Preparation and Characterization of NewC₂‐ andC₁‐Symmetric Nitrogen, Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL. Part III

Abstract

A brief overview is presented of the field of organocatalysis using chiral H‐bond donors, chiral Brønsted acids, and chiral counter‐anions (Fig. 1). The role of TADDOLs (=α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols) as H‐bond donors and the importance of an intramolecular H‐bond for acidity enhancement are discussed. Crystal structures of TADDOLs and of their N‐, S‐, and P‐analogs (Figs. 2 and 3) point the way to proposals of mechanistic models for the action of TADDOLs as organocatalysts (Scheme 1). Simple experimental two‐step procedures for the preparation of the hitherto strongest known TADDOL‐derived acids, the bicyclic phosphoric acids (2 in Scheme 2) and of a phosphoric‐trifluorosulfonic imide (9 in Scheme 4), are disclosed. The mechanism of sulfinamide formation in reactions of TADDAMIN with trifluoro‐sulfonylating reagents is discussed (Scheme 3). pKa Measurements of TADDOLs and analogs in DMSO (reported in the literature; Fig. 5) and in MeO(CH2)2OH/H2O (described herein; Fig. 6) provide information about further possible applications of this type of compounds as strong chiral Brønsted acids in organocatalysis.

Green Chemistry Meets Asymmetric Organocatalysis: A Critical Overview on Catalysts Synthesis

“…[161] The great majority of phosphoramides has been obtained from a BINOL or a [H 8 ]‐BINOL scaffold (BNPAs). [162] A scarce number of phosphoramides has been synthesized from TPAs [157b] or VPAs,[ 128 , 163 ] without finding any successful application in asymmetric organocatalysis. On the contrary, STRIP‐ N ‐triflyl phosphoramide is the privileged organocatalyst for rearrangement of epoxides to aldehydes, [3+2]‐cycloaddition between hydrazones and alkenes, the one‐pot synthesis of tetrahydroquinolines with the simultaneous control on the formation of up to three stereocentres and the desymmetrization of oxetanes to tetrahydrothiophenes and tetrahydroselenophenes.…”

2-(Dibenzylamino)butane-1,4-dithiol (DABDT), a Friendly Disulfide-Reducing Reagent Compatible with a Broad Range of Solvents

“…First, we attempted the formation of iso-thiouronium salts using thiourea, which affords sodium salt of thiolate upon reaction with NaOH. However, the dithiane along with the thiolane was obtained mainly as products . Second, we attempted thioester formation using potassium thioacetate.…”

“…However, the dithiane along with the thiolane was obtained mainly as products. 21 Second, we attempted thioester formation using potassium thioacetate. In this case, S,S′-[2-(dibenzylamino)butane-1,4-diyl] diethanethioate (4) was obtained in high yield and purity (see the Supporting Information and Figures S15−S21).…”

Investigations Concerning the Syntheses of TADDOL-Derived Secondary Amines and Their Use To Access Novel Chiral Organocatalysts

“…Although TADDOLs are omnipresent as ligands in (transition) metal catalysis 2 and tartaric acid is a versatile starting material for preparing important chiral compounds, 3 the use of these easily available natural chiral pool-based starting materials to obtain asymmetric organocatalysts has so far been limited to a few (but often impressive) examples only. 4-6 Whilst our initial investigations on the syntheses of TADDOL-derived sulfonimides failed, 7 we recently created a small library of novel TADDOL-derived N-spiro quaternary ammonium salts 3 , which were found to be powerful phase-transfer catalysts (PTCs) for the stereoselective α-alkylation of glycine Schiff bases. 8 Encouraged by these promising initial results we have now undertaken systematic investigations concerning the syntheses and applicability of TADDOL-derived secondary amines 4 2,9 and 5 to synthesize a variety of structurally diverse novel chiral Lewis base catalysts 10 6 – 9 and chiral phase-transfer catalysts 11 3 , 10 – 12 (Scheme 1).…”