Kristine
Müther
and
Martin
Oestreich
*
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstrasse 40, D-48149 Münster, Germany. E-mail: martin.oestreich@uni-muenster.de; Fax: +49 (0)25183-36501; Tel: +49 (0)25183-33271
First published on 25th August 2010
The silylium ion-catalysed reduction of carbonyl compounds to the alcohol oxidation level is accomplished by exploiting the unique reactivity of a ferrocenyl-substituted silane.
The situation is different in the silylium ion-catalysed reduction of carbonyl compounds,7 resulting in deoxygenation rather than reduction to the alcohol oxidation level. Kira et al. had investigated that unexpected outcome almost two decades ago,8 and an investigation by Piers et al. later corroborated the suggested mechanism (Scheme 1).9 The catalysis commences with the formation of silyloxycarbenium (or silylcarboxonium) ion 3 through coordination of the Lewis basic carbonyl oxygen of 2 to donor-stabilised silylium ion 1. The hydride affinity of 3 is not as pronounced as that of the previously discussed carbenium ions,10 and hydride abstraction from silane 4 will be less facile. Piers et al. had reasoned though that hydride transfer is likely to be assisted by the oxygen atom in 3,9 proceeding through tentative transition state 5 (3 → 6). Disiloxane 7 is a good leaving group, and oxonium ion 6 dissociates to produce carbenium ion 8, which in turn is sufficiently reactive to directly regenerate silylium ion 1 upon reaction with 4 (8 → 9). The net deoxygenation (2 → 9) was experimentally verified at room temperature for benzophenone8 and acetophenone9 as substrates.11
Scheme 1 The Kira–Piers mechanism of the silylium ion-catalysed deoxygenation of carbonyl compounds (Do = donor and R = Et). Counteranion [BAr4]− is omitted for clarity (Ar = 3,5-bis(trifluoromethyl)phenyl8 or pentafluorophenyl9). |
Aside from the hydride affinity of an intermediate silylcarboxonium ion, the hydride donor strength of the silane is equally critical. Our laboratory recently introduced ferrocene-stabilised silylium ion 11,12,13 which was accessed by an exceptionally rapid Bartlett–Condon–Schneider hydride transfer14 (10 → 11, Scheme 2).
We then anticipated that the unusual hydridic character of 10 could allow for the reduction of silylcarboxonium ion 12 without concomitant oxonium ion formation (12 → 13, Scheme 3). Both the stabilisation of the trivalent silicon cation through the ferrocenyl substituent and the steric bulk of the reaction partners might account for immediate regeneration of “free” 11. In this communication, we report the silylium ion-catalysed reduction of carbonyl compounds, which hinges upon the self-regeneration of a catalytically active silicon cation by that mechanism (2 → 13, Scheme 3).
Scheme 3 Proposed silylium ion-catalysed reduction of carbonyl compounds. Counteranion [B(C6F5)4]− is omitted for clarity. |
In light of the deoxygenation observed for aryl-substituted ketones (vide supra),8,9 we began our screening using these carbonyl compounds. Catalyst 11 was generated in CH2Cl2 at −60 °C from [Ph3C]+[B(C6F5)4]− (5.0 mol%) and a slight excess of 10 prior to addition of the reactants (Scheme 4).§ The reaction of acetophenone was smooth, affording the silicon ether in good yield (2a → 13a, Table 1, entry 1). No defunctionalisation was detected. Conversely, benzophenone was not participating in the catalysis at all (2b, Table 1, entry 2). This rather unexpected result might be explained by the relative hydride affinities of silylcarboxonium ions 12a and 12b (cf.Scheme 3): two phenyl groups (as in 12b) lend more stabilization to such intermediates than just one (as in 12a). The same rationale applies to naphthyl- and other electron-rich phenyl-substituted ketones (2c–2f, Table 1, entries 3–6).
Entry | Carbonyl compound 2 | Silicon ether 13 | ||||
---|---|---|---|---|---|---|
No. | R1 | R2 | No. | drb | Yieldc (%) | |
a All reactions were conducted using [Ph3C]+[B(C6F5)4]− (5.0 mol%) to generate 11, and silane (1.2 equiv.) and carbonyl compound (1.0 equiv.) with a ketone concentration of 0.2 M in CH2Cl2 at −60 °C. Reactions were terminated after 2½ h. b Diastereomeric ratio determined by GLC analysis prior to purification. c Combined yield of analytically pure mixture of diastereomers after flash chromatography. d Details are discussed in the text (Scheme 5). e Poor reactivity also due to steric factors. | ||||||
1 | 2a | Ph | Me | 13a | 51∶49 | 82 |
2 | 2b | Ph | Ph | 13b | — | No reaction |
3 | 2c | 2-C10H7 | Me | 13c | — | Tracesd |
4 | 2d | 1-C10H7 | Me | 13d | — | No reactione |
5 | 2e | 4-MeOC6H4 | Me | 13e | — | No reaction |
6 | 2f | 4-MeC6H4 | Me | 13f | 52∶48 | 10d |
7 | 2g | 2-ClC6H4 | Me | 13g | 78∶22 | 97 |
8 | 2h | C6F5 | Me | 13h | 52∶48 | 85 |
9 | 2i | Ph | Et | 13i | 78∶22 | 82 |
Only 2g–2i displayed the reactivity of 2a (2g–2i → 13g–13i, Table 1, entries 7–9), and the slightly more hindered substrates 2g and 2i showed a low level of diastereocontrol. The lack of facial selectivity might be interpreted in support of the hypothesis that silicon-to-carbon hydride transfer passes through an acyclic transition state (12 → 13, Scheme 3),15 not involving the oxygen atom (cf.4 → 5 → 6, Scheme 1).
