Transition metal catalysed reactions of alcohols using

0 downloads 0 Views 367KB Size Report
alkenes. The return of hydrogen from the catalyst leads to the formation of new C–N and C–C bonds, ... including the addition of carbon-based nucleophiles (RMgX, RLi, etc.), alkene ... transfer reactions from the initial substrate to the final product. ... This aldehyde is then converted into an alkene 5 using a suitable in situ ...
www.rsc.org/dalton | Dalton Transactions

PERSPECTIVE

Transition metal catalysed reactions of alcohols using borrowing hydrogen methodology Tracy D. Nixon, Michael K. Whittlesey and Jonathan M. J. Williams* Received 1st August 2008, Accepted 23rd September 2008 First published as an Advance Article on the web 21st November 2008 DOI: 10.1039/b813383b The reactivity of alcohols can be enhanced by the temporary removal of hydrogen using a transition metal catalyst to generate an intermediate aldehyde or ketone. The so-formed carbonyl compound has a greater reactivity towards nucleophilic addition accommodating the in situ formation of imines or alkenes. The return of hydrogen from the catalyst leads to the formation of new C–N and C–C bonds, often with water as the only reaction by-product.

Introduction The chemistry of alcohols 1 is usually dominated by their nucleophilic oxygen, with relatively few synthetic methods, which do not rely on this reactivity. The borrowing hydrogen approach exploits the wider range of reactions available to carbonyl compounds 2 (Fig. 1). In particular, carbonyl compounds are usually good electrophiles, which undergo a range of transformations including the addition of carbon-based nucleophiles (RMgX, RLi, etc.), alkene formation (Wittig reaction, aldol condensation, etc.) and imine formation. Carbonyl compounds can also act as Cnucleophiles via the corresponding enols or enolates, whereas this pathway is not available to alcohols. The interconversion of alcohols and carbonyl compounds can be achieved using a wide range of oxidants and reductants. However, in the borrowing hydrogen approach, there is no net oxidation or reduction, with the chemistry relying on hydrogen transfer reactions from the initial substrate to the final product. For the formation of C–C bonds from an alcohol 3, a catalyst temporarily removes hydrogen to form the more reactive aldehyde 4. This aldehyde is then converted into an alkene 5 using a suitable in situ method (e.g. Wittig reaction or aldol condensation). The hydrogen is then returned, converting alkene 5 into the product 6 with the overall formation of a new C–C bond (Scheme 1). Depending on the choice of catalyst, the metal complex does not necessarily proceed via a dihydride, but the scheme illustrates the underlying concept involved in borrowing hydrogen. A closely related strategy may be used for the conversion of alcohols into amines, according to Scheme 2. The catalyst again temporarily removes hydrogen from the alcohol 3 to give an intermediate aldehyde 4. In the presence of an amine, the aldehyde is converted into imine 7, with return of the borrowed hydrogen providing the amine product 8. Alternative approaches to the formation of a new C–C or C–N bond from an alcohol typically involve conversion of the alcohol into an alkyl halide or other alkylating agent, followed by nucleophilic substitution with appropriate C- or N- nucleophiles. However, given the toxic/mutagenic nature of many alkylating Department of Chemistry, University of Bath, Claverton Down, Bath, UK BA2 7AY. E-mail: [email protected]; Fax: +44 1225 386231; Tel: +44 1225 383942

This journal is © The Royal Society of Chemistry 2009

Fig. 1 Carbonyl compounds have a wider range of reactivity than the corresponding alcohols.

Scheme 1

C–C bond formation by borrowing hydrogen.

Scheme 2

C–N bond formation by borrowing hydrogen.

agents, and the extra step required to generate them, the borrowing hydrogen pathway may offer environmental benefits over the traditional approach. Earlier reviews describing aspects of borrowing hydrogen chemistry (also called the hydrogen auto-transfer process) are available.1–3 This perspective is not intended to be comprehensive, Dalton Trans., 2009, 753–762 | 753

Tracy D. Nixon

Tracy Nixon was born in Newcastle-upon-Tyne in 1979 and graduated from the University of Leeds in 2001, where she then remained for her PhD under the supervision of Dr Terry Kee. After a two year postdoctoral position with Dr Jason Lynam at the University of York, she started work at the University of Bath in October 2007 as a postdoctoral research associate in the group of Prof. Jonathan Williams.

Mike Whittlesey was born in Nottingham in 1966. He received a DPhil in organometallic photochemistry with Prof. Robin Perutz and Dr Roger Mawby at the University of York, before moving to postdoctoral work in organic photochemistry with Prof. Tito Scaiano at the University of Ottawa, Canada. He returned to inorganic chemistry, working with Perutz at York once more on metal induced C–F bond Michael K. Whittlesey activation. After a fixed-term lectureship at the University of East Anglia, he moved to Bath in 1999, where he is now a senior lecturer. His research interests focus on the reactivity of transition metal-N-heterocyclic carbene complexes.

