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Download Author Version (PDF) Dalton Transactions Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/dalton Page 1 of 39 Dalton Transactions Chiral multidentate oxazoline ligands based on cyclophosphazene cores: Synthesis, characterization and complexation studies Dheeraj Kumar, Jatinder Singh and Anil J. Elias ,* ____________________________________________________________________ Chiral oxazoline based bi and hexadentate ligands built on cyclophosphazene cores have been synthesized and characterized. (NPPh 2)2[NP(m-OC 6H4C(O)OCH 3)2] (1) was prepared by the reaction of gem -(NPPh 2)2(NPCl 2) with methyl-3-hydroxy benzoate in presence of Cs 2CO 3. Compound 1 was converted to the dicarboxylic acid (NPPh 2)2[NP(m-OC 6H4C(O)OH)2] (2) Manuscript using base promoted hydrolysis with KO(t-Bu). The dicarboxylic acid 2 on reaction with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol, triethylamine and mesyl chloride was converted to the C 2- symmetric phosphazene based chiral bisoxazoline ligand (NPPh 2)2[NP{m- OC 6H4(4-iPr-2-Ox)}2] (3) (Ox = oxazolinyl). A similar C2-symmetric bisoxazoline derivative Accepted having oxazoline group attached to the para position of the phenyl ring was also synthesized starting from (NPPh 2)2[NP(p-OC 6H4C(O)OCH 3)2] (4) which was first converted to the dicarboxylic acid (NPPh 2)2[NP(p-OC 6H4C(O)OH) 2] (5) and finally to (NPPh 2)2[NP{p-OC 6H4(4- iPr-2-Ox)}2] ( 6) and (NPPh 2)2[NP{p-OC 6H4(4-Ph-2-Ox)}2] (7) under similar reaction conditions. Reaction of 6 with Pd(OAc) 2 in acetic acid at room temperature and with PdCl 2(C 6H5CN) 2 in Transactions ________________________________________________________________________ Department of Chemistry, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India . E-mail: [email protected] FAX : +91-11-26581102; Tel: +91-11-26591504. Dalton †Electronic supplementary information (ESI) available: CCDC reference numbers 1007180-1007186. Selected bond distances and angles of compounds 1, 2, 4, 5, 7, 14 and 18 . For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/b000000x/ 1 Dalton Transactions Page 2 of 39 refluxing benzene resulted in chiral palladium complexes Pd(OAc) 2(NPPh 2)2[NP{p-OC 6H4(4- iPr-2-Ox)}2] ( 8) and PdCl 2(NPPh 2)2[NP{p-OC 6H4(4-iPr-2-Ox)}2] (9), respectively. The utility of these palladium complexes as chiral catalysts for the asymmetric rearrangement of trichloroacetimidates to trichloroacetamides has been explored. Hexa(methylbenzoate) derivative of cyclophosphazene [PN(OC 6H4COOCH 3)2]3 (10 ) on treatment with KO(t-Bu) and H 2O gave the hexacarboxylic acid derivative [PN(OC 6H4COOH) 2]3 (11 ), which on treatment with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl chloride was converted to the C 3-symmetric cyclophosphazene based Manuscript chiral hexaoxazoline ligands [PN{OC 6H4(4-iPr-2-Ox)}2]3 (12), and [PN{OC 6H4(4-Ph-2-Ox)}2]3 (13 ). Bis(Phebox) derivative of the cyclophosphazene was prepared starting from (NPPh 2)2[NP{OC 6H3(COOCH 3)2}2] (14) , by the reaction of gem -Ph 4P3N3Cl 2 with dimethyl 5- hydroxyisophthalate in presence of Cs 2CO 3. Compound 14 was converted to the tetracarboxylic Accepted acid (NPPh 2)2[NP{OC 6H3(COOH)2}2] (15 ) using base promoted hydrolysis with KO(t-Bu). The tetracarboxylic acid 15 on reaction with oxalyl chloride followed by (S)-(+)-2-amino-3- methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl chloride was converted to the bis(Phebox) substituted tetraphenylcyclophosphazene derivatives (NPPh 2)2[NP{OC 6H3(4- iPr-2-Ox) 2}2] (16)/ (NPPh 2)2[NP{OC 6H3(4-Ph-2-Ox) 2}2] (17). A similar tetra(phebox) derivative was synthesized from (NPPh )[NP{OC H (COOCH ) } ] (18) which was first 2 6 3 3 2 2 2 Transactions converted to (NPPh 2)[NP{OC 6H3(COOH)2}2]2 (19) and further converted to the tetra(phebox) derivative (NPPh 2) [NP{OC 6H3(4-Ph-2-Ox) 2}2]2 (20) . All new compounds were characterized by 1 13 1 31 1 IR, NMR [ H, C{ H} and P{ H}] and HRMS studies. Compounds 1, 2, 4, 5, 7, 14 and 18 Dalton have also been structurally characterized. KEYWORDS: cyclophosphazenes, multidentate, oxazoline, chiral, palladium, Phebox. 2 Page 3 of 39 Dalton Transactions Introduction Six membered cyclophosphazene rings provide an elegant platform for building multidentate ligands having a stable core with or without the ring nitrogen’s providing additional ligating sites.1-3 The out of plane directionality of the cyclophosphazene ring substituents has also assisted in the design of a range of stable dendrimers 4 and multiporphyrin assemblies. 