Directing the regioselectivity of rhodium(I) catalysed cyclisation of 2-alkynyl benzoic acids

Polyhedron 61 (2013) 248–252

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Directing the regioselectivity of rhodium(I) catalysed cyclisation of 2-alkynyl benzoic acids Bradley Y.-W. Man, Astrid Knuhtsen, Michael J. Page, Barbara A. Messerle ⇑ School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia

a r t i c l e

i n f o

Article history: Received 16 May 2013 Accepted 9 June 2013 Available online 20 June 2013 Keywords: Rhodium Hydroalkoxylation Catalysis Tris(imidazolyl)methanol

a b s t r a c t Rhodium(I) dicarbonyl complexes 1–4 containing chelating N-donor ligands bis(pyrazolyl)methane (bpm), bis(imidazolyl)methane (bim), tris(pyrazolyl)toluidine (tpt) or tris(imidazolyl)methanol (tim) were investigated as catalysts for the hydroalkoxylation of alkynyl benzoic acids (5a–g). The regioselectivity of the reaction was shown to be highly dependent on the nature of the terminal alkyne substituent (R) of the alkynol substrate. It was also determined that the presence of a third uncoordinated N-donor group in complexes 3 and 4 suppressed the catalytic efficiency of these complexes, and that the selectivity of the reaction for forming either endocyclic (6) or exocyclic (7) hydroalkoxylation products was influenced by the pendant hydroxyl group present in complex 4. We used 13C NMR spectroscopy to quantify the polarity of the alkynyl benzoic acid C„C bond and our efforts to correlate this measure of bond polarity to the observed regioselectivity of the reaction are discussed. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction Phthalide [1] and isocoumarin [2] compounds that contain a lactone functional group fused with a phenyl ring (Scheme 1) are an important class of natural products prevalent in a wide range of biologically active pharmaceutical, antifungal and pesticidal agents. The cyclisation of 2-alkynyl benzoic acids represents an important and atom efficient approach to the synthesis of both groups of compounds depending on the regioselectivity of the reaction. A number of different catalysts are known to facilitate this transformation, including late transition metal complexes of Pd [3], Cu [4], Ag [5], Au [6] and Ir [7], weak bases such as DBU, Et3N and KOAc, and strong acids such as H2SO4 and CF3SO3H [8]. Unfortunately, for a majority of these systems a mixture of regioisomers is obtained decreasing the overall yield of desired product and leading to expensive separation procedures. Therefore the development of catalysts that can selectively yield one regioisomer in preference to the other is a highly sought after goal. We have previously demonstrated that rhodium(I) complexes containing bidentate nitrogen donor ligands are highly effective catalysts for the intramolecular cyclisation of aliphatic alkynoic acids [9] and other related C–O bond forming reactions [10]. Some of the most active catalysts for these transformations are dicarbonyl Rh(I) complexes 1 and 2 containing the ligands bis(pyrazolyl)methane (bpm) and bis(imidazolyl)methane (bim), respectively. More recently we reported the analogous rhodium(I) complexes 3 ⇑ Corresponding author. Tel.: +61 293854653. E-mail address: [email protected] (B.A. Messerle). 0277-5387/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.poly.2013.06.010

