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Methylenation of Aldehydes: Transition Metal Catalyzed Formation of Salt-Free Phosphorus Ylides

2001; Wiley; Volume: 40; Issue: 15 Linguagem: Inglês

10.1002/1521-3773(20010803)40

1521-3773

H. Lebel, Valérie Paquet, Caroline Proulx,

Phosphorus compounds and reactions

A variety of terminal alkenes are produced in excellent yields by the rhodium(I)-catalyzed methylenation of aldehydes using TMSCHN2 and PPh3 [Eq. (1)]. These mild reaction conditions allowed the conversion of enolizable substrates and the chemoselective methylenation of aldehydes over ketones. TMS=trimethylsilyl. Among the olefination processes,1 the methylenation of carbonyl derivatives is a very important transformation in synthesis.2 Recently even more attention has been devoted to this reaction since terminal alkenes are ideal precursors for ring-closing metathesis reactions.3 Although the Wittig reaction has been quite reliable for performing this transformation, several drawbacks are still associated with it. The most important problems include the low reactivity of the reagent with sterically hindered carbonyl derivatives as well as the possible epimerization of base-sensitive substrates.4 Several systems employing stoichiometric amounts of organometallic reagents have been developed to overcome these problems. For example, organometallic compounds based on titanium (Tebbe/Petasis) and zinc (Oshima/Lombardo) provide efficient methylenation of numerous carbonyl substrates.5 However, the use of stoichiometric amounts of expensive and in some cases pyrophoric compounds, as well as the competitive reductive coupling of aldehydes observed with these reagents,6 are undesired factors and indicate that there is still a significant need to develop new reagents to carry out this transformation. Few approaches to transition metal catalyzed olefinations have been disclosed, but they are all limited to the synthesis of α,β-unsaturated esters.7, 8 Numerous methods for the preparation of phosphorus ylides by deprotonation of phosphonium salts with a base have been reported.9 Conversely, sulfur, oxonium, nitrogen, carbonyl, and thiocarbonyl ylides have been successfully prepared from diazo compounds with the use of transition metal catalysts.10 However, with the exception of one report by Fujimura and Honma on the use of diazoacetate precursors,11 such a strategy has never been applied to the preparation of phosphorus ylides. Here we disclose the first transition metal catalyzed methylenation of aldehydes, based on the synthesis of salt-free phosphorus ylides from diazo reagents. In principle, the generation of Ph3P=CH2 (1) requires the use of CH2N2 as the diazo precursor (Scheme 1). Our first attempts at the methylenation of cinnamaldehyde (3) with CH2N2 using [RuCl(NO)(PPh3)2] as the catalyst were very disappointing (Table 1, entries 1, 2). No alkene product was observed, although [RuCl(NO)(PPh3)2] is known to produce stable carbene species in the presence of CH2N2.12 We also investigated TMSCHN2 (TMS=trimethylsilyl) as a safer alternative to CH2N2, since Ph3P=CHTMS can be rapidly desilylated in the presence of an alcohol to generate the corresponding salt-free phosphorus methylide.13, 14 The methylenation of 3 proceeded smoothly with TMSCHN2 in the presence of PPh3 and [RuCl(NO)(PPh3)2]. In the absence of an