α-tocopherol, functionalized tetrahydropyran, and homoallylic alcohol syntheses. In particular, phosphoramidimidates were demonstrated to enable the direct asymmetric α-tocopherol synthesis from trimethylhydroquinone and isophytol in a single flask transformation, while previously reported BINOL-derived phosphates were insufficiently active for this transformation. Iminoimidodiphosphate Brønsted acid catalysts allowed the first general asymmetric Prins cyclization of both aliphatic and aromatic aldehydes furnishing diverse 4-methylenetetrahydropyrans in good to excellent yields and enantiomeric ratios. In this context, iIDP catalysts provided an efficient and scalable enantioselective approach to various fragrances, such as rose oxide and doremox. Most significantly, imidodiphosphorimidate confined pre-Lewis acids catalyzed the asymmetric addition of allyltrimethylsilane to aliphatic and aromatic aldehydes furnishing homoallylic al- cohols in good to excellent yields and enantioselectivities. This Hosomi−Sakurai reaction was realized with IDPi loadings ranging from 0.05 to 2.0 mol%. These extremely active acid catalysts feature a highly tun- able and sterically demanding active site and selectively process small and loosely bound substrates. The C2-symmetric IDPi anion with a single catalytically relevant and geometrically constrained bifunctional active site are expected to find wide utility in various asymmetric reactions.