and 4 containing the ligands tris(pyrazolyl)toluidine (tpt) and tris(imidazolyl)methanol (tim), respectively, where the ligand coordinates in a bidentate j2-fashion through only two of the N-donor groups [11]. The presence of a pendant coordinating group, as is found in 3 and 4, has been shown in many examples to strongly influence the catalytic properties of a complex. For example dicarbonyl rhodium(I) complexes containing j2-tris(pyrazolyl) donor ligands are far more active catalysts for the hydroformylation of alkenes compared to related complexes containing bis(pyrazolyl) chelates [12]. Cavell and co-workers also found that donor functionalised bis(imidazolyl) chelates gave palladium(II) Heck reaction catalysts [13] and chromium(III) ethylene oligomerization catalysts [14] of various activities depending on the nature of the pendant coordinating group. The pendant hydroxyl group in complex 4 also has the potential to participate in metal binding [15] or intermolecular hydrogen bonding [16] interactions which may similarly influence the reactivity of this complex. We report here the activity of complexes 1–4 as catalysts for the intramolecular cyclisation of 2-alkynyl benzoic acids to yield phthalide and isocoumarin products. We were particularly interested in whether the presence of the pendant N-donor or hydroxyl groups in complexes 3 and 4 would have an impact on the efficiency and regioselectivity of this reaction. The identity of the terminal alkyne substituent (R) also has a significant impact on the reaction selectivity [3c,4,6]. To understand this influence we have used 13C NMR spectroscopy to determine the C„C bond polarity for a variety of alkyne substrates. Our efforts to correlate this measure of bond polarity with the observed regioselectivity of the reaction are also reported.

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X

N

N

N

N

X

H2N

X N

Rh OC

N

CO 1

X

N

N

N

N N

N

Rh

OC

N

N Rh

OC

N

N

N

CO

OC

3

CO

N

HO

N

Rh

N CO

4

X = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BAr F )

2

phthalide as the sole products. Fig. 1 shows an NMR stack plot following the cyclisation of 5a catalysed by the Rh(I) complex with a bidentate ligand, 2. The reaction was complete in less than 1.3 h for all substrates and catalysts (Table 1), with the exception of the cyclisation of the phenyl substituted alkyne (5b) catalysed by 4 which took 6 h. Such reaction efficiency is comparable to the most active catalysts reported for this transformation [3–7]. Several clear trends can be seen by comparing the reactivity of catalysts 1–4 for the cyclisation of substrates 5a–c (Table 1). Firstly, for all catalysts the regioselectivity of the reaction is strongly dependent on the alkyne substituent R. For terminal alkynes the exocyclic phthalide product 7a is favoured (entries 1 and 2), however for phenyl and pentyl substituted alkynes the

2. Results and discussion 2.1. Cyclisation of terminal, aryl and alkyl substituted alkynyl benzoic acids (5a–c) We investigated the catalysed cyclisation of 2-(ethynyl)benzoic acid (5a, R = H), 2-(phenylethynyl)benzoic acid (5b, R = Ph) and 2(1-heptynyl)benzoic acid (5c, R = C5H11) to form the corresponding isocoumarin (6a–c) and phthalide (7a–c) products using complexes 1–4 as catalysts (Table 1). The reactions were carried out using 1 mol% of catalyst at 60 °C in C6D6 and the reaction progress was monitored by 1H NMR spectroscopy. The reaction was observed to proceed very cleanly to yield the isocoumarin and

R

R cat.

O

R

cat. OH

O

O

O

O isocoumarin

phthalide

Scheme 1. Isocoumarin and phthalide regioisomers formed upon the catalysed cyclisation of 2-alkynyl benzoic acids.

Table 1 Reaction time and product ratio for the hydroalkoxylation of 5a–c using 1 mol% of catalyst 1–4 at 60 °C in C6D6.

R

R R

1 mol% cat. OH

C6D6, 60 oC

O R= H (5a) Ph(5b) C5H11 (5c)

a

O

O

+

O

O R= H (6a) Ph( 6b) C5H11 ( 6c)

R= H ( 7a) Ph(7b) C5H11 (7c)

Entry

Catalyst

R

Reaction time/ha

Product ratio (6:7)

1 2 3 4 5 6 7 8

2 4 2 4 2 4 1 3

H H Ph Ph C5H11 C5H11 Ph Ph

0.42 0.67 0.20 6.00 0.27 1.28 0.15 1.25

0.31:1 0.01:1 1:0.11 1:0.50 1:0.00 1:0.00 1:0.04 1:0.05

Time at >99% conversion.

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Fig. 1. 1H NMR spectra for the cyclisation of 5a catalysed by 2 in C6D6 showing clean formation of the isocoumarin (6a) and phthalide (7a) reaction products.