Jonathan Williams was born in Stourbridge in 1964. He received a BSc from the University of York, a DPhil from the University of Oxford (with Prof. S. G. Davies), and was then a postdoctoral fellow at Harvard with Prof. D. A. Evans (1989– 1991). He was appointed to a lectureship in organic chemistry at Loughborough University in 1991, and was then appointed as a professor of organic chemistry Jonathan M. J. Williams at the University of Bath in 1996, where his research has mainly involved the use of transition metals for the catalysis of organic reactions.

but will focus on the key reactions involving C–C and C–N bond formation proceeding through a borrowing hydrogen pathway, including as many recent examples as possible.

C–C Bond forming reactions The a-alkylation of ketones with alcohols has been widely investigated, with a number of homogeneous and heterogeneous catalysts being successful in this reaction. A general pathway for the alkylation of acetophenone 9 with benzyl alcohol 10 is given in Scheme 3. The initial removal of hydrogen from benzyl alcohol 10 generates benzaldehyde 11, which can then undergo an aldol condensation reaction with acetophenone 9 giving the a,b-unsaturated ketone 12. Return of the hydrogen leads to the saturated ketone 13. It has not been established whether this latter reduction process occurs via direct reduction of the C=C bond or via reduction of the ketone to give an allylic alcohol followed by isomerisation to the more stable ketone 13. 754 | Dalton Trans., 2009, 753–762

Scheme 3 Alkylation of acetophenone with benzyl alcohol.

Representative examples of the alkylation of ketones are given in Scheme 4. Cho, Shim and co-workers have used RuCl2 (PPh3 )3 This journal is © The Royal Society of Chemistry 2009

ketone 22 was isolated, presumably due to the preferential reaction of hydrogen with O2 rather than with the alkene. Several groups have reported a related process where a-alkylation of ketones leads to an alcohol as the final product, where the ketone has been reduced in the last step (Scheme 5). Cho and Shim have shown that in dioxane, their catalytic system results in the alkylation/reduction of ketones with alcohols.11 For example, the reaction of acetophenone 9 with n-butanol leads to the formation of alcohol 23. 1,4-Dioxane appears to be the source of the hydrogen required to form the product at the alcohol oxidation level. Yus and co-workers have suggested that excess alcohol could also act as the reducing agent.5 An interesting ketone alkylation followed by an asymmetric reduction procedure has been reported.12 In one example, acetophenone underwent a-alkylation with n-butanol using an iridium catalyst, followed by the addition of an enantiomerically pure ruthenium catalyst and isopropanol as the reducing agent. The isolated product (R)-23 was obtained with a good level of enantioselectivity.

Scheme 4 Alkylation reactions of ketones with alcohols.

with KOH to effect a range of ketone alkylations, including the alkylation of acetophenone 9 and tetralone 14 with benzyl alcohol 10.4 The addition of one equivalent of 1-dodecene was found to favour the formation of the ketone products 13 and 15, whereas without the alkene, the corresponding alcohol was also produced. Related chemistry has been reported by the group of Yus using Ru(dmso)4 Cl2 as an alternative catalyst.5,6 They achieved the formation of ketone 13 in 72% yield, with a higher yield obtained for the alkylation of ketone 16 to give the product 17. The iridium catalyst combination [Ir(cod)Cl]2 –PPh3 –KOH was also found to be an effective catalyst for the alkylation of ketones with primary alcohols.7 The observed regioselectivities when using unsymmetrical ketones were high, as seen in the alkylation of ketone 18 with n-butanol. There are also several examples of heterogeneous palladium catalysts used in related processes, including the use of palladium on carbon,8 palladium nanoparticles on a viologen polymer,9 and a highly reactive system involving palladium nanoparticles in aluminium hydroxide [Pd/AlO(OH)].10 With this latter system, a range of ketones were alkylated with various alcohols using just 0.2 mol% of catalyst. In the alkylation of ketone 20 with benzyl alcohol 10, the expected product 21 was obtained in a good yield. By performing the same reaction under an atmosphere of oxygen, the a,b-unsaturated This journal is © The Royal Society of Chemistry 2009

Scheme 5 Alkylation and reduction sequences leading to alcohols.

Ketones are not the only substrates that have been alkylated by alcohols using the borrowing hydrogen strategy. One of the earliest examples using homogeneous catalysis involved the a-alkylation of nitriles, reported by Grigg in 1981.13 More recently, Grigg and co-workers have reported the iridium-catalysed alkylation of arylacetonitriles, such as compound 24, with alcohols (Scheme 6).14 These reactions could also be performed using microwave irradiation leading to much shorter reaction times (10 min). The a-alkylation of nitriles using ruthenium-grafted hydrotalcite (Ru/HT) has also been shown to be effective,15 although more forcing reaction conditions were required. Thus, nitrile 24 was alkylated with n-butanol to give product 26 in 86% isolated yield. Various other substrates have undergone alkylation reactions with alcohols including nitroalkanes,16 barbituric acids,17 and various other active methylene compounds.16,18,19 Examples include the alkylation of the ester nitrile 27 with a range of alcohols, including 2-phenylethanol with a [Ir(cod)Cl]2 /PPh3 catalyst18 and the alkylation of ketonitrile 29 with benzyl alcohol using a catalyst Dalton Trans., 2009, 753–762 | 755

