WO2012122407A2

WO2012122407A2 - Chiral calixarenes

Info

Publication number: WO2012122407A2
Application number: PCT/US2012/028350
Authority: WO
Inventors: Partha Nandi; Alexander Katz
Original assignee: The Regents Of The University Of California
Priority date: 2011-03-08
Filing date: 2012-03-08
Publication date: 2012-09-13
Also published as: WO2012122407A3

Abstract

In various embodiments, this invention provides a modular approach to build chiral calixarene phosphite and phosphate ligands that appends the chirality of readily available chiral diols (e.g., BINOL, VANOL, VAPOL etc) via corresponding chlorophosphite or chlorophosphate. This library of chiral ligands can be valuable for a number of asymmetric catalysis (e.g., asymmetric reduction, hydroformylation, sulfoxidation, epoxidations and chiral Bronsted acid catalysis). With calix[4]arene BINOL phosphite more than 99% enantiomeric excess in a catalytic MPV reduction of ketone was obtained.

Description

CHIRAL CALIXARENES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims under 35 USC 1 19(e) the benefit of US Provisional Application No. 61/450,577, filed March 8, 201 1 , which is incorporated herein by reference in its entirety for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0002] This work was supported by a grant from the United States Department of Energy (DOE) (DE-FG02-05ER15696). The Government has certain rights in the subject matter disclosed herein.

FIELD OF THE INVENTION

[0003] This invention relates to calixarenes and related compounds. More specifically, the invention relates to chiral calixarenes and related compounds coordinated to a metal. More particularly, this invention provides chiral calixarene phosphites and chiral calixarene phosphates. These chiral species can be coordinated to a metal. The coordinated compounds can be immobilized on the surface of a substrate.

BACKGROUND OF THE INVENTION

[0004] Calixarenes are a well-known class of cyclic oligomers that are usually made by condensing formaldehyde with p-alkylphenols under alkaline conditions. V. Bohmer summarized the chemistry of calixarenes in an excellent review article (Angew. Chem., Int. Ed. Engl. 34: 713 (1995). Early transition metal complexes in which the four oxygen atoms of calix[4]arenes or O-methylated calix[4]arenes chelate to the metal are now known (see, e.g., J. Am. Chem. Soc. 1 19: 9198 (1997)). [0005] Metal cluster compounds constitute a group of compounds which have favorable properties as catalysts and catalyst precursors. In U.S. Pat. No. 4,144,191, a bimetallic carbonyl cluster compound catalyst for producing alcohols by

hydroformylation is disclosed; either Rli2Co2(CO)i2 or RhsCo(CO)i2 is used, bound to an organic polymer containing amine groups. The catalyst operates at low temperature and produces almost exclusively alcohols.

[0006] In the Finnish patent application No. 844634 the observation is made that a mixture of the monometal cluster compounds Rh (CO)i2 and Co (CO)i2 bound to an amine resin carrier serves as the extremely selective catalyst in producing alcohols. An advantage of the cluster mixture catalyst is that it is simpler to prepare and its activity can be optimized as a function of the mole proportion of the metals.

[0007] It is known that the chemical properties of metal clusters such as catalytic activity or physical properties such as magnetism vary depending on the size of cluster (aggregate of atoms) and the nature and number of ligands.

[0008] Some catalytic effects of transition metals complexed with calixarenes have been shown for olefin rearrangements [Giannini et al., J. Am. Chem. Soc. 121 : 2797

(1999) ], cycloadddition of terminal alkanes [Ozerov et al., J. Am. Chem. Soc. 122: 6423

(2000) ] and hydroformylation [Csok et al., J. OrganometaUic Chem. 570: 23 (1998)]. The calixarenes in those investigations were coordinated with a metal cluster or a metal nanoparticle.

[0009] Coordinating a calixarene ligand to metal clusters offers numerous advantages including, but not limited to, more resiliency against aggregation due to the role of the calixarene as a sterically bulky barrier and, perhaps more importantly, opens the synthesis of new classes of highly tailorable functional materials, in which the calixarene serves as a nanoscale organizational scaffold for the assembly of complex active sites.

[0010] Quite surprisingly, the inventors have discovered a straightforward method of preparing chiral calixarene ligands, such as those based on phosphates and phosphites. These new ligands provide an entry point into the rich chiral catalyst chemistry of metal coordinated calixarene-related compounds. SUMMARY OF THE INVENTION

[0011] The present invention provides novel chiral calixarene -related molecules and organometallic compounds comprised of calixarene-related moieties complexed with a metal. Moreover, there is provided a generalized approach for the synthesis of chiral calixarene-related moieties. In exemplary embodiments, the invention also provides a method of controlling aspects of the reactivity of metals by coordination with chiral calixarene-related moieties.

[0012] In an exemplary embodiment, the invention provides a chiral calixarene-related compound comprising one or more chiral phophite or phosphate moieties bound to the lower rim of the calixarene-related compound through a -0-P(0)2R^p linkage in which R^p is the organic component of the ligand. Prior to the present invention, there were no examples of chiral calixarene phosphite and phosphate ligands formed through a

-0-P(0)2P^P linkage between a bidentate phosphine ligand and an oxygen of the lower rim of the calixarene.

[0013] Thus, in an exemplary aspect, the invention provides a chiral calixarene-related compound comprising, (a) a chiral organic ligand comprising phosphorus; (b) a calixarene-related moiety wherein said chiral organic species is bound to the lower rim of the calixarene-related compound through a -0-P(0)2R^p or -0-P(0)(0)2R^p (phosphate) linkage between a phosphine ligand derived from a chiral diol and an oxygen of the lower rim of the calixarene. R^p is the diol-derived chiral organic component of the ligand and in exemplary embodiments is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl moieties. In exemplary embodiments, the calixarene-related compounds of the invention include the phosphorus atom bound to 1 , 2 or 3 of the oxygen atoms of the lower rim of the calixarene-related compound. In various embodiments, at least one of the oxygens of the lower rim is present as OH.