O

O

O

O δ

δ

O

R

R

TS-endoa [Rh]

O

6

or O

O

R [Rh]

O

A

δ

TS-exo

O δ R

[Rh]

R 7

Scheme 2. Proposed mechanism for the Rh(I) catalysed hydroalkoxylation of 2-alkynyl benzoic acids.

Table 2 C NMR chemical shifts (d) of the methyl esters 8a–c.

13

R

C1 .

O

R

C2

OMe R= H (8a) Ph(8b) C5H11 (8c)

H Ph C5H11

13

C chemical shift (d)/ppm

C1

C2

82.4 88.3 79.2

82.1 94.4 96.1

Dd (C1–C2) 0.3 6.1 16.9

endocyclic isocoumarin products 6b and 6c are favoured (entries 3–8). Comparing the results for catalyst 2 containing the bidentate bis(imidazolyl)methane ligand, and catalyst 4 containing the tridentate tris(imidazolyl)methanol ligand, we see a large difference in the proportion of minor product formed. For example, with catalyst 2 when R = H both exo- and endo-cyclic products are formed in significant yield, in a ratio of approx. 1:3 (6:7, entry 1), and for R = Ph the endo-cyclic product is clearly favoured, at a ratio of 6:7  10:1 (entry 3). However when catalyst 4 is used cyclisation of the terminal alkyne (R = H) yields almost exclusively the exocyclic product 7a (6:7 = 0.01:1, entry 2), and for R = Ph a much

higher proportion of the exo-cyclic product 7b is also obtained (6:7 = 1:0.5, entry 4). These results suggest that the structure of the tris(imidazolyl)methanol (tim) ligand in catalyst 4 has a directing influence on the reaction which favours formation of the exocyclic products. This trend does not extend to substrate 5c (R = C5H11) where both catalysts yield exclusively the endocyclic product 6c. To confirm that the difference in product distribution was not a result of interconversion of 6–7 over the longer time frames required with catalyst 4 we monitored the reactions for several hours after completion. No change in the product ratios was observed. In contrast to this, catalyst 1 containing the bidentate bis(pyrazolyl)methane ligand and catalyst 3 containing the tridentate tris(pyrazolyl)toluidine ligand both give similar product ratios for the cyclisation of 5b (R = Ph, entries 7 and 8). These results are also similar to that obtained with catalyst 2 (entry 3) containing the bidentate bis(imidazolyl)methane ligand and all three species can be assumed to react in a similar manner. Catalyst 4 is unique in that the ligand contains a protic OH group located proximal to the reactive metal centre. For catalyst 4 the directing influence of the tris(imidazolyl)methanol (tim) ligand is most likely due to its pendant hydroxyl group, which has the potential to form hydro-

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Table 3 Correlation of the Hammet constant (r) for para-substituents (X), alkyne 13C NMR chemical shifts (d) for 8d–g and the reaction time and product ratios for the cyclisation of 5d–g using catalyst 2.

X

X

X

X C1

C2 1 mol% 2 OH

OMe

O X= OMe (5d) Me (5e) Cl (5f) C(O)Me ( 5g)

O X= OMe (8d) Me (8e) Cl (8f) C(O)Me ( 8g) Entry

X

13

r

C 1 2 3 4 5 a b

OMe Me H Cl C(O)Me

0.268 0.170 0 0.227 0.500

O

C6D6, 60 oC

86.9 87.7 88.3 89.3 91.5

O

O X= OMe (6d) Me (6e) Cl (6f) C(O)Me (6g)

C chemical shift (d)/ppm

1

2

C

94.5 94.7 94.4 92.9 93.3

1

O

+

X= OMe (7d) Me (7e) Cl (7f) C(O)Me (7g) Reaction time/ha

Product ratio (6:7)

3.67b 5.68b 0.20 2.13 0.25

1:0.12 1:0.00 1:0.11 1:0.09 1:0.18

2

Dd (C –C ) 7.6 7.0 6.1 3.6 1.8

Time at >99% conversion. Maximum conversion of 90% achieved.