Scheme 7

Scheme 6 Alkylation reactions of other substrates.

combination19 comprising of Ru(PPh3 )3 (CO)H2 with the wide bite angle ligand xantphos.20 In the latter case, the xantphos ligand enhanced the reactivity of the catalyst, allowing for a catalyst loading of 0.5 mol% for alkylation reactions with benzylic alcohols. Grigg and co-workers have used indoles as less conventional nucleophiles in alkylation reactions with alcohols.21 The reaction of indole 31 with benzyl alcohol provided the 3-substituted product 32, which was believed to have been formed by the removal of hydrogen from benzyl alcohol to give benzaldehyde. Addition of the indole, elimination of water and return of the hydrogen then led to formation of the observed product. As well as the conversion of intermediate aldehydes into alkenes via condensation reactions, several other possibilities exist for this step. We have explored the use of an oxidation–Wittig reaction– reduction pathway using the borrowing hydrogen approach. Initially,22 we employed the [Ir(cod)Cl]2 /dppp combination23 to catalyse the reaction between benzyl alcohol and the phosphonium ylide 33 (Scheme 7). Whilst the expected product 34 of the oxidation–Wittig reaction–reduction sequence was formed, the reaction conditions were harsh and the reaction scope was somewhat limited. Our attention therefore turned to the use 756 | Dalton Trans., 2009, 753–762

Indirect Wittig reaction on alcohols.

of the more reactive ruthenium N-heterocyclic carbene (NHC) complexes, which are able to effect hydrogen transfer reactions between alcohols and alkenes.24 The Ru(NHC) complex 35 allowed the same transformation to be achieved under significantly milder conditions (80 ◦ C, 20 h).25 Complex 35 is initially activated by the addition of vinylsilane, which acts as a hydrogen acceptor to generate complex 36, which is then able to remove hydrogen from suitable alcohols, regenerating the dihydride complex 35. Complex 35 then delivers hydrogen back to the alkene, which is formed by the reaction of benzaldehyde with ylide 33. An examination of a range of Ru(NHC) complexes demonstrated that complex 37 was very well suited to catalysing this indirect Wittig reaction.26 Complex 37 was formed by the reaction of the N-heterocyclic carbene Ii Pr2 Me2 (1,3-bis-isopropyl-4,5dimethylimidazol-2-ylidene) with Ru(PPh3 )3 (CO)H2 . Rather than just a simple displacement of one of the phosphine ligands, as seen in the formation of complex 35, a spontaneous loss of H2 also occurred. Consequently, there was no requirement to preactivate complex 37 with vinylsilane and the catalyst proved to be more active (70 ◦ C, 2 h) for the conversion of benzyl alcohol and ylide 38 into the nitrile 39, along with related examples. In all of the examples detailed so far, the temporary conversion of an alcohol into a carbonyl compound has rendered the substrate more susceptible to nucleophilic addition. It has also This journal is © The Royal Society of Chemistry 2009

been possible to exploit the easy formation of enolates from the intermediate carbonyl compound. Our group has used this approach in the bromination of alcohols by borrowing hydrogen to generate a transient ketone.27 The reaction of alcohol 40 with the brominating agent pyridinium tribromide in the presence of aluminium t-butoxide led to the formation of the bromoalcohol 41 in a modest yield (Scheme 8). The reaction was believed to proceed via an alcohol-to-ketone-to-a-bromoketoneto-bromoalcohol pathway, where enolisation or enol formation was required for the bromination step to occur. Scheme 9 Combined activation of secondary and primary alcohols.

Scheme 8

Activation of alcohols to give enolate intermediates. Scheme 10

A similar strategy was used in an indirect nucleophilic addition to allylic alcohols, including the addition of methylmalononitrile 42 to cyclohexenol 43.28,29 The presence of an aluminium catalyst is required in order for the reaction to proceed, and is assumed to follow a borrowing hydrogen pathway. The oxidation of cyclohexenol 43 to cyclohexenone 45 allows the conjugate addition of nucleophile 42 to take place via the enolate 46. Protonation of this enolate leads to the conjugate addition product 47 and return of the hydrogen restores the alcohol function present in product 44. The use of the borrowing hydrogen methodology has been applied to the activation of two alcohols in one reaction sequence, according to Scheme 9. Both alcohols are converted into carbonyl compounds by the temporary removal of hydrogen. An aldol condensation then leads to the formation of an a,b-unsaturated ketone 48, which undergoes alkene reduction and ketone reduction by return of the hydrogen to give the saturated alcohol product 49. Cho, Shim and co-workers have alkylated a range of secondary alcohols with primary alcohols using a ruthenium-catalysed procedure. For example, alcohol 40 was alkylated with benzyl alcohol 10 to give product 50 (Scheme 10). 1-Dodecene acts as a hydrogen acceptor, and 1,4-dioxane as a hydrogen donor, and hence the process does not (exclusively) proceed via a borrowing hydrogen ´ and pathway.30 The RuCl2 (dmso)4 catalyst, favoured by Ramon This journal is © The Royal Society of Chemistry 2009

b-Alkylation of alcohols by alcohols.

