Solvent-free isomerization of allylic alcohols catalyzed by a rhodium catalyst-organic framework

Abstract

The solvent-free isomerization of allylic alcohols is reported using an immobilized rhodium catalyst-organic framework (COF) synthesized from alternating ring-opening metathesis polymerization (altROMP) assembly. The catalyst provided TONs as high as 38 000, with catalyst loadings as low as 0.0025 mol% for the isomerizations. Kinetic resolution of starting allylic alcohol 5 was also observed.

---

We report solvent-free isomerizations of allylic alcohols into the corresponding aldehydes and ketones over a rhodium-diphosphine catalyst that is incorporated into a heterogeneous, polymeric catalyst-organic framework (COF). A prominent strategy to minimize the cost and environmental impact of synthesis is to develop atom-economical reactions that occur over reusable catalysts in inexpensive, non-toxic solvents.¹ The catalytic isomerization of allylic alcohols into the corresponding aldehydes or ketones is an ideal candidate for such a transformation because it occurs with 100% atom economy and because it produces useful, versatile products.² For example, the related rhodium-BINAP (BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) catalyzed enantioselective isomerization of diethylgeranylamine (to form the corresponding aldehyde after hydrolysis) is a fundamental step in the industrial preparation of (−)-menthol.³ Extensive mechanistic studies have been carried out on this type of isomerization that generally conclude that these reactions proceed via an intramolecular net 1,3-hydride shift.²

As is the norm for transition-metal catalyzed reactions, isomerizations of allylic alcohols are mostly carried out in organic media.^2,4 The common catalysts for this reaction contain precious metals such as rhodium,^4a–c iridium^4d–g and ruthenium.^4h–q There are examples, however, of catalysts containing non-precious metals such as nickel^5a,b and iron.^5c–e Ruthenium catalyst systems are the most active to date,^4h–q while rhodium- and iridium-containing chiral catalysts are commonly used for enantioselective isomerizations.^4a–g These isomerizations likely proceed with the corresponding enols as intermediates. Indeed, an earlier report shows that rhodium-bis(phosphine) catalysts produce the corresponding enols in high concentrations under rigorously neutral conditions.⁶

Recent studies on low-impact solvents include the use of water,⁷ ionic liquids,^7l and aqueous-biphasic⁸ mixtures with homogeneous catalysts. There are several reports of reusing the catalyst in biphasic solvent systems. The catalyst loadings per run in these systems range from 0.2 to 1.58 mol%.^{7d,e,i,k–m,8d} Most report 4 reuses, highest number is 9.^7d,k The highest total number of turnovers is 2035, obtained after 4 reuses of a ruthenium(IV)-bis(allyl) catalyst.⁷ⁱ To the best of our knowledge, there is only one study reporting the use of a heterogenized catalyst for these isomerizations. A ruthenium-arene-1,3,5-triaza-7-phosphatricyclo [3.3.1.1] decane compound, tethered to Fe₃O₄ nanoparticles, sustained up to 3 reuses without significant loss in activity. The substrate loadings per run were modest, to result in a total turnover number (TON) of 283, after 4 resues.^7m There is only one study of a solvent-free isomerization: the conversion of neat 3-butene-2-ol into 2-butanone with a ruthenium-bis(bipyridine) derivative as catalyst (sub : cat = 1000 : 1, 80 °C, 10 min) reported by Lau et al.⁴ⁱ There are no studies of solvent-free isomerizations of allylic alcohols over a heterogenized catalyst.

As general strategies, homogeneous catalysts are typically immobilized via non-covalent and covalent interactions with a support. Non-covalent immobilization techniques⁹ include electrostatic interactions between charged catalysts and supports, physisorption onto the support, hydrogen bonding, and encapsulation within the support. Covalent immobilization techniques¹⁰ include the formation of metal-support bonds and formation of bonds between a modified ligand and a support. Grafting of modified ligands onto polymeric supports by copolymerization of modified catalyst ligands is often achieved by first incorporating the ligand into the support followed by metalating the incorporated ligand. This approach often results in incomplete metalation of the ligand-polymer support and poor mass transport at the active sites, leading to low catalyst activity and poor reusability. The direct polymerization of metal-containing monomers ensures metalation of the ligand-polymer support,¹¹ but mass transport at the catalytic active sites must still be addressed.