[0014] In a further exemplary aspect, the invention provides an organometallic compound comprising a metal atom complexed to a chiral calixarene-related phosphite or phosphate compound described above. In an exemplary embodiment, the metal atom is coordinated through a single oxygen atom of the lower rim of the calixarene-related compound, and in another exemplary embodiment, the metal atom is coordinated to two oxygen atoms of this compound.

[0015] The present invention can be practiced with any metal atom that can coordinate with a coordinating atom on a linker component of a calixarene-related molecule.

Exemplary metals include Al, Vn, Ti, Sc, Ze, Nb, Sn, Y, Ru, Ta, lanthanides (e.g., La, Sm), and actinides. In various exemplary embodiments, the metal atom is Al.

[0016] This invention also relates to the immobilization of a metal atom coordinated to a chiral calixarene-related phosphite or phosphate compound described above on a substrate. In an exemplary embodiment, the metal atom is bound to the substrate. The metal atom can be bound first to a substrate and subsequently complexed to a calixarene or the metal atom complexed to the calixarene-related compound can be bound to the substrate. Alternatively, the metal cluster/nanoparticle can be contacted with a substrate to which a calixarene-related moiety is bound, thereby forming the immobilized complex. Methods of tethering calixarenes to surfaces are generally known in the art. See, for example, U.S. Pat. Appl. Pub. No. 2005/0255332.

[0017] Exemplary substrate components include, but are not limited to metals, inorganic oxides, glasses and polymers. A non-limiting list of useful substrates includes, silicon, tungsten, niobium, titanium, zirconium, manganese, vanadium, chromium, tantalum, aluminum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron. Metal oxides and zeolites (intact and delaminated) are exemplary substrates of use in conjunction with the compounds of the invention.

[0018] In an exemplary embodiment, the substrate is an inorganic oxide. In this embodiment, an exemplary immobilization process includes contacting the metal coordinated to the calixarene-related compound with a substrate. The substrate is optionally surface-modified by reaction with one or more polyhalides and/or

polyalkoxides of an element capable of forming a stable aryloxide species with the substrate, or reacting the substrate with a calixarene or calixarene-related compound that has been previously modified or derivatized by reaction with said one or more polyhalides and/or polyalkoxides. In various embodiments, the immobilization process includes reacting a halide, alkoxide or reactive alkyl derivate of the complexed metal atom with a substrate with which the metal derivative is reactive. An exemplary substrate is a silicon oxide.

[0019] The invention also includes methods of utilizing the calixarene-related moiety complexed metal cluster/nanoparticle compositions of the invention in various chemical processes. An exemplary process is catalysis. The compositions of the invention are useful as catalysts in a number of processes including, without limitation, hydrogenation, hydride shift (e.g., Meerwein-Ponndorf-Verley), carbonylation of organic substrates, e.g., carbonylation of methane to form acetic acid, epoxidation, etc.

[0020] Other exemplary aspects, objects and advantages of the invention are set forth in the detailed description that follows and the claims appended hereto.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 is a design of a calix[4]arene framework for MPV reduction.

[0022] FIG. 2 is a design and syntheses of new grafted materials for single site heterogeneous catalysis new insights in catalytic epoxidation and MPV reduction. FIG. 2 A is a closed Al(III) calixarene catalyst. FIG. 2B is an open A 1(111) calixarene catalyst.

[0023] FIG. 3 is a grafted Al(III)-calix[4]arene on silica for single site MPV catalysis.

[0024] FIG. 4 is a thermo-gravimetric Analysis of grafted closed Al(III) calix[4]arene sites.

[0025] FIG. 5 is a grafted Al(III)-calix[4]arene on silica for single site epoxidation.

[0026] FIG. 6 is a ²⁷ Al NMR of the open and closed Al(III) catalysts in solution. Both closed and open Al(III) calixarene species in solution indicates absence of catalytically unproductive octahedral (Oh) Al(III) sites.

[0027] FIG. 7 is a thermo-gravimetric analysis of grafted closed Al(III) calix[4]arene sites.

[0028] FIG. 8 is a first heterogeneous single-site MPV catalysis with Al(III). Covalent attachment of isopropoxy group on the Al center is an essential requirement for MPV catalysis. [0029] FIG. 9 is a Al(III)-calix[4]arene vs grafted Al(III)-isopropoxide for MPV reduction. Bulky calixarene ligand assists in the site-isolation and formation of productive active-sites for cataltic MPV reduction.

[0030] FIG. 10 is a ^!H NMR of MPV catalysis by open Al(III)-calixarene grafted complex.

[0031] FIG. 11 is a new synthetic route to anchored vanadium(V) calix[4]arene. Avoids use of reactive VC13 and subsequent oxidation step; use of milder condition avoids V(V) mediated dealkylation; 11% wt. loading of calix[4]arene showed by TGA; and potential catalyst for sulfoxidation.

[0032] FIG. 12 is a thermo-gravimetric analysis of grafted 1,3-dipropoxy V(V) calix[4]arene sites.

[0033] FIG. 13 is a ligand design and approaches in new material synthesis and catalysis.

[0034] FIG. 14 is a calixarene phosphinite, phosphonite and phosphites. Variables: (1) ring size; (2) density of functional groups; and (3) connectivities.

[0035] FIG. 15 is a preparation of chiral calix[4]arene phosphites and phosphate.

Presence of Lewis basicity, Bronsted acid and helicity of the diols offer a new platform for asymmetric catalysis.

[0036] FIG. 16 is a chiral induction through hemispherical cavity of calixarene based phosphite ligand: Asymmetric MPV reduction.