alcohol, diene 4 was produced quantitatively in 16 h (entry 3). In contrast, conversion was quantitative after 2 h when one equivalent of 2-propanol was added (entry 4). For comparison, only 45 % conversion was observed for the formation of α,β-unsaturated ester 5 under similar conditions with ethyl diazoacetate (EDA, entry 5). We then surveyed various catalysts for the methylenation of 3 with TMSCHN2, PPh3, and 2-propanol. Many ruthenium and rhodium complexes effectively catalyzed the methylenation with TMSCHN2 and 2-propanol, whereas low activity was often observed with EDA. The best catalytic activity was observed with Wilkinson's catalyst, [RhCl(PPh3)3], which allowed the quantitative conversion of 3 into diene 4 within 30 min at 25 °C with TMSCHN2 (entry 14). Again, the combination of TMSCHN2 and 2-propanol proved to be superior to CH2N2 and EDA (entries 12, 13). Under similar conditions, [{Rh(OAc)2}2] was inefficient at catalyzing the olefination of 3 (entries 23, 24). Generation of 1. Entry Catalyst[a] Diazo compound Conditions Conv. [%][b] (product) 1 [RuCl(NO)(PPh3)2] CH2N2 THF, 50 °C, 16 h ≤5 2 [RuCl(NO)(PPh3)2] CH2N2 benzene, 50 °C, 16 h ≤5 3 [RuCl(NO)(PPh3)2] TMSCHN2 THF, 50 °C, 16 h ≥98 (4) 4 [RuCl(NO)(PPh3)2] TMSCHN2 THF/iPrOH, 50 °C, 2 h ≥98 (4) 5 [RuCl(NO)(PPh3)2] EDA THF, 50 °C, 16 h 45 (5) 6 [RuCl2(PPh3)3] TMSCHN2 THF/iPrOH, 50 °C, 16 h ≥98 (4) 7 [RuCl2(PPh3)3] EDA THF, 50 °C, 8 h 92 (5)[c] 8 [Ru(NO)2(PPh3)2] TMSCHN2 THF/iPrOH, 50 °C, 16 h 90 (4) 9 [Ru(NO)2(PPh3)2] EDA THF, 50 °C, 16 h ≤5 10 [RuClCp(PPh3)2] TMSCHN2 THF/iPrOH, 50 °C, 16 h 90 (4) 11 [RuClCp(PPh3)2] EDA THF, 50 °C, 16 h 40 (5) 12 [RhCl(PPh3)3] CH2N2 THF, 25 °C, 16 h 60 (4) 13 [RhCl(PPh3)3] EDA THF, 25 °C, 16 h 60 (5) 14 [RhCl(PPh3)3] TMSCHN2 THF/iPrOH, 25 °C, 0.5 h ≥98 (4) 15 [RhCl(PPh3)3][d] TMSCHN2 THF/iPrOH, 25 °C, 0.5 h ≥98 (4) 16 [RhCl(PPh3)3] TMSCHN2 THF/iPrOH, 0 °C, 16 h 31 (4) 17 [RhCl(PPh3)3] TMSCHN2 THF/MeOH, 25 °C, 0.5 h 78 (4) 18 [RhCl(PPh3)3] TMSCHN2 THF/EtOH, 25 °C, 0.5 h 87 (4) 19 [RhCl(PPh3)3] TMSCHN2 THF/tBuOH, 25 °C, 0.5 h 16 (4) 20 [RhCl(PPh3)3] TMSCHN2 CH2Cl2/iPrOH, 25 °C, 1 h ≥98 (4) 21 [RhCl(PPh3)3] TMSCHN2 Et2O/iPrOH, 25 °C, 5 h ≥98 (4) 22 [RhCl(PPh3)3] TMSCHN2 toluene/iPrOH, 25 °C, 16 h ≥98 (4) 23 [{Rh(OAc)2}2] EDA THF, 25 °C, 16 h ≤5 24 [{Rh(OAc)2}2] TMSCHN2 THF/iPrOH, 25 °C, 16 h ≤5 The catalyst loading could be lowered to 2.5 mol % with no detrimental effect on the activity when [RhCl(PPh3)3] was used with TMSCHN2 and 2-propanol (Table 1, entry 15). Below this concentration, the reaction did not go to completion. Only 31 % conversion was observed when the reaction was carried out at 0 °C, (entry 16). 2-Propanol was the best alcohol surveyed (entries 14 vs 17–19). Although THF was the most effective solvent, equally high conversions were obtained in dichloromethane, diethyl ether, and toluene, but longer reaction times were required (entries 20–22). The reaction conditions used were quite general (Table 2). In all cases, terminal alkenes were isolated in excellent yields. Methylenation of the aromatic aldehyde 12 produced the styrene derivative 13 in 60 % yield (entry 5). This result is impressive since the highest yield reported so far for the synthesis of 13 was only 33 % using Lombardo's reagent.4f The sterically hindered aldehyde 14 reacted smoothly to produce alkene 15 in 79 % yield (entry 6). In contrast, 15 was isolated