8/3/2019 Michael C. Willis and Selma Sapmaz- Intermolecular hydroacylation of acrylate esters: a new route to 1,4-dicarbonyls

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Communication

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CHEMCOM

M

Intermolecular hydroacylation of acrylate esters: a new route to

1,4-dicarbonyls

Michael C. Willis* and Selma Sapmaz

Department of Chemistry, University of Bath, Bath, UK BA2 7AY. E-mail: m.c.willis@bath.ac.uk;

Fax: (+44) (0)1225 826231; Tel: (+44) (0)1225 826568

Received (in Cambridge, UK) 31st August 2001, Accepted 15th October 2001First published as an Advance Article on the web 22nd November 2001

1,4-Dicarbonyl compounds can be prepared using a Rh(I)mediated hydroacylation reaction between(2-aminopicolyl)imines and acrylate esters followed by acidhydrolysis.

The transition metal catalysed hydroacylation reaction in whichan aldehyde and an alkene are combined to generate a ketone isa relatively unexplored process. The main limitation of thisreaction is the instability of the proposed acyl-metal inter-

mediates and the resulting competitive decarbonylation path-way.1 Intramolecular variants of the process utilising pent-4-en-1-als as substrates, leading to cyclopentanones as products, havebeen extensively studied,2 however reports leading to largerring sizes3 or intermolecular examples are scarce.4 Recently theJun group have reported the use of a reaction system employingWilkinsons complex and 2-aminopicoline as catalysts thatallows intermolecular hydroacylation to proceed.5 The successof the Jun system is attributed to the intermediacy of apicolylimine capable of forming a chelate stabilised acylrho-dium species.6 The majority of hydroacylation reactionsreported to date utilise unfunctionalised alkenes as substratesthus generating simple ketones as products. We speculated thatthe use of alkenes substituted directly with either an ester orketone group would provide direct access to the syntheticallychallenging 1,4-dicarbonyl array (Scheme 1). These 1,4-di-functionalised motifs are synthetically useful intermediates forthe preparation of substituted furans,7 butyrolactones8 andsuccinate derivatives.9 Such 1,4-dicarbonyl systems are notstraightforward to prepare and the approach presented here canbe considered as the equivalent of an acyl-anion addition to anenoate.10 The related hydroformylation reaction has beenreported although in these cases, by definition, only a singlecarbon unit corresponding to the CO molecule is introduced.11

Using variously substituted and functionalised aldehydes in thecorresponding hydroacylation reaction would allow the addi-tion of functionalised carbon chains.12 In this communicationwe report our progress towards this goal.

To assess the feasibility of the process we elected to study thereactions of imine 1 as an aldehyde equivalent and thus limitdecarbonylation. The reaction of1 with methyl acrylate under avariety of reaction conditions is summarised in Table 1.Reactions were conducted in a sealed tube using Wilkinsonscomplex as the catalyst. Upon completion the reaction mixtureswere treated directly with 1.0 M HCl to liberate the required1,4-dicarbonyl adducts. Optimal conditions involved heating aTHF solution of the substrates at 135 C for 6 hours with 10mol% catalyst (entry 1). Under these conditions the desired

product was isolated in 73% yield as a single regioisomer.Lowering the catalyst loading or reaction temperature ordecreasing the reaction time resulted in less efficient processes(entries 24). The reaction also proceeds if toluene is employedas solvent although a more complex reaction mixture isproduced resulting in lower yields (entry 5). Chlorobenzene wasalso evaluated but resulted in only low conversion to product.The use of 1,4-dioxane allowed a reasonable yield of the desiredproduct to be isolated however solubilty problems were

encountered that were not observed with THF.In order to probe the generality of the process a range of

substituted enoates were evaluated in the reaction with imine 1(Table 2). Variation in the ester group is tolerated well, with Meand tBu esters both delivering the expected adducts in goodyields (entries 1 and 2).13 Entry 3 demonstrates the tolerancetowards amides with N,N-dimethylacrylamide generating thecorresponding product in 74% yield. The introduction ofsubstituents to the b-position of the alkene significantly reducesthe reaction efficiency with methyl crotonate and cinnamatedelivering the desired adducts in 24% and 10% yield re-spectively (entries 4 and 5). Substitution at the a-position has asimilar effect on the reaction efficiency with methyl methacry-late yielding 16% of the requisite product (entry 6). A b-substituent could be successfully introduced if it was suffi-ciently activating, thus the use ofN-methyl maleimide as thealkene component generated the desired hydroacylation productin 81% yield (entry 7).