We reported¹² the synthesis of a ruthenium-BINAP-containing COF via an alternating ring-opening metathesis polymerization (altROMP). This ruthenium-based COF was reused for an enantioselective ketone hydrogenation with high TONs per run (> 1000) for 25 runs before loss in activity occurred. More than 35 reuses were carried out without loss in enantioselectivity or detectable leaching of ruthenium. We recently applied the altROMP method¹³ to prepare a rhodium-BINAP-containing COF (1). COF 1 was synthesized via altROMP between the rhodium(I) chloro-bridged dimer [RhCl(2)]₂ (3, 2 = (R)-5,5′-dinorimido-BINAP) and cis-cyclooctene (COE) using the first-generation Grubbs ROMP catalyst, RuCl₂(=CHPh)(PCy₃)₂ (4) (Scheme 1). Briefly, the difference in ring strain and crowding between the norbornene groups in 3 and COE results in an alternating ROMP that assembles the three dimensional, cross-linked COF 1. The COF was deposited as a thin film onto BaSO₄ to provide mechanical stability and to aid mass transport during catalysis. To our knowledge, this framework is the first polymer-based heterogenized catalyst that operates with higher TONs and selectivity than the parent homogeneous catalyst for a particular reaction.¹³ Specifically, we reused 1 (after one activation with AgSbF₆) up to seven times (TONs = 100 per run) for the highly enantioselective intramolecular cycloisomerization of 1,6-enynes. In batch mode, 1 effected the cycloisomerization of CyC≡CCH₂OCH₂CH=CH(CH₂CH₃) with TON = 890 in 2-MeTHF solvent. In comparison, the parent catalyst under typical conditions for the homogeneous reaction (5 mol% (COD)RhCl₂, 10 mol% BINAP, 20 mol% AgSbF₆ in (CH₂Cl)₂) formed a complex mixture of products with TON = 10. We now report the results from our study of the utilization of 1 for high TON, solvent-free isomerizations of allylic alcohols.

Scheme 1 Synthesis of rhodium COF 1.

We initially chose the isomerization of 1-propen-3-ol to evaluate 1. With 0.01 mol% Rh, 0.05 mol% AgSbF₆ at 70 °C in the absence of solvent, a TON of 6150 was obtained after 45 min to produce a mixture containing propanal (55%), 1-propen-3-ol (28%), and the hemiacetal from propanal and 1-propen-3-ol (17%). The hemiacetal resulted from carrying out the isomerization in the absence of solvent. We found, however, that the use of secondary allylic alcohols avoided the formation of hemiacetals. For example, the isomerization of neat 1-buten-3-ol (5) over 1 (0.025 mol% Rh, 0.125 mol% AgBF₄, 70 °C) was complete in 1.25 h to generate 2-butanone as the sole detectable product in ∼4000 TOs.

A factor that will determine the activity of 1 is the extent of activation of the rhodium centers by removal of chloride by the silver salt. Another factor is the coordinating ability of the silver salt anion. Table 1 shows the results from screening a variety of silver salts for the isomerization of neat 5 into 2-butanone

Table 1 Isomerization of 5 by 1/BaSO₄ using different silver salts^a

		TON
Entry	Ag salt	1 h	2 h	24 h	48 h
a All runs were carried out solvent-free at 70 °C, with Sub/Ag/Rh = 40 000/5/1. b These TONs are after 68 h of reaction time.
1	AgSbF6	6000	9200	25 600	28 800
2	AgBF4	6400	9600	31 200	35 200
3	AgOTf	3600	5200	17 200	22 400^b
4	AgClO4	1200	1800	20 800	34 000^b

---

The SbF₆⁻ and the BF₄⁻ silver salts produce catalysts from 1 with higher initial activities than the OTf⁻ and ClO₄⁻. The catalyst with the BF₄⁻ counter ion also effected the isomerization with the highest TON after 48 h (35 200, Table 1, entry 2). The effectiveness of these silver salts to act as chloride extractors from 1 likely relates to their solubility in 5 and to their ability to reach the active sites in 1. We point out that abstraction of chloride from the rhodium centers will convert 1 from a neutral framework cross-linked at rhodium to a more open, charged species. Further investigation is required to determine how the nature of the counter ion would influence the structure and reactivity of such a charged framework. For the purpose of this study, AgBF₄ was used as the chloride abstractor.

