FULL PAPER DOI: 10.1002/ejoc.201300854 Phosphane-Phosphite Chelators Built on a α-Cyclodextrin Scaffold: Application in Rh-Catalysed Asymmetric Hydrogenation and Hydroformylation Matthieu Jouffroy, [a] David Sémeril, [a] Dominique Armspach,* [a] and Dominique Matt* [a] Keywords: Cyclodextrins / Phosphane ligands / Asymmetric catalysis / Platinum / Rhodium / Cavitands Four hybrid phosphane-phosphite ligands were synthesised by regioselective A,B-functionalisation of a methylated α- cyclodextrin (α-CD) scaffold. In all these ligands the phos- phite part comprises a 2,2'-bisaryloxyphosphanyloxy group. The ligands, which display inherent chirality, readily form 12-membered chelate rings with d 8 -metal ions. In the most flexible chelates (those with an unsubstituted 2,2'-bis- phenoxy group), the metal plane describes a fan-like motion about the P···P' axis with concomitant fast atropisomerisation of the biaryl unit. When the latter is blocked, as in the 2,2'- Introduction Despite the presence of numerous stereogenic centres em- bedded in their rigid skeleton, to date only few cyclodex- trin (CD) derived ligands have been used in asymmetric ca- talysis. In the corresponding metal catalysts the reaction usually takes place outside the cavity, far from the centres of chirality in which efficient asymmetric induction could occur. Nevertheless, when the catalytic centre of these com- plexes is maintained in a rigid manner with respect to the CD backbone, significant ee values can be obtained. Such a feature has been observed, for example, in metallocyclo- dextrins capable of forming transient inclusion complexes in water with prochiral substrates to be transformed. [1] Chiral- ity transfer from the glucose units to the metal first sphere of coordination is also often very effective when rigid che- late complexes are obtained from CDs bearing two close pendant arms. [2] A potential strategy for enhancing chiral induction consists in making the CD shape inherently chiral by anchoring a set of distinct groups on its conical back- bone so as to produce a CD with a substitution pattern non superimposable with its mirror image. [3] However, whether the effects of inherent chirality will synergistically add to those induced by the asymmetric centres of the backbone is difficult to predict. It is worth mentioning here that di- [a] Laboratoire de Chimie Inorganique Moléculaire et Catalyse, Institut de Chimie UMR 7177 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67008 Strasbourg cedex, France E-mail: d.armspach@unistra.fr dmatt@unistra.fr Homepage: http://inorganics.online.fr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201300854. Eur. J. Org. Chem. 2013, 6069–6077 © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 6069 binaphthyloxyphosphites, the fan-like motion no longer takes place. Rhodium complexes of the CDs were assessed in asymmetric hydrogenation of α-dehydroamino acid esters and hydroformylation of styrene. Poor enantiodiscrimination was observed for the highly mobile chelate complexes, whereas the more rigid ones all resulted in significant ee val- ues. The best performing hydrogenation catalyst is the one in which both chiral components – CD and (S)-binaphthyl – behave in a synergistic way. phosphanes based on other inherently chiral macrocycles have already been reported. [3b] In this paper we describe the first inherently chiral CDs bearing two distinct P III substituents, namely a phosphane unit and a phosphite one. These hybrid ligands, which are ideal for chelate formation, have been assessed in the rho- dium-catalysed hydrogenation of α-dehydroamino acid es- ters and hydroformylation of styrene. Chiral phosphanyl- phosphites constitute a class of ligands that have found many applications in asymmetric catalytic transforma- tions, [4] notably hydrogenation [5] and hydroformylation [6] of prochiral olefins. Results and Discussion Synthesis of Phosphane-Phosphite Ligands The synthesis of the ligands started with the deprotection of phosphane borane adduct 1·BH 3 [7] with boiling dieth- ylamine to give 1 quantitatively (Scheme 1). Surprisingly, phosphorochloridites 2–5 did not react with the CD pri- mary hydroxy groups in the presence of a tertiary amine such as Et 3 N, which are the general reaction conditions used for the formation of phosphites from secondary and tertiary alcohols. Only the CD alkoxide obtained by re- acting 1 with NaH in hot toluene, was sufficiently nucleo- philic to give the corresponding phosphane-phosphite li- gands 6–9 with isolated yields ranging from 37 to 62%. The chemical shifts for the two phosphorus donor atoms are typical of phosphite (146.6  δ  150.7 ppm) and di- arylalkylphosphane (–21.4  δ  –20.3 ppm) functionali- ties. All NMR spectra displayed sharp signals at room tem-