Silylformylation aldehydes

Silylformylation, defined as the addition of RsSi- and -CHO across various types of bonds using a silane R3SiH, CO, and a transition metal catalyst, was discovered by Murai and co-workers, who developed the Co2(CO)8-catalyzed silylformylation of aldehydes, epoxides, and cyclic ethers [26]. More recently, as described in detail in Section 5.3.1, below, alkynes and alkenes have been successfully developed as silylformylation substrates. These reactions represent a powerful variation on hydroformylation, in that a C-Si bond is produced instead of a C-H bond. Given that C-Si groups are subject to, among other reactions, oxidation to C-OH groups, silylformylation could represent an oxidative carbonylation of the type described in Scheme 5.1. 

The development of the first alkyne silylformylation reaction was reported in 1989 by Matsuda [27]. Alkynes were treated with Me2PhSiH and Et3N with 1 mol% Rh4(CO)i2 under CO pressure to produce yS-silyl-a,/ -unsaturated aldehydes (Scheme 5.20). A second report from Ojima detailed the development of rhodium-cobalt mixed metal clusters as effective catalysts for alkyne silylformylation [28]. Shortly thereafter, Doyle reported that rhodium(II) perfluorobutyrate was a highly efficient and selective catalyst for alkyne silylformylation under remarkably mild reaction conditions (0°C, 1 atm CO) [29]. In all these reports, terminal alkynes react regiospedfically with attachment of the silane to the unsubstituted end of the alkyne. The reaction is often (but not always) stereospecific, producing the cis-product preferentially. 

One of the important advantages of the intramolecular alkene silylformylation reaction as an aldol equivalent is that the products are masked 3,5-dihydroxyalkanals, and therefore that no manipulations are required prior to iteration of the process by aldehyde al-lylation to set up the next intramolecular silylformylation. Given that allylsilanes are well-known aldehyde allylation reagents, intramolecular silylformylation employing a diallylhydrosilane would, in principle, allow for the possibility of a tandem silylformyla-tion/allylsilylation reaction. This has been reduced to practice the diaUylsilyl ethers 60 were subjected to the previously developed silylformylation conditions and the unpuri-fied reaction mixtures were subjected to the Tamao oxidation ]36] to provide triols 61... 

Silylformylation and hydroformylation reactions figured prominently in Ojima s approach to isoretronecanol and trachelanthamidine [40]. Thus, silylformylation of alkyne 70 proceeded smoothly to produce aldehyde 71 (Scheme 5.26). Reduction and protodesilylation provided allylic alcohol 72, which was protected to give 73. Hydroformylation in the presence of HC(OEt)3 led to a 2 1 mixture of 74 and 75. Deprotection and amide and amidal reduction then provided the target compounds. 

The vast majority of the work described in this chapter was reported since 1995. Rho-dium( I)-catalyzed hydroformylation and silylformylation reactions have only very recently been adapted and developed for use in the efficient synthesis of stereochemi-cally complex natural products. In addition, the recent development of tandem reactions that take advantage of the direct production of aldehydes in these carbonylation reactions have only begun to demonstrate the versatility of this chemistry. Rhodium(I)-catalyzed hydroformylation and silylformylation, venerable reactions that have primarily been associated with organometaUic chemistry, must now be considered important tools for natural product synthesis. The continued development of these methodologies for that purpose may be expected. 

In sharp contrast to the unique pattern for the incorporation of carbon monoxide into the 1,6-diyne 63, aldehyde 77 was obtained as the sole product in the rhodium-catalyzed reaction of 1,6-enyne 76 with a molar equivalent of Me2PhSiH under CO (Scheme 6.15, mode 1) [22]. This result can be explained by the stepwise insertion of the acetylenic and vinylic moieties into the Rh-Si bond, the formyl group being generated by the reductive elimination to afford 77. The fact that a formyl group can be introduced to the ole-finic moiety of 76 under mild conditions should be stressed, since enoxysilanes are isolated in the rhodium-catalyzed silylformylation of simple alkenes under forcing conditions. The 1,6-enyne 76 is used as a typical model for Pauson-Khand reactions (Scheme 6.15, mode 2) [23], whereas formation of the corresponding product was completely suppressed in the presence of a hydrosilane. The selective formation of 79 in the absence of CO (Scheme 6.15, mode 3) supports the stepwise insertion of the acetylenic and olefmic moieties in the same molecules into the Rh-Si bond. 