Table 2 shows the results we obtained from the isomerizations of a variety of secondary allylic alcohols (Scheme 2). Substrates 5, 6 and 7, which contain shorter terminal alkyl chains than substrates 8 and 9, were the most active (Table 2, entries 1–5). Catalyst loadings as low as 0.0025 mol% (Table 2, entry 2) resulted in a TON of 35 200 for the isomerization of 5. Supports other than BaSO₄ were also shown to be effective (Table 2, entry 3). The use of 1 supported on Ba-(L)-tartrate (0.0025 mol% Rh) resulted in a TON of 38 000, the highest TON reported for the rhodium-catalyzed isomerization of allylic alcohols. However, possible differences in swellability of the support resulted in the higher initial activity of 1/BaSO₄ (TON of 6400 compared to 3600). Although it was necessary to increase the temperature as the terminal alkyl chain in the substrates increased, the catalyst loadings (0.03–0.0025 mol%) were still low relative to the loadings of rhodium catalysts reported in the literature (0.2–5 mol%).^4a–c

Scheme 2 Isomerization of secondary allylic alcohol substrates.

Table 2 Isomerization of secondary allylic alcohol substrates catalysed by 1/BaSO₄^a

Entry	Sub	Sub/Ag/Rh	T/°C	Time (h)	TON (TOF, h^−1)	Yield (%)
a All runs were carried out under solvent-free conditions with AgBF4 as an activator. b 1/Ba-(L)-Tartrate was the catalyst used.
1	5	4000/5/1	70	1.25	3999	99
					(3199)
2	5	40 000/5/1	70	1	6400	16
					(6400)
				2	9600	24
				24	31 200	78
				48	35 200	88
					(733)
3	5 ^b	40 000/5/1	70	1	3600	9
					(3600)
				24	30 000	75
				48	38 000	95
					(792)
4	6	5000/5/1	85	1.5	4999	99
					(3333)
5	7	5000/5/1	85	1	4999	99
					(4999)
6	8	5000/5/1	85	1.5	800	16
					(533)
				17	3150	63
				48	4500	90
					(94)
7	9	3000/5/1	100	22	2550	85
					(116)

---

Table 3 shows the results from a comparison of the isomerization of 5 carried out with the homogeneous catalyst system (0.0025 mol% [RhCl((R)-BINAP)]₂, 0.0125 mol% AgBF₄) under the same solvent-free conditions at 70 °C. It is evident that the immobilized catalyst 1/BaSO₄ is almost twice as active as the homogeneous catalyst in the isomerization of 5. To our knowledge, catalyst 1/BaSO₄ is the only immobilized polymer-based catalyst that is more active than the parent homogeneous catalyst.

Table 3 Comparison between 1/BaSO₄ and [RhCl((R)-BINAP)]₂ catalysed isomerization of 5^a

		TON
Entry	Catalyst	1 h	2 h	24 h
a Both runs were carried out solvent-free at 70 °C, with Sub/Ag/Rh = 40 000/5/1.
1	1/BaSO4	6400	9600	31 200
2	[RhCl((R)-BINAP)]2	2000	3400	17 600

---

To our knowledge, there are three reports^14,15 on the kinetic resolution of allylic alcohols by isomerization (Scheme 3). The study by Noyori^14b reports the highest ee (91%) to date, obtained with the kinetic resolution of 4-hydroxy-2-cyclopentenone by a rhodium-BINAP catalyst. This isomerization required 14 days at 0 °C and proceeded in 27% yield. The most recent study by Crochet and Gimeno^14c reported the use of [RuCl₂(η⁶-arene){(R)-PR-(binaphthoxy)}]-type catalysts in the (S)-enantio-enrichment of 1-phenyl-2-propen-1-ol and related allylic alcohols with ee's ranging from 4–17% (1 mol% cat., 2 mol% KOtBu, in THF solvent at T = 45–75 °C).