Yus, is effective for the b-alkylation of secondary alcohols without the need for additional hydrogen donors or acceptors,31 providing access to alcohol 50 in 95% yield. Other benzylic secondary alcohols were also successful, including the alkylation of alcohol 40 with furfuryl alcohol 51 to give product 52 in an excellent isolated yield, although long reaction times were required. The [Cp*IrCl2 ]2 catalyst used by Fujita and Yamaguchi has also been used for these reactions,32 giving good yields for a wide range of substrates, with aliphatic secondary and primary alcohols being successful. For example, the alkylation of alcohol 53 with benzyl alcohol was achieved to provide product 54 in good yield. Other catalysts have recently been reported for this type of condensation reaction between alcohols.33 The condensation of primary alcohols has been referred to as the Guerbet condensation, after the first report of this process in 1909.34 Ishii and co-workers have recently reported the use of various iridium complexes for the catalysis of the selfcondensation of primary alcohols.35 Using [Cp*IrCl2 ]2 , 1-pentanol 55 was converted into 2-propyl-1-heptanol 56 with an almost quantitative conversion. Krische has developed elegant examples of processes which combine borrowing hydrogen with the addition of dienes,36 enynes37 and related nucleophiles38 to carbonyl compounds Dalton Trans., 2009, 753–762 | 757

(Scheme 11). 1,3-Cyclohexadiene 57 undergoes C–C bond formation with benzyl alcohol 10 to give the coupled product 58. Deuterium labelling studies reveal transfer of deuterium from the methylene group of the alcohol into the cyclohexene group in the product. The enyne 59 reacts via a similar pathway.

been a few reports involving the use of amides46,47 and related structures48 as substrates for N-alkylation reactions using borrowing hydrogen methodology. The most widely reported catalysts for alcohol amination using borrowing hydrogen methodology include those identified in Fig. 2. Some of the reactions catalysed by these complexes are outlined in the subsequent schemes.

Scheme 11 Krische’s alcohol functionalisation via carbonyl addition.

The standard borrowing hydrogen pathway can be intercepted by the addition of a hydrogen acceptor, which competes strongly for the hydrogen, limiting its return to the unsaturated intermediate. This was shown in Scheme 4, where oxygen acted as the hydrogen acceptor. We have recently demonstrated that crotononitrile 61 is a very efficient hydrogen acceptor when using the Ru(PPh3 )3 (CO)H2 –xantphos catalyst.39,40 The combination of benzyl alcohol with nitroethane 62 in the presence of crotononitrile 61 leads to the nitroalkene 63, with the ruthenium catalyst preferentially donating hydrogen to the crotononitrile rather than the nitroalkene. Using the malonate half ester 64, it is again an alkene that is formed. In this case, the reaction involves the loss of hydrogen to crotononitrile as well as the loss of carbon dioxide, generating the product as the a,b-unsaturated mono-ester 65 (Scheme 12).

Fig. 2

Examples of catalysts used for alcohol amination.

Fujita and Yamaguchi have used [Cp*IrCl2 ]2 66 in combination with K2 CO3 as an effective catalyst.49 The complex is commercially available and these researchers have published a detailed synthetic procedure using this catalyst in an amination reaction.50 There has also been a recent report on the mechanism derived from a DFT study.51 Representative examples of C–N bond forming reactions using this catalyst include the alkylation of aniline 71 with benzyl alcohol 10 to give N-benzylaniline 72 in quantitative conversion (Scheme 13).52 The reaction is also successful for the alkylation of alkylamines with primary and secondary alcohols as exemplified by the reaction of benzylamine 73 with cyclohexanol 74 to give the secondary amine product 75.53 The sequential,

Scheme 12 Intercepting the borrowing hydrogen pathway for the formation of alkenes from alcohols.

C–N Bond forming reactions Since the first examples of homogeneously catalysed N-alkylation of amines reported independently by Grigg41 and Watanabe,42 there have been many publications describing examples of catalysts and substrates for this process.2 Most of these reports have involved ruthenium or iridium catalysts, although there are some exceptions.43–45 The alkylation of primary and secondary amines, aliphatic and aromatic, have been reported, and there have also

Scheme 13 C–N bond formation using [Cp*IrCl2 ]2 .

758 | Dalton Trans., 2009, 753–762

This journal is © The Royal Society of Chemistry 2009

one-pot, addition of two alcohols to benzylamine led to the formation of tertiary amines bearing three different substituents. Multiple alkylation reactions were developed using this catalyst, as illustrated by the reaction of benzyl alcohol 10 with ammonium acetate to give tribenzylamine 76.54 Other alcohols similarly led to the corresponding trialkylamines, and interestingly, the use of ammonium tetrafluoroborate allowed selectivity for the formation of secondary amines. Alternative iridium catalysts have also been successful for the alkylation of amines by alcohols, including [Ir(cod)Cl]2 with dppf55 or [Ir(cod)Cl]2 with P, N-ligands such as Py2 NP(i Pr)2 .56 The reactions catalysed by Beller’s catalyst, Ru3 (CO)12 6757,58 and the [Ru(p-cymene)Cl2 ]2 complex 69 used in our own group59–61 are discussed in more detail. There are, however, several other ruthenium complexes that have been shown to be effective for alcohol amination including RuCl2 (PPh3 )3 ,62–64 RuCl3 ·nH2 O–3P(OBu)3 ,65 CpRu(PPh3 )2 Cl66 and [Ru(PPh3 )2 (MeCN)3 Cl][BPh4 ].67 Beller and co-workers have exploited the combination of Ru3 (CO)12 67 with sterically hindered phosphines for a range of alcohol amination reactions. It is the most active ruthenium-based catalyst for reactions involving the amination of secondary alcohols, such as the reaction of 1-phenylethanol 40 with hexylamine 77 (Scheme 14).57 In several cases, the use of ligand 68 proved to be beneficial and in the reaction of alcohol 79 with hexylamine, this allowed complete conversion into the product 80 with very good isolated yield.58

