Stereodivergent Synthesis of Camphor-Derived Diamines and Their Application as Thiourea Organocatalysts

Abstract

<jats:p>A series of 18 regio- and stereo-chemically diverse chiral non-racemic 1,2-, 1,3-, and 1,4-diamines have been synthesized from commercial (1S)-(+)-ketopinic acid and (1S)-(+)-10-camphorsulfonic acid. The structures of the diamines are all based on the d-(+)-camphor scaffold and feature isomeric diversity in terms of regioisomeric attachment of the primary and the tertiary amine function and the exo/endo-isomerism. Diamines were transformed into the corresponding noncovalent bifunctional thiourea organocatalysts, which have been evaluated for catalytic activity in the conjugative addition of 1,3-dicarbonyl nucleophiles (dimethyl malonate, acetylacetone, and dibenzoylmethane) to trans-β-nitrostyrene. The highest enantioselectivity was achieved in the reaction with acetylacetone as nucleophile using endo-1,3-diamine derived catalyst 52 (91.5:8.5 er). All new organocatalysts 48–63 have been fully characterized. The structures and the absolute configurations of eight intermediates and thiourea derivative 52 were also determined by X-ray diffraction.</jats:p>

Synthesis and Catalytic Activity of Bifunctional Phase-Transfer Organocatalysts Based on Camphor

“…Camphor-derived endo -diamines 1a , b and exo -diamines 2a were prepared in four steps from commercially available (1 S )-(+)-10-camphorsulfonic acid ( Scheme 1 ) [ 29 , 30 ]. Camphorsulfonic acid was transformed into 10-iodocamphor in an Apple-type reaction, followed by nucleophilic substitution with pyrrolidine or dimethylamine in dimethyl sulfoxide.…”

“…As part of our ongoing study of camphor-based diamines as potential organocatalyst scaffolds [ 29 ], we reported the synthesis of 1,3-diamine-based bifunctional squaramide organocatalysts prepared from camphor and their application as efficient catalysts in Michael additions of 1,3-dicarbonyl compounds and pyrrolones as nucleophiles to trans -β-nitrostyrene derivatives [ 30 , 31 ]. Extending this work, we report here the synthesis of a new type of 1,3-diamine-based bifunctional quaternary ammonium salt phase-transfer organocatalyst ( Figure 1 ) and its evaluation in the electrophilic α-functionalization of β-keto ester and the alkylation of a glycine-derived Schiff base with methyl acrylate.…”

Double Spirocyclization of Arylidene-Δ2-Pyrrolin-4-Ones with 3-Isothiocyanato Oxindoles

“…Organocatalysts Ia [70], II [69], IIIa [70], IV [70], Vb [74], VIa [75], VIb [76], VIIa [77], VIIb [76], IXa [78], IXb [79], IXc [80], Xb [81], XIa [19], and XIb [78] were prepared following the literature procedures; organocatalysts VIIIb and XII were purchased from Sigma-Aldrich. To a solution of methyl (Z)-2-(2-chloroacetyl)-3-(methylamino)but-2-enoate (E) [71] (1 equivalent) in anhydrous EtOH at room temperature, KOH (1.05 equivalent, ω = 0.85) was added and the resulting reaction mixture was heated to 75 • C. After the disappearance of the starting material (ca.…”

New bifunctional 1,3‐diamine organocatalysts derived from (+)‐camphoric acid for asymmetric Michael addition of 1,3‐dicarbonyl compounds to nitroolefins

“…(+)‐Camphoric acid was chosen as the precursor because it is an inexpensive source of chirality, readily available in both enantiomeric forms and has been used as a ligand on enantioselective metallic catalysis with good results 44 . Moreover, most of the organocatalysts synthesized in this report have the advantage of being easily prepared in a synthetic sequence of only two steps from (+)‐camphoric acid, differently from the 1,3‐diamine bifunctional organocatalysts reported in the literature 36–43 …”

“…Bifunctional 1,3‐diamine thiourea and squaramide organocatalysts derived from camphor were also used for the same transformations; however, these organocatalysts required five to nine synthetic steps (Figure 1). 40,41 Likewise, 1,3‐diamine‐tethered guanidium/bisthiourea organocatalysts have been used in Michael reactions between 1,3‐dicarbonyl compounds and nitroolefins 42 and in the enantioselective phospha‐Michael reaction of diphenyl phosphonate to nitroolefins (Figure 1). 43 …”