Reprinted I'rom The Journal of Organic ('hemistry, 1981,'16, 2861. Copyright O 1981by the American Chemical Society and reprinted by permissionof the copyright owner Synthesis of Functional Chelating Diphosphines Containing the Bis[2-(diphenylphosphino)ethyl]aminoMoiety and the Use of These Materials in the Preparation of Water-Soluble Diphosphine Complexesof Transition Metalsr Ralph G. Nuzzo, Sharon L. Haynie, Michael E. Wilson, and GeorgeM. Whitesides* Department of Chemistry, MassachusettsInstitute of Technology,Carnbridge, Massachusetts 02139 ReceiuedMarch 19. 1981 Acylation of bis[2-(diphenylphosphino)ethyl]amine provides a flexible synthesis of functionalized chelating diphosphines. This t.uitiott off"rs a route to diphosphine complexes of transition metals having a wide r?n-ge of structures and physical properties and especiallyto water-soluble complexes. The aqueoussolubility of the free ligands and of ttre compleres prepared from them depend on the ligand, on the metal, and on other materials (especially surfactants) present in the solution. We describe typical preparations of ligands and outline the properties of their complexes with certain transition metals. Homogeneous catalysis and asymmetric synthesis in- functionalized, water-soluble,chelating diphosphines and creasingly require complex organic structures incorporating presented examples of applications of these materials. ligands capable of coordinating a transition-metal center. This paper provides experimental proceduresfor these In earlier papers,2-awe described a flexible synthesisof synthesesand outlines factors affecting the properties of the resulting materials in aqueous solutions. (1) Supported by the National Science Foundation (Grants Results and Discussion 77LL282CHE and8012722-CHE). R.G.N. held a predoctoral traineeship from the National Cancer Institute (CA 09112CT) and S.L.H. an HEW All synthesesare basedon bisl2-(diphenylphosphino)- predoctoral fellowship. ethyllamine 1 (SchemeI).5 This compound, isolated as (2) Wilson, M. E.; Whitesides,G. M. Arn. Chem. Soc.1978,100, "/. air-stable hydrochloride' can be acylated at 306-307. a crystalline, (3) Wilson, M.E.; Nuzzo,R. G.;Whitesides,G. M. J. Am. Chem. Soc. 1978, 100,2269-2270. (4) Nuzzo, R. G.; Feitler, D.; Whitesides,G. M. J. Am. Chem. Soc. (5) Compound 1 was first prepared by: Sacconi, L.; Marassi, R. J. 1979, 101,3683-3685. Chem. Soc. A 1968,2997-3002. 2862 J. Org.Chem., Vol. 46, No. 14, 1981 \r.rz-zr,€t al Scheme I. Preparation of Bis[2-(diphenylphosphino )ethyl]amine and Derivatives -.- ,.4", wl l) 2 Ph2Pfl .Apph^ cl'' H^N'z''a--rct - (cH--[coKJHF* t' t.tr. ,rn. 2) HCI r I o -4=4 I ll l0 I \-z:( 'b I o-- i I 4 i o I /-1,'PPhz I /1pp,""2 !-7.=y/(J \ n AY';r1 \-//PPhz or)',) \-''PPhz oiY/1po- . -h? .\ 4"", - ^-/( N' -" 'r--,rPPh, l o O 5 5, i I , Nuc, Nuc: I t O0 0 'oF\ xo$'r-^.tr,,- n'1PPh. o 'PPh2 u,,\1\2 . /PPh, tlrcfA _,.r(- 0 1----'PPh' Y nitrogen without competingreaction at phosphorus. The groups.These groups can be designedto conferthe desired ability to functionalizenitrogen selectively,inthe presence physicalpropertres to the final complex. of the phosphinecenters is the basisfor a method for the An alternativestrategy, direct ac1'lation of 1 te.g..I + incorporationof I into complex organicstructures. 7) is also suc'c'essful.Although this procedureappears The reactivity of I toward acid chlorides,anhl'drides, simpler.in practicewe havefound it to be lessuseful than isocyanates,alkyl chlorocarbonates.and .\'-hvdroxl'- I - 5 - 8 or I -. 6 -* 9 as a method for generating succinimide (NHS) active estersis that erpected for a functionalized (especiallywater soluble) diphosphines. stericallyhindered, secondary amine. Theserea('tions go The number of readily availablereactive species of the trpe to completionat ambient temperatures(the time necessarv representedby 4 (that is, specieswhich react selectivell' for reactiondepends both on the couplinggroup empkrl'ed with nitrogen in the presenceof phosphorusand w'hich and on the nature of additionalbases present in solution; introducehighly polar groups)is small. Bv contrast.2 is see Experimental Section). Little or no competing re- commerciallyavailable and inexpensive,and 5 react-sn'ith activity is observedfor the phosphinegroups. Onlv in the a wide range of amines. In applicationsin n'hich rl'ater casesof materials capableof reactionsother than acylation solubility is not an important objective.hon'ever. direct do competing reactionsbecome important: specialcare acylation can provide a convenientand useful methodolog'u' must be exercisedin usingthese coupling agenLs. Acryloyl (vide infra). chloride can be used to acylate I under the conditions Table I lists the substancesprepared. the coupling describedbelow. All attempts to acylate I with maleic agentsused in their preparation,and the vields in which anhydride gaveonly air-sensitive,red gums: although some they wereobt.ained. The purification and characterization amide formation is apparent in the IR spectra of the re- of these complexesproved difficult. Manl' have surfactant action mixtures, we have been unable to isolate a