Scheme 15 Use of [Ru(p-cymene)Cl2 ]2 –diphosphine catalysts.

Scheme 16 Amines from alcohols and iminophosphoranes.

Scheme 14 Beller’s Ru3 (CO)12 67 catalyst in amination reactions.

We have found that the combination of [Ru(p-cymene)Cl2 ]2 69 with bidentate phosphines provides a catalytically active complex for the conversion of primary amines into secondary or tertiary amines. The reaction of alcohol 81 with enantiomerically pure amine 82 affords the product 83 in good yield and with no detectable erosion of enantiomeric excess (Scheme 15).59 Cyclic amines such as morpholine, piperidine and pyrrolidine have been alkylated with various primary alcohols, including the reaction of piperazine 84 with piperonyl alcohol 85 to give the dopamine agonist Piribedil 86.60 The use of volatile dimethylamine has also been successful for the conversion of alcohols into the corresponding N,N-dimethylamino compounds, including the conversion of alcohol 87 into Tripelennamine 88.61 Rather than using amines in the imine-forming step, we have demonstrated that iminophosphoranes may also be used.68 The reaction of benzyl alcohol 10 with iminophosphorane 89 led to the formation of amine 72 as the product (Scheme 16). The combination of [Ir(cod)Cl]2 with bidentate phosphines, such as dppf, was found to provide an active catalyst. The formation of This journal is © The Royal Society of Chemistry 2009

triphenylphosphine oxide as a by-product is a disadvantage of this procedure. In some cases, transamination reactions have been observed where one amine acts as the alkylating agent for another amine.69–71 In particular, Beller and co-workers have used the Shvo catalyst 90 in the alkylation of aniline 71 using hexylamine 77 as the alkylating agent (Scheme 17).72 Many other anilines were alkylated with other primary amines with good isolated yields under the same reaction conditions. The reaction is believed to occur via a

Scheme 17 Alkylation of aniline with amines.

Dalton Trans., 2009, 753–762 | 759

borrowing hydrogen pathway involving oxidation of hexylamine to an imine, which then undergoes transimination with aniline and loss of ammonia, followed by reduction to generate the product. In an extension of this work, dihexylamine and trihexylamine were also shown to be alkylating agents for aniline.73 The borrowing hydrogen strategy has been applied to the conversion of primary amines into N-heterocycles via a double alkylation process with suitable diols. The use of [Cp*IrCl2 ]2 for N-heterocyclisation was reported by Fujita and Yamaguchi,74 and was applied to the reaction of benzylamine and aniline with various diols to form 5-, 6- and 7-membered cyclic amines. For example, benzylamine 73 and 1,5-pentanediol 92 underwent conversion into piperidine 93 (Scheme 18). Subsequent applications of related chemistry have been reported,75 and extended to the reaction of diamine 94, which undergoes cyclisation with ethylene glycol to give the piperazine product 95.76 Ruthenium-catalysed reactions of diamines with diols have also been reported,77,78 as well as cyclisation reactions of diols, which contain additional heteroatoms.79,80 Such diols led to the formation of morpholines and piperazines, as shown in the conversion of various amines 96 with diols 97 leading to the cyclisation products 98. The ruthenium catalysts used included RuCl2 (PPh3 )3 as well as cationic complexes with terdentate PNP ligands.

Scheme 19 Formation of furans and pyrroles by an isomerisation–condensation pathway.

whereas the presence of a primary amine is a requirement for pyrrole formation. Amongst the alternative approaches to the formation of N-heterocycles, Cho, Shim and co-workers have reported an interesting approach to the formation of quinolines using various ruthenium catalysts.85,86 Alcohol 103 reacts with acetophenone 9 (and a wide range of other ketones) using first generation Grubbs catalyst 104 (Scheme 20). The quinoline 105 is formed by an oxidative process with formal loss of hydrogen. Alternative ruthenium87–89 and iridium90 catalysts have been employed for the same transformation, in some cases starting from an alcohol rather than a ketone. The reaction of o-phenylenediamine 106 with diol 107 under ruthenium-catalysed oxidative conditions led to the formation of quinoxaline 108.91

Scheme 18 N-heterocyclisation reactions of amines.