[0037] FIG. 17 is a library of surface anchorable chiral calix[4]arene phosphates. All three chiral calix[4]arene have been made and exists in desired cone conformations by ^!H NMR. BINOL and VANOL phosphates have been confirmed by HRMS, ³¹P NMR. Calix phosphate ligands did not work for catalytic asymmetric MPV reduction as phosphate groups can strongly coordinate to the Al.

[0038] FIG. 18 is a functional material synthesis.

[0039] FIG. 19 shows synthetic manipulations on ligand probing the steric and electronic sensitivities.

[0040] FIG. 20 shows relative reaction rate of substrates in probing ketone binding. [0041] FIG. 21 shows controlling Lewis-acid catalyzed MPV reduction and olefin epoxidation via synthesis of calixarene-metal complexes

DETAILED DESCRIPTION OF THE INVENTION

Introduction

[0042] The present invention provides, for the first time, organometallic coordination complexes formed between chiral phosphorus-containing calixarene-related ligands and metal atoms. The complexes provide a novel and unique tool for probing the properties of metal atoms complexed with chiral polyaromatic macrocycles, and access to an array of reactive metal compounds having reactivity and specificity tunable by varying the nature of the organic macrocyclic ligand component of the organometallic compounds. Also provided are phosphorus-containing calixarene-related molecules, which act as easily variable ligands, tunable to achieve a particular desired property in a metal atom coordinated to the ligand. Methods of making these ligands and coordinating them with metal atoms are also provided. Moreover, methods for making the organometallic compounds and methods for their use are also provided - in both their free and immobilized states.

[0043] Calixarene-related metal clusters and nanoparticles of this invention can be used to catalyze processes including those known in the art to be catalyzed by metal-mediated processes such as olefin rearrangements, hydroformylation of olefins, and cycloaddition of terminal alkanes, as well as other processes such as oxidation processes, hydrogenation processes, and acid-catalyzed reactions. In an exemplary embodiment, the composition of the invention is useful as a hydorprocessing catalyst.

Definitions

[0044] Calixarenes are cyclic oligomers of phenol and substituted phenols with formaldehyde, and are characterized by the general structure:

in which n is a value of 3-16, e.g., 3, 4, 6 or 8. General information about such molecules can be found, for example in Bauer et al., JACS 107, 6053 (1985) and the texts

"Calixarenes" by C. David Gutsche, which is part of the Monographs in Supramolecular Chemistry (J. Fraser Stoddart, ed.; Royal Society of Chemistry, 1989) and "Calixarenes Revisited" by the same author (1998).

[0045] Calixarenes are in the form of a cyclical oligomer having a "basket" shape, where the cavity can serve as a binding site for numerous guest species, including ions and molecules. The group R² may be hydrogen, or may be any of a number of aryl substituent groups including, but not limited to, alkyl, alkenyl, alkynyl, allyl, aryl, heteroaryl, alcohol, sulfonic acid, phosphine, phosphonate, phosphonic acid, thiol, ketone, aldehyde, ester, ether, amine, quaternary ammonium, imine, amide, imide, imido, nitro, carboxylic acid, disulfide, carbonate, isocyanate, carbodiimide, carboalkoxy, carbamate, acetal, ketal, boronate, cyanohydrin, hydrazone, oxime, oxazole, oxazoline, oxalane, hydrazide, enamine, sulfone, sulfide, sulfenyl and halogen. In exemplary calixarenes, R² typically represents a single substituent at the position para to the OR¹ group. However, calixarenes of use in the present invention can include one or more R substituent. When more than one substituent is present, the substituents can be the same or different. An exemplary class of calixarene compounds with two substituents is known in the art as the calix[n]resorcinarenes, which comprise resorcinol moieties that are joined to each other, and typically possess phenoxy groups in a different arrangement around the ring.

[0046] Exemplary R¹ substituents include H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl moieties comprising one or more coordinating atoms. In exemplary embodiments, 1 , 2 or 3 of the R¹ groups is a moiety derived from a diol and includes the group -P(0)₂R^P or -P(0)₂R^P (phosphate) in which R^p is an organic moiety derived from a chiral diol. In various embodiments, 1 or 2 of the R¹ groups is M, in which M is a metal atom. In various embodiments, 1 or 2 of the R¹ groups is M(L)_X, in which L is an organic ligand and x is 0, 1 , 2, 3, 4, 5, 6, or 7. In various embodiments, 1 or 2 of the R¹ groups is M(L)_X-Z in which Z is a substrate atom. In an exemplary embodiment, the substrate atom is silcon.

[0047] The term "calixarene-related compounds" is meant to include calixarenes and compounds similar to calixarene in that they contain aryl or heteroaryl groups linked by bridging moieties to form a "basket", as well as "basket"- type compounds formed by similarly linking other cyclic groups. The text "Calixarenes Revisited" (C. David Gutsche, Royal Society of Chemistry, 1998) describes some of these compounds, for instance on pp. 23-28, and this text is hereby incorporated herein. "Calixarene-related compounds" is meant to include the types of compounds mentioned in that text. It thus includes compounds referred to as "homocalixarenes", in which one or more bridges between the phenolic groups contain two or more carbon atoms. One example given in Gutsche is no. 62, which includes cyclobutyl bridges. In various embodiments according to the invention, calixarene-related compounds refers to chiral calixarenes including 1 , 2, or 3 chiral phosphorus-containing moieties bound to 1 , 2 or 3 oxygen atoms on the lower rim of the calixarene, metal complexes of these compounds and immobilized metal complexes of these compounds.

