Synthesis of Chiral, Enantiopure Zirconocene Imido Complexes: Highly Selective Kinetic Resolution and Stereoinversion of Allenes, and Evidence for a Stepwise Cycloaddition/Retrocycloaddition Reaction Mechanism

Abstract

Certain metal ± carbon multiple bonds exhibit substantial reactivity toward organic compounds and are important intermediates in many catalytic processes. [1] The analogous reactivity of metal ± heteroatom multiple bonds, such as those in metal ± imido complexes, has been known for a much shorter time and has only relatively recently been utilized in synthetic applications. [2] We wish to report a series of highly enantioselective reactions using isolable imido complexes with reactive metal ± nitrogen double bonds. [3±9] These involve the reactions of enantiopure (ebthi)(L)Zr NR complexes with 1,3-disubstituted allenes (L tetrahydrofuran; ebthi bis(tetrahydroindenyl)ethane). Our observations a) demonstrate the operation of a general and highly selective kinetic resolution, b) provide the first example of a reaction that can be used to selectively invert the absolute configuration of one (symmetrically or unsymmetrically 1,3-disubstituted) allene enantiomer within a racemic mixture, and c) provide strong mechanistic evidence for the stepwise nature of an organometallic cycloaddition reaction.Previous work in our laboratories has shown that zirconocene ± imido complexes undergo cycloaddition reactions with a wide range of unsaturated organic molecules including alkynes, [10] imines, [11] and certain alkenes. [12] Several of these reactions are important steps in catalytic transformations (for example, hydroamination or imine metathesis) mediated by the imido compounds. To extend this chemistry to systems capable of enantioselective reactions, we decided to examine the reactions of chiral disubstituted allenes with zirconium imido complexes bearing the C 2 -symmetric ebthi ligand developed by Brintzinger. [13] The chiral imido complexes were synthesized in two steps from the known dimethyl complex 4, as shown in [Eq. (1)]. [14] In order to investigate the products and diastereoselectivity of the chiral zirconocene ± allene reactions, we first examined the stoichiometric reactions of racemic ebthi complexes 1 and 2 with achiral allenes and racemic chiral 1,3-disubstituted allenes. The purple metallacycle rac-6 was formed rapidly upon condensation of allene onto a benzene solution of rac-1 [Eq. (2)]. Production of an azametallacycle with the exocyclic methylene group in the b (as opposed to the a) position was indicated by its 1 H, 1 H NOESY spectrum, which featured a strong NOE between one of the exocyclic methylene protons and the methyl groups on the phenyl ring. H 2 C C CH 2 Zr N Ar NAr THF + (2) rac-6 Zr rac-1 β α (rac)-(rac)-The reaction of rac-1 with 1 equiv of racemic 1,3-diphenylallene, 3,4-heptadiene, 4,5-nonadiene, or 1,2-cyclononadiene at 23 8C provided a single diastereomeric product in each case, as determined by 1 H and 13 C NMR spectra ([Eq. (3)]). A bulky imido substituent is required for the selectivity in these transformations, as an 85:15 mixture of diastereomers was formed from the reaction of the p-tolylimido complex rac-2 with diphenylallene. These results were encouraging because they sugge...

Kinetics and Mechanism of the Racemization of Aryl Allenes Catalyzed by Cationic Gold(I) Phosphine Complexes

“…In addition to these catalytic processes, planar η 1 ‐allylic cation intermediates have been invoked to account for the stereomutation of chiral iron,33 platinum,34 and silver35 allene complexes. Bergman reported the stoichiometric stereoinversion and racemization of 1,3‐disubstituted allenes by a zirconocene imido complex that was proposed to occur through stereospecific [2+2] cycloaddition followed by racemization of the resulting azazirconacyclobutane 36…”

Effizienz in der nichtenzymatischen kinetischen Racematspaltung

“…In einem anderen Fall wurde die Enantiokonvergenz auf der Stufe des reaktiven Intermediats erreicht. Andersen, Bergman et al berichteten über die kinetische Racematspaltung chiraler Allene mithilfe des chiralen Zirconiumimido‐Komplexes 82 (Schema ) 44. Hierbei lieferten sowohl das schnell als auch das langsam reagierende Enantiomer des 1,2‐Cyclononadiens 83 letztlich das gleiche Hauptprodukt 85 .…”

“… Enantiokonvergenz auf der Stufe des reaktiven Intermediats bei der kinetischen Racematspaltung chiraler Allene 44…”

Enantioselektive Synthese von und mit Allenen

“…Konzeptionell gänzlich andere Wege zu enantiomerenangereicherten und ‐reinen Allenen basieren auf gerüstaufbauenden Synthesemethoden (z. B. enantioselektiven Wittig‐Horner‐Wadsworth‐Emmons(WHWE)‐Reaktionen von Ketenen11) sowie auf kinetischen Racematspaltungen 12, 13. So zeigten Hoppe et al,13 dass die Deprotonierung des prochiralen sekundären Alkinylcarbamats 16 mit n ‐Butyllithium in Gegenwart von (−)‐Spartein 17 in Pentan zur spontanen Kristallisation des diastereomerenreinen Komplexes 18 führt (Schema ).…”