Silylformylations under

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. 

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. 

We have explored two types of carbon-carbon bond forming reactions operated under almost neutral conditions. Both reactions are initiated by the formation of an H-Rh-Si species through oxidative addition of a hydrosilane to a low-valence rhodium complex. Aldol-type three-component couphngs are followed by the insertion of an a,yS-unsatu-rated carbonyl compound into a Rh-H bond, whereas silylformylation is accomplished by the insertion of an acetylenic moiety into a Rh-Si bond. 

In the first rhodium-catalyzed carbonylative silylcarbocyclization (CO-SiCaC), which was reported in 1992 [12, 13], silylcyclopentenone 9 was isolated as a minor product in the silylformylation of 1-hexyne 8 (Scheme 7.4). Under optimized conditions using Et3SiH and ( BuNC)4RhCo(CO)4 as the catalyst at 60°C, 9 is formed in 54% yield [13]. A possible mechanism proposed for this intermolecular CO-SiCaC is shown in Scheme 7.4 [13]. In this mechanism, the formation of 9 is proposed to proceed via in-... 

Matsuda independently developed an alternative procedure for the cyclization/silylformylation of enynes that did not require the use of phosphite ligand, and which was effective with low catalyst loading. As an example, reaction of a benzene solution of acetal 65 (0.1 M) and dimethylphenylsilane catalyzed by Rh(acac)(GO)2 (0.005 mol%) under GO (20 bar) at 90 °G for 14 h formed silylated alkylidene carboxaldehyde 66 in 89% yield (Equation (44)). 

Ghung has developed an effective protoeol for the cyclization/silylformylation of 1,6-enynes catalyzed by cobalt/ rhodium nanoparticles (Go2/Rh2). For example, reaction of dimethyl allylpropargylmalonate and triethylsilane catalyzed by Go2/Rh2 in dioxane at 105 °G under GO formed the corresponding silylated cyclopentane... 

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)). 

It should be emphasized that the formyl group remained intact in major product 3 despite the reaction under forcing conditions. This is the first example of silylformylation in which a trialkylsilyl group and a formyl group are simultaneously connected to acetylenic carbons to form 1 in a one-pot reaction. Based on this breakthrough, the Matsuda group " published refined results and coined the word silylformylation . The reaction has since been applied to a variety of substrates as described in the following sections. 

Phenylacetylene 13 readily reacts with Me2PhSiH under CO pressure to give 3-dimethylphenylsilyl-2-phenyl-propenal 14a in the presence of a catalytic amount of Rh4(CO)i2 (Equation (2)). When 10-20 atm of CO pressure and 0.1-0.2 mol% of Rh4(GO)i2 are applied, the reaction is completed within 2 h at 100 °G. Silylformylation proceeds smoothly even at room temperature, though the reaction becomes slower (600-700 turnover frequency at room temperature after 17 h). The reaction does proceed in the absence of Et3N, but its presence improves yield and (Z)-selectivity of product 14a. ... 

A bulky substituent appears to suppress yield of the silylformylation product under the equal conditions. Pr 3SiH is recovered. 

Rhodium-catalyzed silylformylation proceeds smoothly in branched 1-alkynes at 25 °C as shown in Table 3. The stereochemistry at the chiral carbon involved in alkynes is retained intact under the silylformylation conditions. (A)-28, (rhodium particles co-condensed with mesitylene. 3-Trimethylsilyl-l-propyne 40 reacts similarly to give 41 (Equation (7)). " / //-Butylacetylene does not work as a substrate for the silylformylation because of the bulky tert-huty group on the i/>-carbon. In contrast to /< r/-butylacetylene, trimethylsilylacetylene 42 gives 43 in a fair yield (Equation (8)). ... 

Ethene and 1-hexene do not react with hydrosilane under GO pressure in the presence of an Rh catalyst. Any product is obtained under the conditions similar to the reaction of 1-alkynes. Thus, the alkynyl moiety in pent-l-ene-4-yne 48, 4-oxahept-l-en-6-yne 50, and 4-oxa-2-methylhept-l-en-6-yne 52 is solely silylformylated to give 49, 51, and 53, respectively (Equations (12)-(14)). 