The generality with respect to the imine component was nextexplored; we were particularly interested in assessing theinfluence of electron withdrawing and donating substituents onthe aryl ring. A selection of 2-amino-3-methylpyridyliminesbearing a range of substituents were readily prepared andevaluated in the reaction with methyl acrylate (Table 3).Electron withdrawing groups such as -NO2 and -CN had abeneficial effect on the rate of the reaction with good yields ofthe desired products being obtained in only 20 and 80 minrespectively (entries 2 and 3). Electron donating substituents

Electronic supplementary information (ESI) available: experimentaldetails. See http://www.rsc.org/suppdata/cc/b1/b107852f/

Scheme 1

Table 1 Reaction of imine 1 with methyl acrylatea

Entry Temp./ C Solvent Time/h Yield (%)

1 135 THF 6 732b 135 THF 6 473 70 THF 7 484 135 THF 4 595 135 PhMe 6 56

a Conditions: imine 1 (1.0 eq.), methyl acrylate (2.0 eq), sealed tube,RhCl(PPh3)3 (10 mol%) followed by HCl (1.0 M). b RhCl(PPh3)3 (5mol%).

This journal is The Royal Society of Chemistry 2001

2558 Chem. Commun., 2001, 25582559 DOI: 10.1039/b107852f

8/3/2019 Michael C. Willis and Selma Sapmaz- Intermolecular hydroacylation of acrylate esters: a new route to 1,4-dicarbonyls

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had a smaller influence on the rate of reaction; a -OMesubstituent had minimal effect compared to the parent phenylsystem with an 83% yield being achieved after 6 h (entry 4).

para-Methyl and -bromo groups are also well tolerateddelivering the corresponding 1,4-dicarbonyls in 98% and 85%yield respectively (entries 5 and 6). Exchange of a phenyl for themore electron rich naphthyl derived imine again showed littledifference with the naphthyl derived adduct being obtained in86% yield after 6 h reaction (entry 7).

The reason for the rate accelerations observed with the nitro-and cyano-substituted imines is unclear although destabilisationof the chelated intermediate is a possibility. Given these rateaccelerations we were interested to see if these more reactiveimines would allow a- and b-substituted acrylate esters to beemployed as substrates. Unfortunately, although a rate accelera-tion was observed little difference in yield was obtained, withthe nitro-substituted imine delivering products from reactionwith methyl crotonate and methyl methacrylate in only 22% and14% yield respectively.

The use of diimine 2, prepared in good yield from benzene-1,4-dicarboxaldehyde, offers a potential starting point for twodirectional synthesis14 and allowed a double hydroacylation to

be attempted. Pleasingly, the required tetracarbonyl product 3was isolated in 76% yield after 6 hours reaction.15

In conclusion, we have demonstrated the general viability ofthe intermolecular hydroacylation of acrylate esters as a newregioselective route to 1,4-dicarbonyl systems. The iminecomponent of the reaction can tolerate a range of substituentsincluding electron donating and electron withdrawing groups.The enoate component can contain a variety of ester groups aswell as amide functionalities with little effect on yield, however,introduction of simple a- or -substituents reduces the efficiencyof the reactions. Efforts to expand the substrate tolerance, toidentify more efficient catalyst systems and to develop a processthat can utilise aldehydes directly are underway in our

laboratory and will be reported in due course.The EPSRC are thanked for financial support of this project.

We also thank the EPSRC Mass Spectrometry service at theUniversity of Wales, Swansea, for analyses and JohnsonMatthey PLC for the loan of rhodium salts.

Notes and references

1 J. M. OConnor and M. Junning,J. Org. Chem., 1992, 57, 5075.2 For leading refs, see: (a) R. W. Barnhart, D. A. McMorran and B.

Bosnich,Inorg. Chim. Acta, 1997, 263, 1; (b) B. Bosnich,Acc. Chem.Res., 1998, 31, 667; (c) M. Fujio, M. Tanaka, X.-M. Wu, K. Funakoshi,K. Sakai and H. Suemune, Chem. Lett., 1998, 881.