Suisse and co-workers have studied the asymmetric cyclization/silylformylation of enynes employing catalytic mixtures of a rhodium(i) carbonyl complex and a chiral, non-racemic phosphine ligand. Unfortunately, only modest enantioselectivities were realized.For example, reaction of diethyl allylpropargylmalonate with dimethylphenyl-silane (1.2 equiv.) catalyzed by a 1 1 mixture of Rh(acac)(GO)2 and (i )-BINAP in toluene at 70 °G for 15 h under GO (20 bar) led to 90% conversion to form a 15 1 mixture of cyclization/silylformylation product 67 and cyclization/ hydrosilylation product 68. Aldehyde 67 was formed with 27% ee (Equation (46)). 

In sharp contrast to silylformylation of alkynes, specific combination [Rh(GOD)Gl]2/THF of catalyst precursor and solvent is quite important for selective silylformylation of aldehydes. Go-use of A-methylpyrazole is crucial to perform silylformylation of epoxides ( [Rh(GO)2Gl]/GH2Cl2 " and oxetanes [Rh(GO)2Gl]2/toluene. ... 

In addition to alkynes, aldehydes can undergo silylformylation (Equation (27)). Although this reaction pattern was previously carried out with cobalt catalysts, the most important merit in the use of [Rh(cod)Gl]2 or [Rh(GO)2Gl]2 is that the reaction proceeds under far milder conditions. Since such mild conditions make it possible to discriminate starting aldehydes 121 from resultant sterically demanding a-silyloxyaldehydes 122, adjustment of molar ratios of the starting substrates is unnecessary for isolation of product aldehydes. ... 

Choice of THF as the solvent, Me2PhSiH as the hydrosilane, and operation under anhydrous conditions are critical for selective silylformylation of 121 to give 122, whereas these regulations are not necessary in the silylformylation of alkynes. Similar silylformylation is applied to 2-(iV-methylpyrrolidyl)aldehyde (60%), 2-furylaldehyde (90%), 2-thiophenecarboxaldehyde (72%), 2,6-dimethyl-5-heptenal (60%), butanal (60%), 2-methylpropanal (75%), ferrocenecar-boxaldehyde (88%), and phenylacetaldehyde (80%) ... 

Murai and co-workers reported the silylformylation of aliphatic aldehydes in 1979.116 In this version of the transition metal-catalyzed reaction of HSiR3 and CO with various substrates, a formyl moiety is always present in the final product of the reaction. Murai utilized the Co2(CO)8 complex with a triphenylphosphine cocatalyst to catalytically form a-siloxy aldehydes from aliphatic aldehydes. An excess of reactant aldehyde is required to obtain the formyl products if silane is in excess, l,2-bis(siloxy)olefins are produced.117... 

More recently, Wright reported the [RhCl(COD)]2-catalyzed silylformylation of aldehydes, with high yields of the a-siloxy aldehydes under mild conditions [Eq. (44)].118... 

Ring-opening silylformylation has been observed by Murai and coworkers in reactions of cyclic ethers. When the cobalt complex Co2(CO)8 is used as the catalyst in reactions of epoxides, an excess of substrate is required to prevent further reaction of the product siloxy aldehyde.1192 Further investigation led to the discovery of [RhCl(CO)2]2/l-methyl-pyrazole as an effective catalyst combination for the reaction of oxi-ranes119b and oxetanes.J19c For example, oxetane undergoes silylformylation to give 4-(dimethylphenylsiloxy)butanal in 81% yield [Eq. (45)]. 

Two studies of an intramolecular variation of the silylformylation reaction have been reported. In a series of substrates having the acetylene and the hydrosilane as part of the same molecule, silylformylation proceeds intramolecularly with high regio- and stereoselectivity to yield the exocyclic aldehydes in high yields [Eq. (49)].124... 