gen-bonding interactions with the carboxylic acid moiety of the substrate. Further work is ongoing to understand this effect. At all times the reactions catalysed by complexes 3 and 4 containing tridentate ligands were found to be slower than the reactions catalysed by the bidentate ligand complexes 1 and 2. This is perhaps unsurprising as the third N-donor in 3 and 4 is likely to inhibit coordination of the substrate via steric shielding of the metal centre and/or competition for binding to vacant metal coordination sites.

the nucleophilic oxygen leading to formation of the endocyclic isocoumarin product 6c, which is in fact the exclusive product observed experimentally (Table 1, entry 5). This preference is reduced for 5b (Dd(8b) = 6.1 ppm), with formation of a small proportion of the exocyclic product 7b (ca. 10%, Table 1, entry 3). Finally, for the terminal alkyne 5a (R = H) the bond polarity is reversed (Dd(8a) = 0.25 ppm) and the reaction now favours formation of the exocyclic product 7a, although as the magnitude of the C„C polarisation is less pronounced a greater proportion of the minor regioisomer 6a (ca. 25%) is also formed (Table 1, entry 1).

2.2. Mechanistic considerations The first step in the transition metal catalysed cyclisation of alkynyl benzoic acids is the coordination of the alkyne moiety to an electrophilic metal centre (A), which activates the alkyne towards nucleophilic attack by the carboxylate group (Scheme 2) [6,10a,17]. The regioselectivity of the reaction then depends on which transition state (TS-exo or TS-endo, Scheme 2) is most stable, which is strongly influenced by the initial polarity of the C„C bond. We were interested in understanding how the nature of the alkyne substituent R affects the C„C bond polarity and thereby which regioisomer is preferred from this reaction. A well-known measure of the relative electron density at a particular carbon atom is the 13C NMR chemical shift [18], where for an alkyne bonded carbon pair the higher the observed chemical shift, the less shielded the atom nucleus and the less electron density about the carbon atom. In order to minimise the impact of hydrogen bonding on determining the electronic structure of the alkyne we acquired the 13C NMR spectra of the methyl esters 8a–c rather than their parent acids. The 13C NMR chemical shift (d) of the alkyne carbons C1 and C2 of 8a–c are reported in Table 2, along with the difference in chemical shift (Dd) which gives an indication of the bond polarisation. A good correlation between the sign and magnitude of Dd and the observed regioselectivity of the cyclisation reaction catalysed by 2 was observed. For example, the polarisation is greatest for 8c (R = C5H11, Dd = 16.9 ppm) with the d+ charge residing on the C2 carbon which has the higher chemical shift. For substrate 5c (R = C5H11) the large d+ charge on C2 would favour its attack by

2.3. Tuning of C„C bond polarity We were interested in establishing whether we could fine tune the regioselectivity of the cyclisation reaction by varying the electronic properties of the R substituent of the substrate and hence the polarity of the C„C bond. We therefore investigated the hydroalkoxylation of the 2-(phenylethynyl)benzoic acids 5d–g, containing a series of electron donating or electron withdrawing substituents (X) in the para-position of the terminal phenyl ring (Table 3). These results are associated with the alkyne 13C NMR chemical shifts of the corresponding methyl esters 8d–g and a Hammet constant (r) for the para-substituent [19]. Satisfyingly, we can see that as the electron withdrawing nature of the phenyl substituent increases (i.e. increasing r) the polarity of the alkyne bond decreases (smaller Dd). We would therefore expect a corresponding increase in the proportion of exocyclic product 7d–g formed from the cyclisation of the alkynoic acids 5d–g. Unfortunately we see no correlation between alkyne bond polarity and product ratio (6:7). This suggests that the relatively small change in bond polarity observed here for the group of substrates 5d–g (which is much less than that seen for the group of substrates 5a–c) is insufficient to direct the regioselectivity of the reaction. Surprisingly, variation of the para-substituent (X) had a large impact on the reaction rate. Particularly slow rates were observed for the cyclisation of 5d and 5e containing the electron donating OMe and Me substituents, respectively, however a clear correlation between alkyne bond polarity and reaction rate was not observed.