Scheme 3 Kinetic resolution of allylic alcohols.

Using 1/BaSO₄ (0.025 mol% Rh, 0.12 mol% AgBF₄) at 30 °C in the absence of solvent, we obtained 38% yield of 2-butanone in the isomerization of substrate 5 after 21 h. The remaining 62% of unreacted 5 had an ee of approximately 13%. Studies on the optimization of reaction conditions and choice of support are underway in our laboratories.

In conclusion, we have presented the altROMP assembly of the BaSO₄ supported COF 1 and its high activity in the solvent-free isomerization of allylic alcohols. Turnover numbers as high as 38 000 were achieved in single-batch reactions, with loadings that are 100–800 times less than is typical for rhodium-based catalysts reported in the literature. We note the highest number of turnovers to date is 1 500 000, reported for the isomerization of 1-octen-3-ol with an achiral ruthenium(IV)-bis(allyl) catalyst.⁷ⁱ

Our immobilized catalyst also provided higher turnover numbers than the parent homogeneous system, a rare occurrence in the field of catalysis. The possible origins of the COF's activity include support (BaSO₄) effects, catalyst-framework interactions, and encapsulation phenomena. Our current research is focused upon optimizing the structure of 1, investigating the origins of its activity, and, in lieu of traditional batch reuses, incorporating 1 into continuous flow reactors.

Acknowledgements

This work was supported by the National Sciences and Engineering Research Council of Canada (NSERC) and the University of Alberta.