The poor reactivity of ketones 2b–2f might be overcome at elevated reaction temperatures. The upper temperature limit of −30 °C is set by the chemical stability of silylium ion 11 in CH2Cl2.12 However, even an increase from −60 °C to −45 °C partially resulted in ipsoalkylation of the ferrocene in several cases (10 → 14, Scheme 5). We further analyzed this finding in the reduction of acetophenone at −45 °C: the silicon ether formed in the carbonyl-to-hydroxy reduction (2a → 13a) was readily converted into the alkylated ferrocene in 55% isolated yield (13a → 14a). Treatment of an independently prepared sample of 13a under the standard reaction conditions at −45 °C afforded 14a in 38% isolated yield. This set of data indicates to us that reduction occurs at higher reaction temperatures, followed by carbenium ion formation (cf.Scheme 1). The thus formed strong electrophile is then attacked by any of the present silylated ferrocenes, e.g., 13 or (tBuFcMeSi)2O (Fc = ferrocenyl), to undergo a Friedel–Crafts reaction.
Scheme 5 Deoxygenation—Friedel–Crafts sequence {[Ph3C]+[B(C6F5)4]− (5.0 mol%) was used to initiate the reaction}. |
These experiments clearly reveal that the stability or, more precisely, the hydride affinity of the intermediate silylcarboxonium ion profoundly effects this catalysis. Electron-rich 4-MeOC6H4 (as in 2e) is deactivating, electron-poor C6F5 (as in 2h) is activating (Table 1, entries 5 and 8). The majority of aryl-substituted substrates forms unreactive 12 (Scheme 3 and Table 1). Based on this understanding, we expected 12 derived from purely alkyl-substituted carbonyls to be less stable and more reactive, and this is indeed the case. All dialkyl ketones surveyed performed very well (2j–2p → 13j–13p, Table 2). Diastereoselectivity was again low (vide supra).15
Entry | Carbonyl compound 2 | Silicon ether 13 | ||||
---|---|---|---|---|---|---|
No. | R1 | R2 | No. | drb | Yieldc (%) | |
a All reactions were conducted using [Ph3C]+[B(C6F5)4]− (5.0 mol%) to generate 11, and silane (1.2 equiv.) and carbonyl compound (1.0 equiv.) with a ketone concentration of 0.2 M in CH2Cl2 at −60 °C. Reactions were terminated after 2½ h. b Diastereomeric ratio determined by GLC analysis prior to purification. c Combined yield of analytically pure mixture of diastereomers after flash chromatography. | ||||||
1 | 2j | –(CH2)4– | 13j | — | 85 | |
2 | 2k | –(CH2)5– | 13k | — | 95 | |
3 | 2l | –(CH2)11– | 13l | — | 86 | |
4 | 2m | Et | Et | 13m | — | 79 |
5 | 2n | Et | Me | 13n | 50∶50 | 44 |
6 | 2o | iBu | Me | 13o | 60∶40 | 79 |
7 | 2p | tBu | Me | 13p | 58∶42 | 77 |
These results are in contrast to the work of Kira et al.;8silylium ion-catalysed reduction of cyclododecanone (2l) afforded neither 13l nor cyclododecane but cyclododecene in high yield.11
To recap, we disclosed here an unprecedented silylium ion-catalysed reduction of carbonyl compounds, in which any of the previously reported deoxygenation pathways8,9 are suppressed. The hydride donor strength of our ferrocenyl-substituted silane is the decisive feature, allowing for the hydride transfer onto rather unreactive silylcarboxonium ions at low temperature. The reduction step itself regenerates the catalytically active trivalent silicon cation.
K.M. thanks the Studienstiftung des deutschen Volkes for a predoctoral fellowship (2009–2011). K.M. is a member of the International Research Training Group Münster–Nagoya (GRK 1143 of the Deutsche Forschungsgemeinschaft).
Footnotes |
† This article is part of the ‘Emerging Investigators’ themed issue for ChemComm. |
‡ Electronic supplementary information (ESI) available: Preparation and characterisation data as well as 1H, 13C, 19F and 29Si NMR spectra of all new compounds. See DOI: 10.1039/c0cc02139c |
§ General procedure for the silylium ion-catalysed carbonylreduction: in a glove-box, a flame-dried 10 mL Schlenk tube equipped with a magnetic stir bar is charged with [Ph3C]+[B(C6F5)4]− (9.2 mg, 0.010 mmol, 5.0 mol%). The Schlenk tube is transferred to a fume cupboard and connected to an argon–vacuum manifold. Addition of dry CH2Cl2 (1.0 mL) results in a yellow solution, which is subsequently cooled to −60 °C using an ethanol cooling bath and a cryostat. After silane addition (10, 11 mg, 0.040 mmol, 0.20 equiv.), the now brown solution is stirred for 10 min, followed by successive addition of the carbonyl compound 2 (0.20 mmol, 1.0 equiv.) and the silane 10 (57 mg, 0.20 mmol, 1.0 equiv.) dissolved in dry CH2Cl2 (0.5 mL each). The reaction mixture is maintained at −60 °C for 2½ h, and the reaction is then terminated by the addition of dry hexane (10 mL), pre-cooled to −60 °C. Filtration over a small pad of Celite® and evaporation of the solvents under reduced pressure affords crude 13, which is further purified by flash chromatography on silica gel using cyclohexane as eluent. The diastereomeric ratio is determined by GLC analysis prior to purification. |
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