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3. Conclusions

Appendix A. Supplementary data

We have shown that the rhodium(I) compounds 1–4 are effective catalysts for the hydroalkoxylation of a variety of alkynyl benzoic acids. The presence of a pendant N-donor group in complexes 3 and 4 led to a decrease in catalyst activity relative to complexes 1 and 2. Interestingly, the pendant hydroxyl group in complex 4 appeared to have a significant impact on the regioselectivity of the catalyst leading to an increased preference for forming the exocyclic phthalide products (7a,b). Overall, the regioselectivity of these reactions was dominated by the nature of the terminal alkyne substituent (R). The use of 13C NMR spectroscopy provided an accurate description of alkyne bond polarity, however, no correlation was observed between this measurement and the observed regioselectivity or rate of the reaction.

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.poly.2013.06.010.

4. Experimental We have previously reported the preparation of the rhodium complexes 1–4. The alkynoic acids (5a–g) and esters (8a–g) were prepared following modified literature procedures [6,20]. The experimental method and spectroscopic data for compounds 5c, 5g and 8g that have not been reported previously are included in the Supporting information. Characterisation of the cyclised isocoumarin (6a–f) [6,21] and phthalide (7a–f) [6,22] products were identified by comparison of their 1H NMR spectroscopic data with reported literature values where available. The 1H and 13C NMR spectral assignments for the new compounds 6g and 7g are included in the Supporting information. 4.1. Generalised procedure for metal catalysed hydroalkoxylation reactions Catalysed hydroalkoxylation reactions were conducted on a small scale in NMR tubes fitted with a concentric Teflon valve. Deuterated benzene was dried over Na/benzophenone, distilled into the NMR tube containing the catalyst precursor (complexes 1–4, 1 mol%) and substrate (ca. 25 mg), and the sample heated to 60 °C inside the NMR spectrometer. The temperature in the NMR spectrometer was calibrated using neat ethylene glycol and a K-type thermocouple. The progress of the reaction was monitored by 1H NMR spectroscopy by comparing the integration of starting material and product proton resonances. The identity of the product was confirmed by comparison with the literature and/or characterisation using standard 2D NMR spectroscopic techniques. Acknowledgements We gratefully acknowledge financial support from the University of New South Wales, the Australian Research Council, and the Australian government for an Australian Postgraduate Award (B.Y.-W.M.).