[0048] "Calixarene-related compounds" includes calixarenes and functionalized calixarene species, and also includes, for example, oxacalixarenes, azacalixarenes, silicacahxarenes and thiacalixarenes, which contain one or more oxygen, nitrogen, silicon or sulfur bridges, respectively, between phenolic groups, as well as calixarene compounds having one or more platinum bridges. This term also includes compounds such as those termed "calixarene-related cyclooligomers" in Gutsche (1998), for instance similar structures formed from furan or thiophene rather than phenolic residues. Other calixarene-related compounds include, for example, calix[n]pyrroles,

calix[m]pyridino[n]pyrroles or calix[m]pyridine. A "calix[n]pyrrole," is a macrocycle having "n" pyrrole rings linked in the a-positions. "Calix[m]pyridino[n]pyrroles" are macrocycles having "m" pyridine rings and "n" pyrrole rings linked in the a-positions. A "calix[m]pyridine" is a macrocycle having "m" pyridine rings linked in the a-positions.

[0049] The framework of the calixarene ligand can be substituted with other atoms that do not interfere with the ability of the ligand to form complexes with transition metals. For example, the framework of the calixarene ligand can be substituted with alkyl, aryl, halide, alkoxy, thioether, alkylsilyl, or other groups.

[0050] Exemplary calixarene -related compounds have four, six, or eight phenolic moieties; thus preferred calixarenes are calix[4]arenes, calix[6]arenes, and calix[8]arenes. Calix[4]arenes are more preferred. In preferred catalyst systems, the calixarene ligand is a p-alkylcalixarene, more preferably a p-t-butylcalixarene. The synthetic procedures for making these materials have been finely honed and optimized, and the starting materials, e.g., p-t-butylphenol, are readily available.

[0051] A "calixarene -related moiety" is a structure derived from a "calixarene -related compound or molecule" by its coordination to a metal cluster or nanoparticle, in an exemplary embodiment, through a linker comprising a coordinating atom.

[0052] A "coordinating atom" is a component of a calixarene, which coordinates with a metal atom of a metal atom in a compound of the invention. Exemplary "coordinating atoms" include nitrogen, oxygen, sulfur, phosphorus. The coordinating atom can be neutral or charged, e.g., a component of a salt or derived therefrom.

[0053] As referred to herein, an "organic ligand" is an organic moiety (e.g., selected from the groups defined hereinbelow) that is coordinated or otherwise bound to a metal in a compound of the invention. An organic ligand is generally a structure other than a calixarene.

[0054] The term "alkyl," by itself or as part of another substituent, means, unless otherwise stated, a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include di- and multivalent radicals, having the number of carbon atoms designated (i.e. Ci-Cio means one to ten carbons). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An

unsaturated alkyl group is one having one or more double bonds or triple bonds.

Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(l ,4-pentadienyl), ethynyl, 1 - and 3-propynyl, 3-butynyl, and the higher homologs and isomers. The term "alkyl," unless otherwise noted, is also meant to include those derivatives of alkyl defined in more detail below, such as "alkenyl", "alkylene" and "heteroalkyl" with the difference that the heteroalkyl group, in order to qualify as an alkyl group, is linked to the remainder of the molecule through a carbon atom. Alkyl groups that are limited to hydrocarbon groups are termed "homoalkyl".

[0055] The term "alkenyl" by itself or as part of another substituent is used in its conventional sense, and refers to a radical derived from an alkene, as exemplified, but not limited, by substituted or unsubstituted vinyl and substituted or unsubstituted propenyl. Typically, an alkenyl group will have from 1 to 24 carbon atoms, with those groups having from 1 to 10 carbon atoms being preferred.

[0056] The term "alkylene" by itself or as part of another substituent means a divalent radical derived from an alkane, as exemplified, but not limited, by -CH₂CH₂CH₂CH₂-, and further includes those groups described below as "heteroalkylene." Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the present invention. A "lower alkyl" or "lower alkylene" is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms.

[0057] The terms "alkoxy," "alkylamino" and "alkylthio" (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the remainder of the molecule via an oxygen atom, an amino group, or a sulfur atom, respectively.

[0058] The term "heteroalkyl," by itself or in combination with another term, means, unless otherwise stated, a stable straight or branched chain, or cyclic hydrocarbon radical, or combinations thereof, consisting of the stated number of carbon atoms and at least one heteroatom selected from the group consisting of O, N, Si, S, B and P and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Examples include, but are not limited to, -CH₂-CH₂-O-CH₃, - CH₂-CH₂-NH-CH₃, -CH₂-CH₂-N(CH₃)-CH₃, -CH₂-S-CH₂-CH₃, -CH₂-CH₂,-S(0)-CH₃, - CH₂-CH₂-S(0)₂-CH₃, -CH=CH-0-CH₃, -Si(CH₃)₃, -CH₂-CH=N-OCH₃, and CH=CH- N(CH₃)-CH₃. Up to two heteroatoms may be consecutive, such as, for example, -CH₂- NH-OCH₃ and -CH₂-0-Si(CH₃)₃. Similarly, the term "heteroalkylene" by itself or as part of another substituent means a divalent radical derived from heteroalkyl, as exemplified, but not limited by, -CH₂-CH₂-S-CH₂-CH₂- and CH₂-S-CH₂-CH₂-NH-CH₂-. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula CO₂R'- represents both C(0)OR' and

OC(0)R'.

[0059] The terms "cycloalkyl" and "heterocycloalkyl", by themselves or in

combination with other terms, represent, unless otherwise stated, cyclic versions of "alkyl" and "heteroalkyl", respectively. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. A "cycloalkyl" or "heterocycloalkyl" substituent may be attached to the remainder of the molecule directly or through a linker, wherein the linker is preferably alkylene. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, 1 -cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, l-(l ,2,5,6-tetrahydropyridyl), 1 -piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1 -piperazinyl, 2-piperazinyl, and the like.

[0060] The terms "halo" or "halogen," by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom.

