Silylformylations

Mesitylene-solvated Rh atoms are valuable catalytic precursors for the selective silylformylation of a wide... 

Using propargyl alcohols and propargylamine derivatives as acetylenic compounds, the silylformylation reaction affords, in the presence of a base, a-silylmethylene-P-lactones, I, and P-lactams, II, respectively (Scheme 3) [13]. 

This tandem intramolecular silylformylation/Sakurai reaction has successfully been applied in a formal total synthesis of mycoticin A [75]. The scope and utility of these reactions was expanded to (Z)- and (E)-crotyl groups leading to the stereospecific incorporation of both anti and syn propionate units into the growing polyol chain (Scheme 21) [76]. 

Scheme 21 Synthesis of polyol fragments via silylformylation/Sakurai reaction...

Scheme 22 Application of the silylformylation/Sakurai reaction in the synthesis of poly-ketides...

When substituted silanes are used instead of hydrogen, the process is referred to as silylformylation or silylcarbonylation. Only rhodium complexes catalyze the transformation of unsaturated compounds to silylaldehydes via the silylformylation reaction. Iridium complexes also are able to catalyze the simultaneous incorporation of substituted silanes and CO into unsaturated compounds, although during the reaction other types of product are formed. In the presence of [ IrCl(C03) ] and [Ir4(CO)i2]) the alkenes react with trisubstituted silanes and CO to give enol silyl ethers of acyl silanes [58] according to Scheme 14.10. 

Stereoselective Rhodium(l)-Catalyzed Hydroformylatlon and Silylformylation Reactions and their Application to Organic Synthesis... 

I 5 Stereoselective Rhodium(l)-Catalyzed Hydroformylation and Silylformylation Reactions... 

I 5 Stereoselective Rhodium (l)-CatalYzed Hydroformyiation and Silylformylation Reactions 5.2.2... 

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. 

Alkenes had been identified as potentially important substrates for silylformylation, but initial attempts using Co2(CO)g as the catalyst produced instead the silyl enol ether... 

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... 

Alkynes are viable substrates for the tandem intramolecular silylformylation/allylsilyla-tion reaction. The 1,5-diastereoselechvity is reversed from that observed with alkene substrates, as the 1,5-anti product predominates (Scheme 5.24) [38]. Synthetic flexibility was demonstrated in that either of two carbon-silicon cleavage procedures may be employed. Protodesilylahon with tetra-n-butylammonium fluoride followed by acetylation (determi-... 

I 5 Stereoselective Rhodium i)-Catatfzed HydroformYlation and SilylformYlation Reactions... 

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 tandem silylformylation/allylsilylation reaction is particularly well suited to the synthesis of skipped polyol motifs such as are found in the oxopolyene macroHdes. The synthesis of protected triol 43 (an intermediate in the mycoticin A formal synthesis described above see Scheme 5.18) relied on an application of this methodology. Thus, homoallylic alcohol 76 was transformed into triol 77 in 55% overall yield and >10 1 diastereoselectivity (Scheme 5.27) [23]. Selective protection of the triol to give 43... 

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. 

A further piece of evidence to elucidate the catalytic pathway of silylformylation was provided by a pair of deuterium-labeled reactions. The results revealed that the scrambling of hydrogen atoms between a hydrosilane and a terminal acetylene is minimal during the reaction and that the hydrogen atom of the formyl group and the vinylic hydrogen are derived from the hydrosilane and the acetylenic proton, respectively (Eq. 8) [15 bj. 

Generally the functional groups in 28 do not interfere in the silylformylation to afford 29 (Tab. 6.3), for example, 28 having hydroxy, p-tosylamino and carbomate... 

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