In the reaction of parent propargyl amine, unidentified intractable materials are formed even under relatively mild conditions. However, selective silylformylation at the alkynyl moiety proceeds by reducing the nucleophilicity of the amino group as tosylamide or carbamate (Table 5). ... 

Although silylformylation of 3-butyn-I-ol 84 gives normal product 85 preferentially in the absence of EtsN, an appreciable amount (38%) of 7-lactone 86 is formed concomitantly." Protection of the hydroxy group in 84 leads to selective silylformylation of the acetylenic moiety as shown in Scheme 3. Hydrolysis of the silyl ether in 88 gives 85 as a single product. 4-Pentyn-I-ol 89 reacts with Mc2PhSiH under CO pressure to give a mixture of silylformylation product 90 (20%) and (5-lactone 91 (38%) after a short reaction time (0.5 h) (Equation (16)). The unusual lactone formation is not observed in the reaction of 5-hexyn-l-ol 92 in the presence of EtsN (Equation (17)). ... 

In a manner similar to silylformylation, germylformylation of 1-alkynes catalyzed by 12 proceeds with Bu aGeH under CO pressure (20 atm). However, it is difficult to completely suppress hydrogermylation of 1-alkynes as the side-reaction. ... 

On the other hand, alkenal 14a is selectively formed with recovery of Rh4(GO)i2 under CO pressure (20 atm) in a stoichiometric reaction mole ratio = Rh4(GO)i2 13 Me2PhSiH = 1 4 4 as well as a catalytic reaction. When 13 and Me2PhSiH are mixed at once in a GDGI3 solution of Rh4(GO)i2 under CO atmosphere, 14a is smoothly formed as a major product with concomitant formation of small amounts of 15 and Me2PhSiOH. In the case that 13 and Me2PhSiH are added separately, it is critical to add 13 to a solution of Me2PhSiH and Rh4(CO)i2 for the production of 14a. Reverse addition results in hydrosilylation of 13 only. Similar results are observed in the silylformylation catalyzed by Rh2(pfb)4. ... 

In contrast to the results of Equation (25), Scheme 4, and Scheme 5, four rhodium complexes, Rh4(CO)i2, 7a, 7b, and 11a, uniformly interact with a stoichiometric mixture of Me2PhSiH and phenylacetylene 13 to give 14a within 1 h under GO pressure. The respective starting complex remains intact after completion of silylformylation (Scheme 8). The results in Equation (26) and the behavior of 7b in Scheme 8 suggest strongly that the alkyne moiety in 7 is not incorporated directly as a product of silylformylation. 

All the starting compounds in Scheme 8 have a sufficient potential for both catalytic and stoichiometric silylformylation, when Me2PhSiH and 1-alkyne are present in a reaction vessel at the same time. Stable mononuclear complex, RhH(GO)(PPh3)3, is far inferior in catalyst efficiency at 25 °G, though the efficiency is improved under practical operation at 100 °C (Table 6). Though 7 and 11 are derived from Rh4(GO)i2 under controlled conditions and work as an active catalyst of silylformylation, their position in the catalytic cycle is still a precursor of truly active species, because it takes a far longer induction period for activation than that for silylformylation. 

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%) ... 

Selectivity for the cyclopentenone formation is improved by an intramolecular version. For example, 1,6-hepta-diyne (256, X = CH2) reacts in benzene with 2molarequiv. of Bu Me2SiH to give two bicyclo[3.3.0]octenones, 257 and 258, in 14% and 63% yield, respectively, at 95 °G under GO (20 atm) pressure.When benzene is replaced by acetonitrile, 258 becomes a sole product (60% yield). On the other hand, the reaction at 25 °G gives normal silylformylation product 259 as a major component (59%) with the concomitant formation of 258 (20%) (Scheme 12). ... 