References

1. (a) J. A. Linthorst, Found. Chem., 2010, 12, 55–68; (b) I. T. Horváth and P. T. Anastas, Chem. Rev., 2007, 107, 2169–2173; (c) P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, 1998; (d) F. M. Kerton, Alternative Solvents for Green Chemistry, Royal Society of Chemistry, 2009.
2. (a) For recent reviews see: R. C. van der Drift, E. Bouwman and E. Drent, J. Organomet. Chem., 2002, 650, 1–24; (b) R. Uma, C. Crévisy and R. Grée, Chem. Rev., 2003, 103, 27–51; (c) L. Mantilli and C. Mazet, Chem. Lett., 2011, 40, 341–344; (d) V. Cadierno, P. Crochet and J. Gimeno, Synlett, 2008, 1105–1124; (e) G. C. Fu, in Modern Rhodium-Catalyzed Organic Reactions, Wiley-VCH, 2005, 79–91; (f) A. Varela-Álvarez, J. A. Sordo, E. Piedra, N. Nebra, V. Cadierno and J. Gimeno, Chem.–Eur. J., 2011, 17, 10583–10599.
3. (a) K. Tani, T. Yamagata, S. Otsuka, S. Akutagawa, H. Kumobayashi, T. Taketomi, H. Takaya, A. Miyashita and R. Noyori, J. Chem. Soc., Chem. Commun., 1982, 600–601; (b) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, 1994, Chapter 3.
4. (a) K. Tanaka, S. Qiao, M. Tobisu, M. M.-C. Lo and G. C. Fu, J. Am. Chem. Soc., 2000, 122, 9870–9871; (b) K. Tanaka and G. C. Fu, J. Org. Chem., 2001, 66, 8177–8186; (c) M. T. Reetz and H. Guo, Synlett, 2006, 2127–2129; (d) L. Mantilli, D. Gérard, S. Torche, C. Besnard and C. Mazet, Chem.–Eur. J., 2010, 16, 12736–12745; (e) L. Mantilli and C. Mazet, Tetrahedron Lett., 2009, 50, 4141–4144; (f) L. Mantilli and C. Mazet, Chem. Commun., 2010, 46, 445–447; (g) L. Mantilli, D. Gérard, S. Torche, C. Besnard and C. Mazet, Angew. Chem., Int. Ed., 2009, 48, 5143–5147; (h) P. N. Liu, K. D. Ju and C. P. Lau, Adv. Synth. Catal., 2011, 353, 275–280; (i) R. Uma, M. K. Davies, C. Crévisy and R. Grée, Eur. J. Org. Chem., 2001, 3141–3146; (j) B. Martín-Matute, K. Bogár, M. Edin, F. B. Kaynak and J.-E. Bäckvall, Chem.–Eur. J., 2005, 11, 5832–5842; (k) R. C. van der Drift, M. Gagliardo, H. Kooijman, A. L. Spek, E. Bouwman and E. Drent, J. Organomet. Chem., 2005, 690, 1044–1055; (l) M. Ito, S. Kitahara and T. Ikariya, J. Am. Chem. Soc., 2005, 127, 6172–6173; (m) G. Sabitha, S. Nayak, M. Bhikshapathi and J. S. Yadav, Org. Lett., 2011, 13, 382–385; (n) Y. Takai, R. Kitaura, E. Nakatani, T. Onishi and H. Kurosawa, Organometallics, 2005, 24, 4729–4733; (o) P. Crochet, M. A. Fernández-Zúmel, J. Gimeno and M. Scheele, Organometallics, 2006, 25, 4846–4849; (p) M. Batuecas, M. A. Esteruelas, C. García-Yebra and E. Oñate, Organometallics, 2010, 29, 2166–2175; (q) A. Bouziane, B. Carboni, C. Bruneau, F. Carreaux and J.-L. Renaud, Tetrahedron, 2008, 64, 11745–11750.
5. (a) H. Bricout, E. Monflier, J.-F. Carpentier and A. Mortreux, Eur. J. Inorg. Chem., 1998, 1739–1744; (b) D. Cuperly, J. Petrignet, C. Crévisy and R. Grée, Chem.–Eur. J., 2006, 12, 3261–3274; (c) V. Branchadell, C. Crévisy and R. Grée, Chem.–Eur. J., 2003, 9, 2062–2067; (d) H. Cherkaoui, M. Soufiaoui and R. Grée, Tetrahedron, 2001, 57, 2379–2383; (e) C. Crévisy, M. Wietrich, V. Le Boulaire, R. Uma and R. Grée, Tetrahedron Lett., 2001, 42, 395–398.
6. J. A. Wiles, C. E. Lee, R. McDonald and S. H. Bergens, Organometallics, 1996, 15, 3782–3784.