3 For examples, see: A. D. Aloise, M. E. Layton and M. D. Shair,J. Am.Chem. Soc., 2000, 122, 12610; K. P. Gable and G. A. Benz, TetrahedronLett., 1991, 32, 3473.

4 For leading refs, see: H. Lee and C.-H. Jun,Bull. Korean Chem. Soc.,1995, 16, 66; C. P. Lenges, P. S. White and M. Brookhart,J. Am. Chem.Soc., 1998, 120, 6965; T. Kondo, M. Akazome, Y. Tsuji and Y.Watanabe, J. Org. Chem., 1990, 55, 1286; T. Kondo, N. Hiraishi, Y.Morisaki, K. Wada, Y. Watanabe and T.-A. Mitsudo, Organometallics,1998, 17, 2131.

5 C.-H. Jun, D.-Y. Lee, H. Lee and J.-B. Hong,Angew. Chem., Int. Ed.,2000, 39, 3070.

6 J. W. Suggs,J. Am. Chem. Soc., 1979, 101, 489.7 W. Friedrichsen, Furans and their benzo derivatives: synthesis, in

Compr. Heterocycl. Chem. II, ed. C. W. Bird, Elsevier, Oxford, 1996.8 E.-I. Negishi and M. Kotora, Tetrahedron, 1997, 53, 6707.9 R. E. Babine and S. L. Bender, Chem. Rev., 1997, 97, 1359.

10 D. Seebach,Angew. Chem., 1979, 91, 259; Umpoled Synthons. A Surveyof Sources and Uses in Synthesis, ed. T. A. Hase, Wiley, New York,1987.

11 For examples, see: G. Fremy, E. Monflier, J.-F. Carpentier, Y. Castanetand A. Mortreux,Angew. Chem., Int. Ed. Engl., 1995, 34, 1474; C. W.Lee and H. Alper,J. Org. Chem., 1995, 60, 499; Y. Hu, W. Chen, A. M.B. Osuna, J. Xiao, A. M. Stuart and E. G. Hope, Chem. Commun., 2001,725.

12 For an example of an intramolecular hydroacylation of an acrylate estersee ref. 2(a).

13 All new compounds have been characterised, see ESI for details.14 For a review, see: S. R. Magnuson, Tetrahedron, 1995, 51, 2167.15 The preparation of3 serves as a general procedure: a solution of imine

2 (282 mg, 1.79 mmol) in THF (1 mL) was added to a solution ofRhCl(PPh3)3 (167 mg, 10 mol %) in THF (1 mL) at room temperatureand stirred for 1 h. Methyl acrylate (480 mL, 5.37 mmol) in THF (2 mL)was added and the reaction vessel flushed with argon. The reaction tubewas sealed and then heated at 135 C for 6 h. The reaction was cooledto room temperature, diluted with EtOAc (20 mL), poured into aqueousHCl (1 M, 20 mL) and extracted with EtOAc (3 3 20 mL). The organic

portions were washed with brine (20 mL), dried (MgSO4) andevaporated in vacuo. The residue was purified by flash chromatography(SiO2, 25% EtOAcpetrol) to give 3 (212 mg, 76%) as pale yellowplates.

Table 2 Reaction between 1 and various alkenes using RhCl(PPh3)3a

Entry Alkene Product Time/hYield(%)

1 X = OMe R1 = R2 = H 6 732 X = OtBu R1 = R2 = H 6 713 X = NMe2 R1 = R2 = H 6 74

4R1 = Me, R2 = HX = OMe 18 24

5R1 = Ph, R2 = HX = OMe 12 10

6

R1 = H, R2 = Me

X = OMe 12 16

7b 6 81

a Conditions: imine 1 (1.0 eq.), alkene (2.0 eq), THF, 135 C, sealed tube,RhCl(PPh3)3 (10 mol%) followed by HCl (1.0 M). b Product isolated asenamine. pic = 3-picolin-2-yl.

Table 3 Variation in imine substituenta

Entry R Time/h Yield (%)

1 X = H 6 h 732 X = NO2 20 min 803 X = CN 80 min 804 X = OMe 6 h 835 X = Me 6 h 986 X = Br 6 h 857 6 h 86

a Conditions: imine (1.0 eq.), methyl acrylate (2.0 eq), THF, 135 C, sealedtube, RhCl(PPh3)3 (10 mol%) followed by HCl (1.0 M).

Chem. Commun., 2001, 25582559 2559