References [1] (a) T. Tsuchida, M. Kobayashi, K. Kaneko, H. Mitsuhashi, Chem. Pharm. Bull. 35 (1987) 4460; (b) P.M. Hon, C.M. Lee, T.F. Choang, K.Y. Chui, H.N.C. Wong, Phytochemistry 29 (1990) 1189; (c) T. Naito, T. Katsuhara, K. Niitsh, Y. Ikeya, M. Okada, H. Mitsuhashi, Phytochemistry 31 (1992) 639. [2] (a) R.D. Barry, Chem. Rev. 64 (1964) 229; (b) S. Ohta, Y. Kamata, T. Inagaki, Y. Masuda, S. Yamamoto, M. Yamashita, I. Kawasaki, Chem. Pharm. Bull. 41 (1993) 1188. [3] (a) D. Villemin, D. Goussu, Heterocycles 29 (1989) 1255; (b) H.Y. Liao, C.-H. Cheng, J. Org. Chem. 60 (1995) 3711; (c) N.G. Kundu, M. Pal, B. Nandi, J. Chem. Soc., Perkin Trans. 1 (1998) 561. [4] S. Inack-Ngi, R. Rahmani, L. Commeiras, G. Chouraqui, J. Thibonnet, A. Duchene, M. Abarbri, J.-L. Parrain, Adv. Synth. Catal. 351 (2009) 779. [5] F. Bellina, D. Ciucci, P. Vergamini, R. Rossi, Tetrahedron 56 (2000) 2533. [6] E. Marchal, P. Uriac, B. Legouin, L. Toupet, P. van de Weghe, Tetrahedron 63 (2007) 9979. [7] X. Li, A.R. Chianese, T. Vogel, R.H. Crabtree, Org. Lett. 7 (2005) 5437. [8] (a) M. Uchiyama, H. Ozawa, K. Takuma, Y. Matsumoto, M. Yonehara, K. Hiroya, T. Sakamoto, Org. Lett. 8 (2006) 5517; (b) C. Kanazawa, M. Terada, Tetrahedron Lett. 48 (2007) 933. [9] (a) S. Elgafi, L.D. Field, B.A. Messerle, J. Organomet. Chem. 607 (2000) 97; (b) J.H.H. Ho, D.S. Black, B.A. Messerle, J.K. Clegg, P. Turner, Organometallics 25 (2006) 5800. [10] (a) B.A. Messerle, K.Q. Vuong, Organometallics 26 (2007) 3031; (b) J.H.H. Ho, R. Hodgson, J. Wagler, B.A. Messerle, Dalton Trans. (2010) 4062; (c) J.H.H. Ho, S. Choy, S.A. Macgregor, B.A. Messerle, Organometallics 30 (2011) 5978. [11] B.Y.-W. Man, M. Bhadbhade, B.A. Messerle, New J. Chem. 35 (2011) 1730. [12] W. Klaui, D. Schramm, G. Schramm, Inorg. Chim. Acta 357 (2004) 1642. [13] T. Rüther, M.C. Done, K.J. Cavell, E.J. Peacock, B.W. Skelton, A.H. White, Organometallics 20 (2001) 5522. [14] T. Rüther, N. Braussaud, K.J. Cavell, Organometallics 20 (2001) 1247. [15] A.J. Canty, J.M. Patrick, A.H. White, J. Chem. Soc., Dalton Trans. (1983) 1873. [16] L. Benisvy, S. Halut, B. Donnadieu, J.-P. Tuchagues, J.-C. Chottard, Y. Li, Inorg. Chem. 45 (2006) 2403. [17] T. Fjermestad, J.H.H. Ho, S.A. Macgregor, B.A. Messerle, D. Tuna, Organometallics 30 (2011) 618. [18] (a) H. Spiesecke, W.G. Schneider, Tetrahedron Lett. 14 (1961) 468; (b) K. Izawa, T. Okuyama, T. Fueno, Bull. Chem. Soc. Jpn. 46 (1973) 2881; (c) A.J. Amass, P.E. Brough, M.E. Colclough, I.M. Philbin, M.C. Perry, Des. Monomers Polym. 7 (2004) 413. [19] The Hammet constant provides a measure of the electronic nature of the substituent; a negative r value implies the substituent is electron donating, while a positive value implies the substituent is electron withdrawing C. Hansch, A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology, Wiley-Interscience, NY, 1979. [20] C.J. Moody, P. Shah, P. Knowles, J. Chem. Soc., Perkin Trans. 1 (1988) 3249. [21] (a) R. Mancuso, S. Mehta, B. Gabriele, G. Salerno, W.S. Jenks, R.C. Larock, J. Org. Chem. 75 (2010) 897; (b) M. Hellal, J.-J. Bourguignon, F.J.-J. Bihel, Tetrahedron Lett. 49 (2008) 62; (c) V. Subramanian, V.R. Batchu, D. Barange, M. Pal, J. Org. Chem. 70 (2005) 4778. [22] (a) R. Rossi, A. Carpita, F. Bellina, P. Stabile, L. Mannina, Tetrahedron 59 (2003) 2067; (b) H. Yang, G.-Y. Hu, J. Chen, Y. Wang, Z.-H. Wang, Bioorg. Med. Chem. Lett. 17 (2007) 5210.