7. (a) N. Ahlsten, H. Lundberg and B. Martín-Matute, Green Chem., 2010, 12, 1628–1633; (b) D. A. Knight and T. L. Schull, Synth. Commun., 2003, 33, 827–831; (c) D. H. Leung, R. G. Bergman and K. N. Raymond, J. Am. Chem. Soc., 2007, 129, 2746–2747; (d) P. Crochet, J. Díez, M. A. Fernández-Zúmel and J. Gimeno, Adv. Synth. Catal., 2006, 348, 93–100; (e) A. E. Díaz-Álvarez, P. Crochet, M. Zablocka, C. Dunhayon, V. Cadierno, J. Gimeno and J. P. Majoral, Adv. Synth. Catal., 2006, 348, 1671–1679; (f) V. Cadierno, S. E. García-Garrido and J. Gimeno, Chem. Commun., 2004, 232–233; (g) B. Lastra-Barriera, J. Díez and P. Crochet, Green Chem., 2009, 11, 1681–1686; (h) T. Campos-Malpartida, M. Fekete, F. Joó, Á Kathó, A. Romerosa, M. Saoud and W. Wojtków, J. Organomet. Chem., 2006, 693, 468–474; (i) V. Cadierno, S. E. García-Garrido, J. Gimeno, A. Varela-Álvarez and J. A. Sordo, J. Am. Chem. Soc., 2006, 128, 1360–1370; (j) B. González, P. Lorenzo-Luis, M. Serrano-Ruiz, É. Papp, M. Fekete, K. Csépke, K. Ősz, Á. Kathó, F. Joó and A. Romerosa, J. Mol. Catal. A: Chem., 2010, 326, 15–20; (k) A. Azua, S. Sanz and E. Peris, Organometallics, 2010, 29, 3661–3664; (l) J. García-Álvarez, J. Gimeno and F. J. Suárez, Organometallics, 2011, 30, 2893–2896; (m) S. E. García-Garrido, J. Francos, V. Cadierno, J.-M. Basset and V. Polshettiwar, ChemSusChem, 2011, 4, 104–111; (n) A. Pontes da Costa, J. A. Mata, B. Royo and E. Peris, Organometallics, 2010, 29, 1832–1838.
8. (a) C. Bianchini, A. Meli and W. Oberhauser, New J. Chem., 2001, 25, 11–12; (b) H. Bricout, E. Monflier, J.-F. Carpentier and A. Mortreaux, Eur. J. Inorg. Chem., 1998, 1739–1744; (c) M. Fekete and F. Joó, Catal. Commun., 2006, 7, 783–786; (d) V. Cadierno, P. Crochet, S. E. García-Garrido and J. Gimeno, Dalton Trans., 2004, 3635–3641.
9. (a) For recent reviews see: J. M. Fraile, J. I. García and J. A. Mayoral, Chem. Rev., 2009, 109, 360–417; (b) M. Heitbaum, F. Glorius and I. Escher, Angew. Chem., Int. Ed., 2006, 45, 4732–4762; (c) P. McMorn and G. J. Hutchings, Chem. Soc. Rev., 2004, 33, 108–122; (d) X. S. Zhao, X. Y. Bao, W. Guo and F. Y. Lee, Mater. Today, 2006, 9(3), 32–39.
10. (a) For recent reviews see: B. M. L. Dioos, I. F. J. Vankelecom and P. A. Jacobs, Adv. Synth. Catal., 2006, 348, 1413–1446; (b) N. E. Leadbeater and M. Marco, Chem. Rev., 2002, 102, 3217–3274; (c) Q.-H. Fan, Y.-M. Li and A. S. C. Chan, Chem. Rev., 2002, 102, 3385–3466; (d) Z. Wang, G. Chen and K. Ding, Chem. Rev., 2009, 109, 322–359; (e) K. Ding, Z. Wang, X. Wang, Y. Liang and X. Wang, Chem.–Eur. J., 2006, 12, 5188–5197; (f) For MOFs see: Y. Liu, W. Xuan and Y. Cui, Adv. Mater., 2010, 22, 4112–4135; (g) A. Corma, H. García and F. X. Llabrés i Xamena, Chem. Rev., 2010, 110, 4606–4655; (h) L. Ma, C. Abney and W. B. Lin, Chem. Soc. Rev., 2009, 38, 1248–1256.
11. P. Mastrorilli and C. F. Nobile, Coord. Chem. Rev., 2004, 248, 377–395.
12. (a) C. K. Ralph, O. M. Akotsi and S. H. Bergens, Organometallics, 2004, 23, 1484–1486; (b) C. K. Ralph and S. H. Bergens, Organometallics, 2007, 26, 1571–1574.
13. E. G. Corkum, M. J. Hass, A. D. Sullivan and S. H. Bergens, Org. Lett., 2011, 13, 3522–3525.
14. (a) K. Ohkubo, T. Ohgushi, T. Kusaga and K. Yoshinaga, Inorg. Nucl. Chem. Lett., 1977, 13, 631–636; (b) M. Kitamura, K. Manabe and R. Noyori, Tetrahedron Lett., 1987, 28, 4719–4720; (c) M. A. Fernández-Zúmel, B. Lastra-Barriera, M. Scheele, J. Díez, P. Crochet and J. Gimeno, Dalton Trans., 2010, 39, 7780–7785.
15. Bergens et al. reported the kinetic resolution of 3-buten-2-ol, however the enol, rather than the ketone, product was obtained. For more information see ref. 6.

---

Footnote

† Electronic Supplementary Information (ESI) available: Text giving experimental procedures for catalyst-organic framework preparation and use and kinetic resolution determination. See DOI: 10.1039/c2ra20197f/

---