Although the silylformylation of aldehydes is catalyzed by [Rh(COD)Cl]2 or [Rh(CO)2Cl]2, no secondary silylformylation of /i-silylenals (316-318) takes place, probably due to the electronic nature of the aldehyde functionality conjugated to olefin moiety (vide supra). Direct comparison of the reactivity of acetylene and aldehyde functionalities is performed using alkynals328. The reactions of 5-hexyn-l-al, 6-heptyn-l-al and 7-octyn-l-al with different hydrosilanes catalyzed by Rh or Rh—Co complexes at... 

Arene)tricarbonylchromiums in cycloadditions, 5, 243 in higher-order cycloadditions, 5, 244 in silsesquioxanes, 5, 252 Aromatic acetylenes, silylformylation, 11, 477 Aromatic aldehydes, diastereoselective coupling reactions, 11,44... 

Hydrosilane HSiR.3 behaves similar to H2 toward transition metal complexes in some cases. When HSiR.3 is used instead of hydrogen in hydroformylation, two reactions are expected. One is a hydrocarbonylation-type reaction, by which formation of the silyl enol ethers 62 via the acylmetal intermediate 61, and the acylsilanes 64 via the acyl complex 63, are expected in practice both reactions are observed. The other possibility is silylformylation to form 65, which is unknown, even though silylformylation of alkynes is known. When Co2(CO)8 is used, the silyl enol ether of aldehyde 66 is obtained [36], However, the silyl enol ether 67 of acylsilane 68 is obtained when an Ir complex is used, and converted to the acylsilane 68 by hydrolysis [37],... 

When hydrosilane is used instead of hydrogen in the Rh-catalysed carbonylation of alkynes, the silylformylation of alkynes occurs to give the / -silyl-a,/ -unsaturated aldehydes 71 [38,39]. Oxidative addition of silane to Rh generates the silylrhodium hydride 69. It should be noticed that insertion of alkyne to the Rh-SiR.3 bond, but not... 

Silylcarbonylation is a known term describing formally the silicon version of hydroformylation (cf. Section 2.1.1) discovered by Collenille [147] and later developed by Murai and co-workers, in which hydrogen is replaced by trialkylsilane, eq. (10) [148]. The silylformylation of alkenes is catalyzed by Co2(CO)g [148], [RhCl(CO)2]2 [149], RhCl(PPh3)3 [150], Ru3(CO)i2, and HRujfCO),- [151] to give silyl enol ethers of the homologous aldehydes as the sole products. 

The silylformylation of oxygen-containing compounds such as aldehydes and cyclic ethers in the presence of Co2(CO)g and [Rh(COD)Cl]2 affords siloxy derivatives according to eqs. (11) and (12) [148, 152]. 

Highly functionalized olefins are easily accessible via silyformylation of alkynes. When coupled to other reaction systems, silylformylation reactions become even more powerful. Eilbracht et al. demonstrated that stabilized phosphorous ylides 74 could be trapped by P-silylated a-P-unsaturated aldehydes formed via silylformylation of alkynes in a one-pot synthesis. The tandem reaction proceeds with high yields for both alipathic and aromatic terminal alkynes. Protected propargyl alcohols also showed good reactivity however, propargyl amines react with low selectivity. The reaction shown below is the best-afforded result for this process. ... 

Silylformylation is a powerful synthetic tool for the synthesis of substituted-formylvinylsilanes. In 2001, the des3nnmetrization of dimethylsiloxyalkadiynes 80 to afford 81 as well as a novel sequential double silylformylation affording an unsaturated cyclooxasilanes (82) was reported. The product afforded by single desymmetrization reaction can subsequently be converted to 1,3,5-triols by way of Tamao oxidation, with subsequent reduction of the resultant keto-aldehyde. Additionally, it was found that use of phenyldimefliylhydrosilane decreased the reaction time, whereas use of bulkier hydrosilanes, e.g., /-butyldimethylsilane required both increased time and temperature. ... 

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