useful properties;their polar functionalities are hydrated or derivative of I from these mixtures. Soft electrophiles solvated to varying extents; they are noncrystaliine. (sulfonyl chlorides,cyanogen bromide, phosphoryi halides) Characterizationoften was basedprimarily on IR and 31P also seem not to demonstrate the selectivity toward ni- and lH NMR spectroscopiesand on the physical properties trogen required to achieve useful functionalization. (water solubility, abilit5,'to complexmetals) of the com- The most useful synthetic strategy to emergefrom this pounds. Only compounds10, 12, 13, 15, 17,2l,and 22 were work used a diacylating reagent [trimellitic anhydride acid isolated in a form sufficiently pure to give acceptableel- chloride (2) or tricarballylic anhydride acid chloride (3)l emental analyses.Analytical data for others are included to couple I to another amine-containing group which in the ExperimentalSection, as an aid in judging purity. conferredthe physical properties required. Thus, for ex- Yields given in parenthesesin Table I are for crude com- ample, reaction of 1 with 2 proceedscleanly at the more pounds and are upper limits. reactive acid chloride site and generates5. The effect of The proton NMR spectra of a number of the water- this transformation is to convert 1 (in which functionali- solublederivatives (17-20) in aqueoussolution show broad, zation is based on the difference between the nucleo- complexresonances. suggesting micelle formation, although philicity of the nitrogen and phosphoruscenters) to 5 (in the presenceof aggregatedstructures was not rigorously which functionalization can be basedon the electrophilic established.The 31PNMR spectraof the free ligandsare anhydride group, without competition from the phosphine usuallycharacterized by'two linescentered at -1.5 ppm. centers). Compound 5 (and the analogous6) is not isolated Control experimentsdemonstrated that the splitting occ\us but is allowed to react directly with other nucleophilic on acylation;we a^ssumethat it reflects slow rotation about Functional Chelating Diphosphines J. Org.Chem., Vol. 46, No. 14, 1981 2863 Table I. Functionalized Diphosphines from L having 7 as a ligand.6'7 Of the severalmetals examined - lNP, N(CHrCHrPPhr)rl in this study, the cationic rhodium complexeswere the reacting yield,o most soltrblein water. compd group % The aqueoussolubility of the free ligands seemsto follow expectedtrends. The doubly chargedspecies 17, 18,and o o ,/"-1 20 are much more soluble than singly chargedmaterials (Yn" Ip \y'so.Ho \.^,Ss^ such as 7, 16, and 19. The neutral polyethyleneglycol o sy'steml1 shows increasingsolubility with increasing '(\' RCONHS = 11O molecularweight: at n 110the material appearsto be ( s)--.-,-.r,/(Np. completelysoluble. In this sameseries similar changes I rverenoted in the solubility of 11.PtCl2complexes. c Hr( ocHzcH 2)n O C NP2 ROCOCI n. 2,6, ltO HomogeneousCatalysis by Cationic Rhodium Com- 'f plexes. he Rh(I) complexesof severalof theseligands Ph NHC NPz RNCO 93 have been shown to act as effective homogeneoushydro- J genation c'atalystsin aqueoussolution for a range of r3 .ltt.o, 4coHe, Anhydr ith w'ater-solublesubstrates.a The data presentedbelow ex- HPlP. pand Llponearlier observations.a t4 o\r?o In general,the most solublecomplexes acted as the best Anhy dri dc (e.g., 4' OMe'n catalvsts. Catalyststhat precipitated from solution l6.Rh(l )) saveunderstandably low rates of hydrogenation t5 c H3coN P2 RCOC rr.ithtr-acetamidoacrylic acid (turnover number = TN < i mol of olefin reduced/mol of rhodium complex/h). 16 xo.c'.r/\ne. A nhtd rr da Solubilitv is, however,not the only requirementfor high ac'tivitl'sincell.Rh(I) (a = 16, 110)was a poor catalyst O HOt\,--\y Np_ despiteits reasonablyhigh solubility in water. The com- t7 lz5 aac* pler 7.Rh(I) was sparinglysoluble and had low activity. o ro oI1\7irc, Since7 is extremelysoluble, we infer that coordinationof 18 *0.t, 3 -aTf/ _--,-] the sulfonicacid group to rhodium resultsin this decrease 0- in ,solubilityand activity.8 In our hands,rhodium com- xoir, o rs 6 plexesof l7 and 18 formed the catalystshaving the highest /Yf--Ant lo For reasons, \NHCO(CHOH)4CH2OH activitl'. several we believe that the best material for most applications in homogeneoushydro- 0 no{--\ genationis 17.Rh(I). First, unlike most of theseligands, ?o Noo.s 6 J ;"i'lr,/'-\./^Npz -t - purified. \ 7, 17 is highly crystallineand is easily Second,the o protonated form of the acid is soluble in a wide range of o_0 /-\ il ?t Hf Rcocl organic solvents,a feature attractive for catalyst prepa- il\ /)-cNP2 42 o- ration. Dissolution in water is easily accomplished by L1-\ I transferring the catalyst preparation in a water-miscible P2Nc{'>cNP2 w organic solvent such as acetone,under argon, into the reactionmedia. In this manner,the number of manipu- ?3 Ph.P (CH.CH.O) RCi rMe lations necessaryto prepare the catalyst can be minimized. Third, the synthesisof 17 is simple and can be easily 24 -r'-\(Npz Rcocl ,9a 1 carried out on practical scales:routine preparationsgave o? more than 10 g of purified material in nearly quantitative '-i.?l yield.