Additionally, terms such as "haloalkyl," are meant to include monohaloalkyl and polyhaloalkyl. For example, the term "halo(Ci-C4)alkyl" is mean to include, but not be limited to, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.

[0061] The term "aryl" means, unless otherwise stated, a polyunsaturated, aromatic, substituent that can be a single ring or multiple rings (preferably from 1 to 3 rings), which are fused together or linked covalently. The term "heteroaryl" refers to aryl groups (or rings) that contain from one to four heteroatoms selected from N, O, S, Si and B, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. A heteroaryl group can be attached to the remainder of the molecule through a heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, 1 -naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3- pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4- oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2- pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1 - isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below.

[0062] For brevity, the term "aryl" when used in combination with other terms (e.g. , aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above. Thus, the term "arylalkyl" is meant to include those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(l- naphthyloxy)propyl, and the like).

[0063] Each of the above terms (e.g. , "alkyl," "heteroalkyl," "aryl" and "heteroaryl") are meant to include both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided below.

[0064] Substituents for the alkyl and heteroalkyl radicals (including those groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are generically referred to as "alkyl group substituents," and they can be one or more of a variety of groups selected from, but not limited to: substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, -OR', =0, =NR', =N-OR', - NR'R", -SR', -halogen, -SiR'R"R"', -OC(0)R', -C(0)R', -C0₂R', -CONR'R", - OC(0)NR'R", -NR"C(0)R', -NR'-C(0)NR"R"', -NR"C(0)₂R', -NR- C( R'R"R"')=NR"", -NR-C( R'R")=NR"', -S(0)R', -S(0)₂R', -S(0)₂NR'R", -NRS0₂R', -CN and -N0₂ in a number ranging from zero to (2m'+l), where m' is the total number of carbon atoms in such radical. R', R", R'" and R"" each preferably independently refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, e.g. , aryl substituted with 1 -3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups, or arylalkyl groups. When a compound of the invention includes more than one R group, for example, each of the R groups is independently selected as are each R', R", R'" and R"" groups when more than one of these groups is present. When R' and R" are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6-, or 7-membered ring. For example, -NR'R" is meant to include, but not be limited to, 1 -pyrrolidinyl and 4- morpholinyl. From the above discussion of substituents, one of skill in the art will understand that the term "alkyl" is meant to include groups including carbon atoms bound to groups other than hydrogen groups, such as haloalkyl (e.g., -CF₃ and -CH₂CF₃) and acyl (e.g. , -C(0)CH₃, -C(0)CF₃, -C(0)CH₂OCH₃, and the like).

[0065] Similar to the substituents described for the alkyl radical, substituents for the aryl and heteroaryl groups are generically referred to as "aryl group substituents." The substituents are selected from, for example: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, -OR', =0, =NR', =N-OR', -NR'R", -SR', -halogen, -SiR'R"R"', -OC(0)R', -C(0)R', -C0₂R', -CONR'R", -OC(0)NR'R", -NR"C(0)R',

-NR'-C(0)NR"R"', -NR"C(0)₂R', -NR-C(NR'R"R"')=NR"", -NR-C(NR'R")=NR"', - S(0)R', -S(0)₂R', -S(0)₂NR'R", -NRS0₂R', -CN and N0₂, -R', -N₃, -CH(Ph)₂, fluoro(Ci-C4)alkoxy, and fluoro(Ci-C4)alkyl, in a number ranging from zero to the total number of open valences on the aromatic ring system; and where R', R", R'" and R"" are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. When a compound of the invention includes more than one R group, for example, each of the R groups is independently selected as are each R', R", R'" and R"" groups when more than one of these groups is present.

[0066] Two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -T-C(0)-(CRR')_q-U-, wherein T and U are independently -NR-, -0-, -CRR'- or a single bond, and q is an integer of from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula A-(CH₂)_r-B-, wherein A and B are independently -CRR'-, -0-, -NR-, -S-, -S(O)-, -S(0)₂-, -S(0)₂NR'- or a single bond, and r is an integer of from 1 to 4. One of the single bonds of the new ring so formed may optionally be replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -(CRR')_s-X-(CR"R'")d-, where s and d are

independently integers of from 0 to 3, and X is -0-, -NR'-, -S-, -S(O)-, -S(0)₂-, or - S(0)₂NR'-. The substituents R, R', R" and R'" are preferably independently selected from hydrogen or substituted or unsubstituted (Ci-C6)alkyl.

[0067] As used herein, the term "acyl" describes a substituent containing a carbonyl residue, C(0)R. Exemplary species for R include H, halogen, substituted or

unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl.

[0068] As used herein, the term "fused ring system" means at least two rings, wherein each ring has at least 2 atoms in common with another ring. "Fused ring systems may include aromatic as well as non aromatic rings. Examples of "fused ring systems" are naphthalenes, indoles, quinolines, chromenes and the like.

[0069] As used herein, the term "heteroatom" includes oxygen (O), nitrogen (N), sulfur (S) and silicon (Si) and boron (B). [0070] The symbol "R" is a general abbreviation that represents a substituent group. Exemplary substituent groups include substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl groups.

[0071] The term "salt(s)" includes salts of the compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids, and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, butyric, maleic, malic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric,

methanesulfonic, and the like. Also included are salts of amino acids such as arginate, and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al, Journal of Pharmaceutical Science, 66: 1 -19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. Hydrates of the salts are also included.

[0072] Certain compounds of the present invention possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers and individual isomers are encompassed within the scope of the present invention. Optically active (R)- and (S)-isomers and d and / isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain olefmic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. Likewise, all tautomeric forms are included.

[0073] The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium (³H), iodine- 125 (¹²⁵I) or carbon- 14 (¹ C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention.

