Synthesis of Chiral 2‐Phospha[3]ferrocenophanes and their Behaviour as Organocatalysts in [3+2] Cyclization Reactions

Abstract

Planar chiral 2-phospha[3]ferrocenophanes have been prepared via a stereoselective three-step synthesis. The key step is the lithiation of the 1,1'-di-A C H T U N G T R E N N U N G substituted ferrocene 11 bearing (S)-2-(methoxymethyl)pyrrolidines as the chiral ortho-directing groups. The diastereoselectivity of these reactions has been mastered by an appropriate choice of the metallating agent, so as to afford a suitable access to C 2 -symmetrical, tetrasubstituted ferrocenes. These compounds have been converted into the enantiomerically pure 2-phospha[3]-ferrocenophanes 16, via the corresponding acetates and their reactions with primary phosphines. Phosphines 16 have been used as nucleophilic catalysts in model cyclization reactions. Unlike 2-phospha[3]-ferrocenophanes with stereogenic acarbons, the planar chiral derivatives 16 proved to be suitable catalysts for these processes. Thus, for instance, phosphine 16c successfully promotes the enantioselective [3 + 2] annulations of allenes and enones into functionalized cyclopentenes (ees up to 96%). Among others, spirocyclic derivatives have been obtained in good yields and ees in the range 77-85%. The robustness of this catalyst has been demonstrated by recycling experiments.

Phosphine Organocatalysis

“…With these sterically demanding alkenes, excellent regioselectivities and enantioselectivities were accomplished when using Gladiali’s phosphepine ( S )- P48 as the catalyst, providing a functionalized cyclopentene and a spirooxindole. 299–301…”

Phosphine Organocatalysis for the Synthesis of Spirocyclic Compounds

“…20,21 The corresponding spirocyclic indanones were obtained, via γ-addition, in moderate to high yields and up to 85% ee (Scheme 14). In some cases (entries 4, 6 and 7), we observed, by 1 H NMR spectroscopy, traces of the putative α-adduct in the crude mixtures.…”

Enantioselective Construction of All‐Carbon Quaternary Stereogenic Centers by Using Phosphine Catalysis

“…In 2008, Marinetti and co‐workers reported a new class of chiral phosphines based on a planar chiral 2‐phospha[3]ferrocenophane scaffold ( P11 ) that effectively catalyzed the Lu [3+2] annulation of allenic esters 10 with indanone‐derived exocyclic enones 11 to yield spirocyclic structures that contained a quaternary center with moderate enantioselectivities (Scheme a) . With dienones 13 , the annulation reaction tolerated substrates that contained aryl groups of different electronic natures, and high enantioselectivities were obtained (Scheme b) .…”