When this reaction is carried out under 1 atm of nitrogen or GO atmosphere, a cyclopentane 276 is formed selectively in a minute at 25 °G (Scheme 13, mode 2). Although the Pauson-Khand reaction of 1,6-enyne 273 (Scheme 13, mode 3) gives 21H, this transformation is completely suppressed under the conditions of mode 1. Even simple alkyne silylformylation product 277 is not detected at all. This contrasts sharply to the silylformylation of l-penten-4-yne 48 carried out under similar conditions (Equation (12)). These results can be explained by a pathway similar to the reaction of 1,6-diynes (i) stepwise insertion of the acetylenic and olefmic moieties into the Rh-Si bond in this order, and (ii) subsequent interaction of GO and Mc2PhSiH with the resultant intermediate to give 275. The... 

Thus, the formation of 2-silylmethylalkenals 288 from 287 can be explained by the intervention of a silylformylation product 295 and its consecutive reaction with another molecule of R3SiH under CO pressure as shown in Scheme 15. ... 

This mechanism suggests that 288 may be constructed by a similar sequential reaction starting from propargylic alcohols, 70. Under the standard conditions, 70 is silylformylated to give 71, which upon treatment with... 

Silylformylation of 1-alkynes proceeds smoothly even in the presence of a base or a protic reagent. This feature makes it possible to design a cascade-type condensation using the resultant 3-silylalkenals as a component in one-pot operation during the silylformylation. Aza-1,3-dienes 303 are formed with sufficient selectivity by the reaction of 1-alkyne, a hydrosilane, primary amine, and GO under the silylformylation conditions (Equation (52)). ... 

A novel hydrazepine formation is observed in the iridium-catalyzed reaction of alkynyl hydrazone 304 with Bu Me2SiH in excess under slightly forcing conditions (Equation (53))/ The transformation leading to 305 can be explained by continuous interaction of Bu MceSiH with a silylformylation product of 304 under the reaction conditions/ ... 

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... 

Ojima and co-workers have also extensively studied the catalytic silylformylation of alkynes, employing a number of rhodium and rhodium-cobalt mixed metal complexes.122 The reaction of 1-hexyne with hydrosilanes under either ambient pressure or 10 atm of CO is catalyzed by a variety of metal complexes to yield (Z)-l-silyl-2-formyl-l-hexene, 1, and/or ( )-l-silyl-l-hexene, 2 [Eq. (48)].122a>c... 

The outcome of the reaction is affected by hydrosilane, CO pressure, and choice of catalyst. The hydrosilane substituents influence the selectivity of the reaction, i.e., relative ratio of silylformylation to hydrosilylation. For example, silanes with phenyl substituents, such as Me2PhSiH, Ph2MeSiH, and Ph3SiH, lead exclusively to silylformylation products, but at least 80% of the product derived from trimethoxysilane is due to hydrosilylation. Trialkylsilanes generally give 40 60 mixtures of hydrosilylation and silylformylation products. The carbon monoxide pressure under which the reaction... 

A surprising variation on the silylformylation reaction has been reported by Zhou and Alper. A zwitterionic rhodium(I) complex, (l,5-COD)Rh+(Tj6-PhBPh3), catalyzes the silylformylation of alkynes under normal reaction conditions. However, if H2 is added to the system, the reaction may proceed to yield silylalkenals of a different structure. Interestingly, although the H2 must play a key role in the reaction, it is not incorporated in the product. At this time, the mechanistic role of the hydrogen remains unclear. The authors term this reaction a silylhydroformylation [Eq. (51)].126... 

This appears to be the first report of the addition of H2 to the silylformyla-tion reaction mixture. Good yields are obtained when Et3SiH or PhjSiH is used in the reaction of 1-hexyne or 4-phenyl-l-butyne. Although a variety of functionally substitued terminal alkynes have been studied, most lead only to the silylformylation product and do not appear to be affected by the presence of H2 in the system. Other rhodium catalysts investigated, such as [Rh(COD)(dppb)]+BPh4 and Rh6(CO)16, catalyze the silylformylation reaction even under H2 pressure and do not lead to any of the silylhydrofor-mylated products. 

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