The Embodiments

[0074] The present invention provides novel chiral calixarene -related molecules and organometallic compounds comprised of calixarene-related moieties complexed with a metal. Moreover, there is provided a generalized approach for the synthesis of chiral calixarene-related moieties. In exemplary embodiments, the invention also provides a method of controlling aspects of the reactivity of metals by coordinating these metals with chiral calixarene-related moieties.

[0075] In an exemplary embodiment, the invention provides a chiral calixarene-related compound comprising one or more chiral phophite or phosphate moieties bound to the lower rim of the calixarene-related compound through a -0-P(0)₂R^p or -0-P(0)(0)₂R^p (phosphate) linkage in which R^p is the organic component of the ligand. Prior to the present invention, there were no examples of chiral calixarene phosphite and phosphate ligands formed through a -0-P(0)2R^p or -0-P(0)(0)2R^p (phosphate) linkage between a bidentate phosphine ligand and an oxygen of the lower rim of the calixarene.

[0076] Thus, in an exemplary aspect, the invention provides a chiral calixarene-related compound comprising, (a) a chiral organic ligand comprising phosphorus; (b) a calixarene-related moiety wherein said chiral organic species is bound to the lower rim of the calixarene-related compound through a -0-P(0)₂R^p or -0-P(0)(0)₂R^p (phosphate) linkage between a phosphine ligand derived from a chiral diol and an oxygen of the lower rim of the calixarene. R^p is the diol-derived chiral organic component of the ligand and in exemplary embodiments is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl moieties. In exemplary embodiments, the calixarene -related compounds of the invention include the phosphorus atom bound to 1 , 2 or 3 of the oxygen atoms of the lower rim of the calixarene -related compound.

[0077] In a further exemplary aspect, the invention provides an organometallic compound comprising a metal atom complexed to a chiral calixarene -related phosphite or phosphate compound described above. In an exemplary embodiment, the metal atom is coordinated through a single oxygen atom of the lower rim of the calixarene-related compound, and in another exemplary embodiment, the metal atom is coordinated to two oxygen atoms of this compound.

[0078] The present invention can be practiced with any metal atom that can coordinate with a coordinating atom on a linker component of a calixarene-related molecule.

[0079] This invention also relates to the immobilization of a metal atom coordinated to a chiral calixarene-related phosphite or phosphate compound described above on a substrate. In an exemplary embodiment, the metal atom is bound to the substrate. The metal atom can be bound first to a substrate and subsequently complexed to a calixarene or the metal atom complexed to the calixarene-related compound can be bound to the substrate. Alternatively, the metal cluster/nanoparticle can be contacted with a substrate to which a calixarene-related moiety is bound, thereby forming the immobilized complex. Methods of tethering calixarenes to surfaces are generally known in the art. See, for example, U.S. Pat. Appl. Pub. No. 2005/0255332.

[0080] Exemplary substrate components include, but are not limited to metals, inorganic oxides, glasses and polymers. A non-limiting list of useful substrates includes, silicon, tungsten, niobium, titanium, zirconium, manganese, vanadium, chromium, tantalum, aluminum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron. Metal oxides and zeolites (intact and delaminated) are exemplary substrates of use in conjunction with the compounds of the invention.

[0081] In an exemplary embodiment, the substrate is an inorganic oxide. In this embodiment, an exemplary immobilization process includes contacting the metal coordinated to the calixarene-related compound with a substrate. The substrate is optionally surface-modified by reaction with one or more polyhalides and/or

[0082] Metals are also of use as susbstrates in the present invention. Exemplary metals of use in the present invention as substrates include, but are not limited to, gold, silver, platinum, palladium, nickel and copper. In one embodiment, more than one metal is used. The more than one metal can be present as an alloy or they can be formed into a layered "sandwich" structure, or they can be laterally adjacent to one another.

[0083] Organic polymers are a useful class of substrate materials. Organic polymers useful as substrates in the present invention include polymers which are permeable to gases, liquids and molecules in solution. Other useful polymers are those which are impermeable to one or more of these same classes of compounds.

[0084] Organic polymers that form useful substrates include, for example, polyalkenes (e.g., polyethylene, polyisobutene, polybutadiene), polyacrylics (e.g., polyacrylate, polymethyl methacrylate, polycyanoacrylate), polyvinyls (e.g., polyvinyl alcohol, polyvinyl acetate, polyvinyl butyral, polyvinyl chloride), polystyrenes, polycarbonates, polyesters, polyurethanes, polyamides, polyimides, polysulfone, polysiloxanes, polyheterocycles, cellulose derivative (e.g., methyl cellulose, cellulose acetate, nitrocellulose), polysilanes, fluorinated polymers, epoxies, polyetters and phenolic resins. See, Cognard, J. ALIGNMENT OF NEMATIC LIQUID CRYSTALS AND THEIR MIXTURES, in Mol. Cryst. Liq. Cryst. 1: 1-74 (1982). Presently preferred organic polymers include polydimethylsiloxane, polyethylene, polyacrylonitrile, cellulosic materials,

polycarbonates and polyvinyl pyridinium.

[0085] The surface of a substrate of use in practicing the present invention can be smooth, rough and/or patterned. The surface can be engineered by the use of mechanical and/or chemical techniques. For example, the surface can be roughened or patterned by rubbing, etching, grooving, stretching, and the oblique deposition of metal films. The substrate can be patterned using techniques such as photolithography (Kleinfield et al, J. Neurosci. 8: 4098-120 (1998)), photoetching, chemical etching and microcontact printing (Kumar et al, Langmuir 10: 1498-51 1 (1994)). Other techniques for forming patterns on a substrate will be readily apparent to those of skill in the art.