5 It is surprising to note that in spite of a wide range of possibilities, very few phosphazene based multidentate ligands are known in the field of asymmetric catalysis.6,7 Various groups have tried to explore the chirality possible on the phosphazene ring by selective ring substitution studies Manuscript focusing on the stereogenic property of tetracoordinated phosphorus atoms in cyclophosphazenes, following up the same by changes observed in the 31 P NMR spectra and by using HPLC techniques. 8 However, from an applied perspective, except a few which have multi- ligating sites and clearly display specific rotation of plane polarized light, most of these Accepted derivatives do not show promise as chiral ligands in asymmetric catalysis. In contrast, cyclophosphazene based dendrimers which contains chiral ferrocene based Josiphos units at the periphery have been found to be useful ligands in Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate. 7 Compounds containing chiral 2-oxazoline rings are widely used in asymmetric catalysis due to their ease of synthesis and effectiveness for diverse type of catalytic transformations.9 Transactions Bis(oxazoline) ligands are among the most valuable class of oxazoline ligands from their ability to coordinate with a wide range of metals and due to the presence of C 2- axis in the resulting complexes, which is proven to be beneficial in controlling the enantioselectivity by reduction of Dalton possible transition states having square planar geometry. 10 Reports are available on trisoxazoline derived metal complexes being used as catalyst for Friedel-Crafts, Kinugasa 1,3-dipolar cycloaddition, cyclopropanation, Diels-Alder reaction and also for chiral recognition with good 3 Dalton Transactions Page 4 of 39 selectivity. 11 It has been observed that in general, multi-oxazoline ligand bound metal complexes have advantages such as better catalyst stability, tunable chiral space and increased ligand diversity resulting in better enantifocal control, broader substrate scope, as well as better enantioselectivity under milder reaction conditions. 12 Although a few examples of mono, bis and hexa-oxazoline substituted cyclophosphazenes are known in the literature, 13 they are not suitable for asymmetric catalysis as most of them are achiral and those having chiral oxazoline groups are having the chiral centre adjacent to the oxygen atom of the oxazoline ring. It is known that oxazoline rings having chiral centre adjacent to its nitrogen atom are preferred in the asymmetric Manuscript catalysis as the metal is held closer to the chiral centres strongly influencing the enantioselectivity. 9 Herein we report the first examples of chiral bis and hexa-oxazoline as well as multiphebox derivatives of cyclophosphazenes having the chiral center close to the nitrogen atom of the oxazoline ring. We have also explored the complexation behavior of few of these Accepted ligands with Pd(OAc) 2 and PdCl 2(C 6H5CN) 2, and explored their possible utility in asymmetric catalysis. The new multi-oxazoline ligands having a cyclophosphazene core show promise for catalyzing many organic transformations and for chiral recognition. Results and Discussion Transactions Hexachlorocyclotriphosphazene contains both a C3- axis (passing through the center of the P 3N3 ring perpendicular to the ring plane) and three C 2- axes (passing through the ring phosphorus atom and its opposite ring nitrogen atom) (Figure 1). Therefore the ring can act as an excellent precursor Dalton for preparing multioxazoline ligands having C 2 and C 3 axis, which can play a critical role in determining the enantioselectivity of a catalytic reaction. 4 Page 5 of 39 Dalton Transactions C3 C2 Cl Cl P N Cl N P Cl Cl PN Cl Fig. 1 C3- and C 2- axis present in the cyclophosphazene ring. Manuscript Various ester derivatives of cyclophosphazenes (P 3N3Cl 6, gem -Ph 4P3N3Cl 2 and gem - Ph 2P3N3Cl 4) were prepared by the reactions of their P-Cl bonds with methyl-3-hydroxy benzoate/methyl-4-hydroxy benzoate/dimethyl 5-hydroxyisophthalate in the presence of Cs 2CO 3 in the molar ratio 1:1:2.
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