Enantioselective Synthesis of DIANANE, a Novel C₂-Symmetric Chiral Diamine for Asymmetric Catalysis

Abstract

DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C(2)-symmetric diamine, based on the rigid bicyclo[2.2.1]heptane scaffold. Schiff-base ligands derived from DIANANE have already found use in asymmetric catalysis, e.g., in the highly enantioselective Nozaki-Hiyama-Kishi reaction. We herein describe a practical synthesis of enantiomerically pure DIANANE, starting from norbornadiene in four steps: (i) Pd-MOP catalyzed Hayashi-hydrosilylation/Tamao-Fleming oxidation, (ii) oxidation to norbornane-2,5-dione, (iii) endo-selective reductive amination with benzylamine, and (iv) hydrogenolytic debenzylation. None of the steps involves chromatographic purification. For the Tamao-Fleming oxidation, the use of hydrogen peroxide in the form of its urea clathrate instead of aqueous solution proved beneficial. By the above sequence, enantiomerically pure (ee >or=99%) DIANANE was obtained from norbornadiene in 40-50% overall yield. The relative and absolute configuration of DIANANE was confirmed by X-ray crystallography of the DIANANE bis-tosylamide, and of its bis-camphorsulfonamide. Furthermore, the synthesis and X-ray crystal structure of the Schiff-base ligand derived from DIANANE and 3,5-di-tert-butyl salicylic aldehyde are reported.

Cr/Ni‐Catalyzed Vinylation of Aldehydes: A Mechanistic Study on the Catalytic Roles of Nickel and Chromium

“… Proposed mechanistic scheme for the Cr/Ni‐catalyzed vinylation of aldehydes: The chromium(III) alkoxide formed was trapped by means of TMSCl6 or [Cp 2 ZrCl 2 ],10b liberating the chromium(III) species, which is converted to the active chromium(II) species by manganese powder as the stoichiometric reductant, thus propagating the catalytic cycle. …”

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…In parallel with the work of Kishi and co-workers, Berkessel et al used the chromium (II) complex preformed in situ from chiral salen-type ligand 144 (Figure 4). [178] However, the enantiomeric excess obtained was relatively moderate (Scheme 78). This catalytic system was then used in the synthesis of desmethyl analogues of laulimalide, which exhibits nanomolar activity against cancer cell lines and is, therefore, an interesting structure for the development of anticancer agents (Scheme 79).…”

Schmidt Rearrangement Reactions with Alkyl Azides

“…72,73 The total synthesis began with the interesting, useful, and C 2 -symmetric ketone 67 , which was readily derived from norbornadiene using a doubly asymmetric hydrosilylation reaction originally reported by Hayashi (Scheme 7.41 ). 74,75 The most direct route from this compound to sparteine would involve two Schmidt reactions, possibly simultaneous, that would provide a bislactam precursor. Although, a single intramolecular Schmidt reaction could be carried out, it was not possible to carry out a second Schmidt reaction on alkylated lactams related to 68 .…”