[0086] The size and complexity of the pattern on the substrate is controlled by the resolution of the technique utilized and the purpose for which the pattern is intended. For example, using microcontact printing, features as small as 200 nm have been layered onto a substrate. See, Xia et al., J. Am. Chem. Soc. 117: 3274-75 (1995). Similarly, using photolithography, patterns with features as small as 1 μπι have been produced. See, Hickman et al, J. Vac. Sci. Techno!. 12: 607-16 (1994). Patterns that are useful in the present invention include those which comprise features such as wells, enclosures, partitions, recesses, inlets, outlets, channels, troughs, diffraction gratings and the like.

[0087] Using recognized techniques, substrates with patterns having regions of different chemical characteristics can be produced. Thus, for example, an array of adjacent, isolated features is created by varying the hydrophobicity/hydrophilicity, charge or other chemical characteristic of a pattern constituent. For example, hydrophilic compounds can be confined to individual hydrophilic features by patterning "walls" between the adjacent features using hydrophobic materials. Similarly, positively or negatively charged compounds can be confined to features having "walls" made of compounds with charges similar to those of the confined compounds. Similar substrate configurations are also accessible through microprinting a layer with the desired characteristics directly onto the substrate. See, Mrkish,et al., Ann. Rev. Biophys. Biomol. Struct. 25:55-78 (1996). [0088] In various exemplary embodiments, the substrate is a zeolite or zeolite-like material. In one embodiment, the complexes of the invention are attached to a substrate by the surface functionalization of ITQ-2-type layered and zeolitic materials. An exemplary attachment is effected via ammoniation of the substrate. The invention provides such functionalized materials covalently-bound to calixarenes. In an exemplary embodiment, the functionalized surfaces will are used to nucleate and grow metal nanoparticles on the surface of the material.

[0089] Calixarene-related compounds can be immobilized onto silica or other substrates as mentioned above without the need for synthetic derivatization with flexible linker groups that contain carbon, sulfur etc, atoms. The resulting immobilized calixarenes and related compounds possess lipophilic cavities that can be accessed with gas physisorption experiments at cryogenic temperatures, as well as with neutral organic molecules at room temperature. Phenol and nitrobenzene adsorb reversibly from aqueous solution within this class of materials.

[0090] The invention also includes methods of utilizing the calixarene-related moiety complexed metal atom of the invention in various chemical processes. An exemplary process is catalysis. The compositions of the invention are useful as catalysts in a number of processes including, without limitation, hydrogenation, hydride shift (e.g., Meerwein-Ponndorf-Verley), carbonylation of organic substrates, e.g., carbonylation of methane to form acetic acid, epoxidation.

[0091] Calixarene-related compounds of the invention can be synthesized by methods within the abilities of those of skill in the art. Exemplary syntheses are set forth herein, however, it will be apparent to those of skill that additional practical synthetic pathways exist and can be devised. Accordingly, the present invention is not limited to the use of a calixarene-related compound synthesized by any particular method.

[0092] Exemplary routes to calixarene-related compounds of the invention are set forth in the figures and examples appended hereto.

[0093] The present invention provides compounds in which a calixarene-related moiety is complexed to a metal atom. It is well within the ability of those of skill in the art to choose a particular combination of coordinating atom on a calixarene-related compound of the invention and metal atom to provide a coordinating atom that binds to the metal atom.

[0094] One exemplary embodiment of this invention is the use of a silica substrate to which the calixarene-related compound/moiety are immobilized via silica-metal atom bonds. However, as previously discussed, the substrate and/or the modifying agent may be an oxide, halide, alkyl or alkoxide of another element. The modifying agents may contain the same element as the primary element on the substrate (e.g. aluminum alkoxides used to modify an aluminum oxide substrate) or they may contain different elements (e.g. silicon tetrahalide used to modify an aluminum oxide substrate). When alkoxides are used in this invention, the substrate-modifying element of the alkoxide (silicon, another non-metal, or a metal) becomes bonded directly to phenolic oxygen atoms of the calixarene, and an alcohol corresponding to the alkoxide is split off.

Preferred alkoxides used as substrate modifiers in this invention include methoxides, ethoxides and other alkoxides having up to four carbon atoms per alkoxide group.

[0095] In various embodiments, the invention provides a chiral calixarene-related compound having the formula:

wherein R^a, R^b R^c, and R^d are independently selected "aryl group substituents". The symbols R^pl and R^p2 independently represent substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl moieties. In an exemplary embodiment, these groups are derived from the corresponding aryl or heteroaryl diol, which is optionally further substituted with one or more "aryl group substituents". The group R³ is H, - P(0)₂-R^p3, M(L)_X, or M(L)_X-Z, wherein R^p3 is an aryl or heteroaryl moiety, optionally derived from the corresponding diol and optionally further substituted with one or more "aryl group substituent". L is an organic ligand. The index x is 0, 1 , 2,3, 4, 5, 6, or 7. Z is a substrate atom, and R⁴ is H or is a bond to M, when R³ is M(L)_X. Thus, the calixarene -related compounds of the invention can form open (R⁴ is H) or closed (R⁴ is a bond to the metal) structures. Where is -P(0)2-R^p3 is designated, this group can also be or -0-P(0)(0)2R^p (phosphate), as can the phosphorus atom attached to the oxygens of the ring structures containing R^pl and R^p2.

[0096] The following examples are provided by way of illustration only and not by way of limitation. Those skilled in the field will readily recognize a variety of noncritical parameters that could be changed or modified to yield essentially similar results.

EXAMPLES

Preparation of Calix[4]arene BINOL phosphite ligand:

[0097] In a 250 mL round bottom flask equipped with magnetic stirrer calix[4]arene (650 mg, 1 mmol, 1 equiv) was taken with 50 mL freshly distilled toluene (refluxed over sodium). To the reaction flask (R)-(-)-4-chlorodinaphthol[2,l -d: Γ,2'- f][l ,3,2]dioxaphosphepin (710 mg, 2.03 mmol, 1.02 equiv) is added. To this flask freshly 50 mL of distilled pyridine (refluxed over Ca¾) was added. The reaction mixture was refluxed for 2 hours and then kept stirring for overnight (16 h). ³¹P monitoring of the reaction indicated 100% conversion of the starting chlorophosphite into the desired product.