in only 40 % and 50 % yield when 1 was generated from 2 upon reaction with PhLi or sodium 1,1,1,3,3,3-hexamethyldisilazane (NaHMDS), respectively (see Scheme 1).15 Entry Substrate Product t [h] Yield [%][a] 1 0.5 88 2 7 84 3 8 91 4 1 98 5 0.5 60 6 7 79 7 0.5 87 8 1 86 9 1.5 79 10 5 74 11 4 86 12 3 89 The reaction can be performed in the presence of secondary amides (Table 2, entry 5), enolizable ketones (entry 7), or epoxides (entry 8), and a wide variety of protecting groups are compatible (silyl and benzyl ethers, acetonides, carbamates). The reaction with aldehyde 16 was highly chemoselective and resulted in the exclusive formation of 17 in 87 % yield (entry 7). For comparison, alkene 17 was isolated in only 59 % yield, along with product 28 in 15–20 % yield, when 16 was treated with 1 generated by deprotonation of 2 with NaHMDS [Eq. (1) ]. The new reaction conditions are mild and nonbasic, thus chiral nonracemic α-substituted aldehydes react without epimerization. The Garner's aldehyde 24 (93 % ee) was converted into 25 in 86 % yield and with 93 % ee (entry 11). Finally, aldehyde 26 afforded the terminal alkene 27 in 89 % yield while maintaining the stereochemical integrity of the adjacent chiral center (entry 12). These observations are in sharp contrast to the results obtained with non-lithium-free phosphorus ylides.4 In contrast to the reported methods of olefination based on decomposition of transition metal diazo compounds, it seems unlikely that the current reaction proceeds through a metal carbene intermediate. No reaction was observed when 3 was treated with the preformed metal carbene [CH2=RuCl(NO)(PPh3)2] obtained from CH2N2 and [RuCl(NO)(PPh3)2].12 In addition, no carbene was detected by spectroscopic methods when TMSCHN2 and 2-propanol were added to [RuCl(NO)(PPh3)2]. Rhodium(II) acetate, known for producing metal carbenes with diazo compounds, was inefficient at catalyzing the olefination reaction at room temperature. Finally, it is known that diazo compounds react with RhI through nitrogen complexation and the adduct does not produce carbene species.16 The proposed catalytic cycle involves the activation of the TMSCHN2 by [RhCl(PPh3)3] through nitrogen complexation. Nucleophilic attack by PPh3 followed by desilylation (mediated by 2-propanol) and nitrogen extrusion leads to the formation of Ph3P=CH2 (1) and regeneration of the catalyst. The formation of 1 was confirmed by 31P NMR spectroscopy when TMSCHN2 (1.0 equiv) was mixed with PPh3 (1.0 equiv), 2-propanol (1.0 equiv), and [RhCl(PPh3)3] (2.5 mol %). In conclusion, we have developed the first RhI-catalyzed methylenation of aldehydes using readily available reagents. The conditions are mild enough to be compatible with sensitive and enolizable substrates, thus highlighting the nonbasic character of phosphorus ylides in the absence of an inorganic component. Representative procedure: To a solution of [RhCl(PPh3)3] (0.023 g, 0.025 mmol) and PPh3 (0.577 g, 2.20 mmol) in THF (10 mL) was added 2-propanol (0.15 mL, 2.00 mmol) followed by the substrate (2.00 mmol). TMSCHN2 (1.75 mL, 2.80 mmol) was added to the resulting red mixture. Immediate gas evolution was observed, and the mixture was stirred at room temperature. Extraction and subsequent purification by flash chromatography provide the desired alkene. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.