As well as the formation of saturated N-heterocycles from amines, there have been many reports involving the formation of various aromatic heterocycles, where hydrogen transfer is a key feature of the mechanism. The use of 1,4-alkynediols has been exploited in the preparation of furans81 and pyrroles,82 including our own work in this area.83,84 It seems likely that the 1,4-alkynediol is isomerised to a 1,4-dicarbonyl compound by the transition metal catalyst, and that there is a subsequent conversion into either the furan or the pyrrole. However, it is also possible that for pyrrole formation, N-alkylation of the amine by the 1,4-alkynediol occurs prior to cyclisation. Examples of these processes include the conversion of alkynediol 99 into the furan 100 as well as alkynediol 101 into the pyrrole 102 depending on the reaction conditions (Scheme 19). The presence of an acid assists with furan formation, 760 | Dalton Trans., 2009, 753–762

Scheme 20 N-heterocycles by oxidative cyclisation reactions.

Indole 31 has been prepared from alcohol 109 by loss of hydrogen and cyclisation. This process was first reported by Watanabe in 1990 using RuCl2 (PPh3 )3 as the catalyst.92 In the presence of a hydrogen donor, it was also possible to start from the nitroarene in place of the amine in compound 109. Fujita and Yamaguchi reported that their [Cp*IrCl2 ]2 /K2 CO3 catalyst was also effective for this indole forming reaction.93 This journal is © The Royal Society of Chemistry 2009

Conclusions The borrowing hydrogen methodology provides a useful alternative to conventional alkylation reactions for the formation of C–C and C–N bonds. Catalysts temporarily remove hydrogen from the alcohol substrate to provide an aldehyde or ketone intermediate, which readily undergoes either alkene or imine formation. Return of the hydrogen leads to an overall redox neutral process, often with water as the only by-product. This methodology is being applied to a growing number of substrates and appears to have a fairly good tolerance of other functional groups. Currently, the available catalysts have not been able to function at ambient temperature and this is a worthwhile objective for future research in the area.

Acknowledgements We thank the EPSRC for funding through grant EP/E065392/1.

Notes and references 1 M. H. S. A. Hamid, P. A. Slatford and J. M. J. Williams, Adv. Synth. Catal., 2007, 349, 1555. 2 G. W. Lamb and J. M. J. Williams, Chim. Oggi, 2008, 26(3), 17. ´ and M. Yus, Angew. Chem., Int. Ed., 2007, 3 G. Guillena, D. J. Ramon 46, 2358. 4 C. S. Cho, B. T. Kim, T.-J. Kim and S. C. Shim, Tetrahedron Lett., 2002, 43, 7987. ´ and M. Yus, Tetrahedron Lett., 5 R. Mart´ınez, G. J. Brand, D. J. Ramon 2005, 46, 3683. ´ and M. Yus, Tetrahedron Lett., 6 R. Mart´ınez, G. J. Brand, D. J. Ramon 2006, 62, 8988. 7 K. Taguchi, H. Nakagawa, T. Hirabayashi, S. Sakaguchi and Y. Ishii, J. Am. Chem. Soc., 2004, 126, 72. 8 C. S. Cho, J. Mol. Catal. A: Chem., 2005, 240, 55. 9 Y. M. A. Yamada and Y. Uozumi, Org. Lett., 2006, 8, 1375. 10 M. S. Kwon, N. Kim, S. H. Seo, I. S. Park, R. K. Cheedrala and J. Park, Angew. Chem., Int. Ed., 2005, 44, 6913. 11 C. S. Cho, B. T. Kim, T.-J. Kim and S. C. Shim, J. Org. Chem., 2001, 66, 9020. 12 G. Onodera, Y. Nishibayashi and S. Uemura, Angew. Chem., Int. Ed., 2006, 45, 3819. 13 R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit and N. Tongpenyai, Tetrahedron Lett., 1981, 22, 4107. ¨ 14 C. Lofberg, R. Grigg, M. A. Whittaker, A. Keep and A. Derrick, J. Org. Chem., 2006, 71, 8023. 15 K. Motokura, D. Nishimura, K. Mori, T. Mizugaki, K. Ebitani and K. Kaneda, J. Am. Chem. Soc., 2004, 126, 5662. 16 P. J. Black, G. Cami-Kobeci, M. G. Edwards, P. A. Slatford, M. K. Whittlesey and J. M. J. Williams, Org. Biomol. Chem., 2006, 4, 116. ¨ 17 C. Lofberg, R. Grigg, A. Keep, A. Derrick, V. Sridharan and C. Kilner, Chem. Commun., 2006, 5000. 18 M. Morita, Y. Obora and Y. Ishii, Chem. Commun., 2007, 2850. 19 P. A. Slatford, M. K. Whittlesey and J. M. J. Williams, Tetrahedron Lett., 2006, 47, 6787. 20 Z. Freixa and P. W. N. M. van Leeuwen, Dalton Trans., 2003, 1890. 21 S. Whitney, R. Grigg, A. Derrick and A. Kepp, Org. Lett., 2007, 9, 3299. 22 M. G. Edwards and J. M. J. Williams, Angew. Chem., Int. Ed., 2002, 41, 4740. 23 S. Sakaguchi, T. Yamaga and Y. Ishii, J. Org. Chem., 2001, 66, 4710. 24 (a) S. Burling, M. K. Whittlesey and J. M. J. Williams, Adv. Synth. Catal., 2005, 347, 591; (b) R. F. R. Jazzar, S. A. Macgregor, M. F. Mahon, S. P. Richards and M. K. Whittlesey, J. Am. Chem. Soc., 2002, 124, 4944 . 25 M. G. Edwards, R. F. R. Jazzar, B. M. Paine, D. J. Shermer, M. K. Whittlesey, J. M. J. Williams and D. D. Edney, Chem. Commun., 2004, 90.