[0098] The crude product was concentrated under vacuum and was

chromatographically purified on silica gel (with 5% acetonitrile in benzene as eluent) to isolate bisphosphite calix[4]arene 210 mg calix[4]arene bisphosphite (16% ).

[0099] ³¹P NMR of this purified product (1) shows single peak at 115 ppm and the ^!H NMR (in CDCls): 7-8 ppm (m, 32 H), 4.5 ppm (d, 2H), 4.35 (d, 2H), 3.65 (d, 2H), 3.45 (d, 2H), 1.55 (s, 9H), 1.45 (s, 18H), 1.2 (s, 9H). ESI-MS shows molecular ion peak (m/z = 1276.52+ Na)

[0100] In identical procedure as above chiral BINOL calix[4]arene bis phosphate is prepared:

³¹P, ¾ ¹³C and HRMS data are obtained for this compound (2).

[0101] Other ligands prepared by this method include:

Catalytic asymmetric MPV reduction:

[0102] In a 50 ml rb flask calix[4]arene phosphite ligand (1) (128 mg, 0.1 mmol, 10 mol% equiv) was taken in 10 mL CH₂CI₂ (anhydrous, distilled over Ca¾). To this flask 2(M) Me₃Al solution in heptane is injected (0.1 mmol, 10 mol %). Upon stirring for 10 minutes 300 |iL of 2-propanol was injected (4 mmol, 4 equiv), followed by addition of ortho fluorobenzophenone (200 mg, 1 mmol, 1 equiv.) and the reaction mixture was cooled to 0°C. The ee monitoring of the reaction by chiral GC showed more than 99% ee in lh at 0°C (TOF = 10^"4). This is the highest ee ever measured for this reaction.

Heterogeneous MPV Catalysis:

[0103] Grafted Calix[4]arene Aluminum complex on silica was shown to be active for catalytic MPV reduction: The acivity (turn over frequency) of heterogeneous catalyst A was almost identical to that of the homogeneous MPV reduction shown below. This confirms that the catalytically active sites in Catalyst A are as accessible as in homogeneous MPV reduction and are of single site in nature.

2-propanol, 6h 83% conv

Homogeneous MPV reduction:

n

[0104] A ligand (4) that is isostmctural to ligand 3 prepared for use in heterogeneous MPV catalysis.

Synthesis of Ligand 4:

[0105] In a 250 mL rb flask equipped with a magnetic stirrer lmmol of calix[4]arene in toluene was taken and warmed to 80 °C. A clear solution was obtained and the reaction flask was brought back to rt. To this flask NaH in oil (60% by weight) (125 mg, 3.1 mmol, 3.1 equiv) was added. A solution of (R)-(-)-4-chlorodinaphthol[2,l-d: l',2'- f][l ,3,2]dioxaphosphepin in toluene ( l . l g, 3.1 mmol, 3.1 equiv) was added. To drive the reaction (0.6 g, 3 mmol, 3 eq.) of 2,6-di-tert butylpyridine was added. The reaction was monitored by 3 IP NMR. Near complete conversion to desried ligand 3 was observed by ³¹P NMR monitoring of the reaction.

[0106] Upon purifying the ligand by silica gel column chromatography -120 mg of 3

1 31

was obtained that was characterized by H and P NMR and also by 2-dimensional NMR techniques to prove the that all of the structure 3 exists in cone conformation.

Catalyst B

[0107] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.

[0108] All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

Claims

WHAT IS CLAIMED IS:

1. A chiral calixarene-related compound comprising 1 , 2, or 3 chiral phosphite or phosphate ligands bound to a lower rim oxygen atom of the calixarene-related compound through a -0-P(0)₂R^p or -0-P(0)(0)₂R^p linkage, in which R^p is the organic component of the ligand wherein in at least one lower rim oxygen is OH .

2. The chiral cahxarene according to claim 1, wherein R^p(0)₂ is derived from a chiral diol.

3. The chiral calixarene-related compound according to claim 2 wherein the chiral diol is a substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl diol.

4. The chiral calixarene-related compound according to claim 1, wherein at least one of the lower rim oxygen atoms is bound to a metal atom.

5. The chiral calixarene-related compound according to claim 4, wherein the metal atom is Al.

6. The chiral calixarene-related compound according to claim 1 wherein said

compound catalyzed Meerwein-Ponndorf-Verley hydride transfer.

7. The chiral calixarene-related compound according to claim 6 wherein said

hydride transfer occurs with at least about 60% ee.

8. The chiral calixarene-related compound according to claim 7, wherein said

hydride transfer occurs with at least about 75% ee.

9. The chiral calixarene-related compound according to claim 4, wherein said

compound is immobilized on a substrate.

10. The chiral calixarene-related compound according to claim 9, wherein said

compound is immobilized to a substrate through the metal atom.

11. The chiral calixarene-related compound according to claim 1 having the formula:

wherein

R^a, R^b R^c, and R^d are independently selected aryl group substituents;

R^pl and R^p2 are independently selected aryl or heteroaryl moieties derived from the corresponding diol;

R³ is a member selected from -P(0)₂-R^p3 , -0-P(0)(0)₂R^p, M(L)_X, and M(L)_X-Z wherein

R^p3 is an aryl or heteroaryl moiety derived from the corresponding diol; L is an organic ligand;

x is 0, 1 , 2,3, 4, 5, 6, or 7; and

Z is a substrate atom;

R⁴ is a member selected from H and a bond to M when R³ is M(L)_X.

12. The chiral calixarene-related compound of claim 11, wherein M is Al.