This journal is © The Royal Society of Chemistry 2009

26 S. Burling, B. M. Paine, D. Nama, V. S. Brown, M. F. Mahon, T. J. Prior, P. S. Pregosin, M. K. Whittlesey and J. M. J. Williams, J. Am. Chem. Soc., 2007, 129, 1987. 27 G. Cami-Kobeci and J. M. J. Williams, Synlett, 2003, 124. 28 P. J. Black, W. Harris and J. M. J. Williams, Angew. Chem., Int. Ed., 2001, 40, 4475. 29 P. J. Black, M. G. Edwards and J. M. J. Williams, Tetrahedron, 2005, 61, 1363. 30 C. S. Cho, B. T. Kim, H.-S. Kim, T.-J. Kim and S. C. Shim, Organometallics, 2003, 22, 3608. ´ and M. Yus, Tetrahedron, 2006, 62, 8982. 31 R. Mart´ınez, D. J. Ramon 32 K.-I. Fujita, C. Asai, T. Yamaguchi, F. Hanasaka and R. Yamaguchi, Org. Lett., 2005, 7, 4017. 33 M. Viciano, M. Sanau and E. Peris, Organometallics, 2007, 26, 6050; A. P. da Costa, M. Viciano, M. Sanau, S. Merino, J. Tejeda, E. Peris and B. Royo, Organometallics, 2008, 27, 1305. 34 M. C. R. Guerbet, Acad. Sci., 1909, 49, 129; C. Carlini, M. Di Girolamo, A. Macinai, M. Marchionna, M. Noviello, A. M. Raspolli Galletti and G. Sbrana, J. Mol. Catal. A: Chem., 2003, 204–205, 721. 35 T. Matsu-ura, S. Sakaguchi, Y. Obora and Y. Ishii, J. Org. Chem., 2006, 71, 8306. 36 J. F. Bower, R. L. Patman and M. J. Krische, Org. Lett., 2008, 10, 1033. 37 R. L. Patman, V. M. Williams, J. F. Bower and M. J. Krische, Angew. Chem., Int. Ed., 2008, 47, 5220. 38 M.-Y. Ngai, E. Skucas and M. J. Krische, Org. Lett., 2008, 10, 2705. 39 M. I. Hall, S. J. Pridmore and J. M. J. Williams, Adv. Synth. Catal., 2008, 350, 1975. 40 N. A. Owston, A. J. Parker and J. M. J. Williams, Chem. Commun., 2008, 624. 41 R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakitt and N. Tongpenyai, J. Chem. Soc., Chem. Commun., 1981, 611. 42 Y. Watanabe, Y. Tsuji and Y. Ohsugi, Tetrahedron Lett., 1981, 22, 2667. 43 Y. Tsuji, R. Takeuchi, H. Ogawa and Y. Watanabe, Chem. Lett., 1986, 293. 44 Y. Shvo and R. M. Laine, J. Chem. Soc., Chem. Commun., 1980, 753. 45 D. M. Roundhill, Chem. Rev., 1992, 92, 1. 46 Y. Watanabe, T. Ohta and Y. Tsuji, Bull. Chem. Soc. Jpn., 1983, 56, 2647. 47 G. Jenner, J. Mol. Catal., 1989, 55, 241. 48 T. Kondo, S. Kotachi and Y. Watanabe, J. Chem. Soc., Chem. Commun., 1992, 1318. 49 K.-I. Fujita and R. Yamaguchi, Synlett, 2005, 4, 560. 50 K.-I. Fujita, Y. Enoki and R. Yamaguchi, Org. Synth., 2006, 83, 217. 51 D. Balcells, A. Nova, E. Clot, D. Gnanamgari, R. H. Crabtree and O. Eisenstein, Organometallics, 2008, 27, 2529. 52 K.-I. Fujita, Z. Li, N. Ozeki and R. Yamaguchi, Tetrahedron Lett., 2003, 44, 2687. 53 K.-I. Fujita, Y. Enoki and R. Yamaguchi, Tetrahedron, 2008, 64, 1943. 54 R. Yamaguchi, S. Kawagoe, C. Asai and K.-I. Fujita, Org. Lett., 2008, 10, 181. 55 G. Cami-Kobeci, P. A. Slatford, M. K. Whittlesey and J. M. J. Williams, Bioorg. Med. Chem. Lett., 2005, 15, 535. 56 B. Blank, M. Madalska and R. Kempe, Adv. Synth. Catal., 2008, 350, 749. 57 A. Tillack, D. Hollmann, D. Michalik and M. Beller, Tetrahedron Lett., 2006, 47, 8881. 58 D. Hollmann, A. Tillack, D. Michalik, R. Jackstell and M. Beller, Chem.–Asian J., 2007, 2, 403. 59 M. H. S. A. Hamid and J. M. J. Williams, Chem. Commun., 2007, 725. 60 M. H. S. A. Hamid and J. M. J. Williams, Tetrahedron Lett., 2007, 48, 8263. 61 M. H. S. A. Hamid, and J. M. J. Williams, unpublished results. 62 Y. Watanabe, Y. Tsuji, H. Ige, Y. Ohsugi and T. Ohta, J. Org. Chem., 1984, 49, 3359. 63 Y. Watanabe, Y. Morisaki, T. Kondo and T.-A. Mitsudo, J. Org. Chem., 1996, 61, 4214. 64 S. Ganguly and D. M. Roundhill, Polyhedron, 1990, 20, 2517. 65 K.-T. Huh, Y. Tsuji, M. Kobayashi, F. Okuda and Y. Watanabe, Chem. Lett., 1988, 449. 66 A. Del Zotto, W. Baratta, M. Sandri, G. Verardo and P. Rigo, Eur. J. Inorg. Chem., 2004, 524. 67 S. Naskar and M. Bhattacharjee, Tetrahedron Lett., 2007, 48, 3367. 68 G. Cami-Kobeci and J. M. J. Williams, Chem. Commun., 2004, 1072. 69 A. Miyazawa, K. Saitou, K. Tanaka, T. M. G¨adda, M. Tashiro, G. K. Prakash and G. A. Olah, Tetrahedron Lett., 2006, 47, 1437.

Dalton Trans., 2009, 753–762 | 761

70 Bui-The-Khai, C. Concilio and G. Porzi, J. Organomet. Chem., 1981, 208, 249; Bui-The-Khai, C. Concilio and G. Porzi, J. Org. Chem., 1981, 46, 1759; C. W. Jung, J. D. Fellman and P. E. Garrou, Organometallics, 1983, 2, 1042. 71 Y. Shvo and R. M. Laine, J. Chem. Soc., Chem. Commun., 1980, 753. 72 D. Hollmann, S. B¨ahn, A. Tillack and M. Beller, Angew. Chem., Int. Ed., 2007, 46, 8291. 73 D. Hollmann, S. B¨ahn, A. Tillack and M. Beller, Chem. Commun., 2008, 3199. 74 K.-I. Fujita, T. Fujii and R. Yamaguchi, Org. Lett., 2004, 6, 3525. 75 C. T. Eary and D. Clasen, Tetrahedron Lett., 2006, 47, 6899. 76 L. U. Nordstrøm and R. Madsen, Chem. Commun., 2007, 5034. 77 K.-T. Huh, S. C. Shim and C. H. Doh, Bull. Korean Chem. Soc., 1990, 11, 45. 78 J. A. Marsella, J. Organomet. Chem., 1991, 407, 97. 79 Y. Tsuji, K.-T. Huh, Y. Ohsugi and Y. Watanabe, J. Org. Chem., 1985, 50, 1365. 80 R. A. T. M. Abbenhuis, J. Boersma and G. van Koten, J. Org. Chem., 1998, 63, 4282. 81 J. Ji and X. Lu, J. Chem. Soc., Chem. Commun., 1993, 764.

762 | Dalton Trans., 2009, 753–762

82 Y. Tsuji, Y. Yokoyama, K.-T. Huh and Y. Watanabe, Bull. Chem. Soc. Jpn., 1987, 60, 3456. 83 S. J. Pridmore, P. A. Slatford and J. M. J. Williams, Tetrahedron Lett., 2007, 48, 5111. 84 S. J. Pridmore, P. A. Slatford, A. Daniel, M. K. Whittlesey and J. M. J. Williams, Tetrahedron Lett., 2007, 48, 5115. 85 C. S. Cho, B. T. Kim, T.-J. Kim and S. C. Shim, Chem. Commun., 2001, 2576. 86 C. S. Cho, B. T. Kim, H.-J. Choi, T.-J. Kim and S. C. Shim, Tetrahedron, 2003, 59, 7997. 87 K. Motokura, T. Mizugaki, K. Ebitani and K. Kaneda, Tetrahedron Lett., 2004, 45, 6029. 88 C. S. Cho, W. X. Ren and S. C. Shim, Bull. Korean Chem. Soc., 2005, 26, 2038. ´ and M. Yus, Eur. J. Org. Chem., 2007, 1599. 89 R. Mart´ınez, D. J. Ramon 90 K. Taguchi, S. Sakaguchi and Y. Ishii, Tetrahedron Lett., 2005, 46, 4539. 91 C. S. Cho and S. G. Oh, Tetrahedron Lett., 2006, 47, 5633. 92 Y. Tsuji, S. Kotachi, K.-T. Huh and Y. Watanabe, J. Org. Chem., 1990, 55, 580. 93 K.-I. Fujita, K. Yamamoto and R. Yamaguchi, Org. Lett., 2002, 4, 2691.

This journal is © The Royal Society of Chemistry 2009