Acyl silane

In a cross-coupling benzoin condensation of two different aldehydes, usually a mixture of products is obtained, with the ratio being determined by the relative stabilities of the four possible coupling products under thermodynamic control. If, however, an acyl silane, e.g. 5, is used as the donor component, the a-silyloxy-ketone 6 is obtained as a single product " ... 

Two other examples of microwave-assisted Paal-Knorr reactions were reported in 2004, describing the synthesis of a larger set of pyrroles with different substituents around the ring. The methods differ mainly in the syntheses employed to produce the 1,4 dicarbonyl compounds required for the cyclization. A variation of the Stetter reaction between an acyl silane and dif-... 

Alternative methods to access the same Breslow intermediate using NHCs utilising acyl silanes [3] or a-keto-acids have been developed [4], although these processes have not been utilised in asymmetric transformations to date. 

Enones and enoates undergo 1,2-reduction [115, 191]. Lipshutz et al. reported the effective protection of carbonyl functions by the triisopropylsilyl acyl silane group (TIPS), which allowed the selective conversion of alkenes or alkynes to the corresponding zirconocene complexes [24]. The aldehyde could subsequently be regenerated by desilylation with TBAF [186]. 

Compared to the cyclic ketones, the coupling of aliphatic aldehydes to prepare 3-substituted indoles was less successful, except for phenyl acetaldehyde, which afforded 3-phenyl indole 83 in 76% yield (Scheme 4.22). The lack of imine formation or the instability of the aliphatic aldehyde towards the reaction conditions may be responsible for the inefficiency of these reactions. Therefore, a suitable aldehyde equivalent was considered. With the facile removal of a 2-trialkylsilyl group from an indole, an acyl silane was tested as a means of preparing 3-substituted indoles. Indeed, coupling of acetyl trimethylsilane with the iodoaniline 24 gave a 2 1 mixture of 2-TMS-indole 84 and indole (85) in a combined 64% yield. Evidently, the reaction conditions did lead to some desilylation. Regardless, the silyl group of 84 was quantitatively removed upon treatment with HC1 to afford indole (85). 

The addition of carbonyl compounds towards lithiated 1-siloxy-substituted allenes does not proceed in the manner described above for alkoxyallenes. Tius and co-work-ers found that treatment of 1-siloxy-substituted allene 67 with tert-butyllithium and subsequent addition of aldehydes or ketones led to the formation of ,/i-unsaturated acyl silanes 70 (Scheme 8.19) [66]. This simple and convenient method starts with the usual lithiation of allene 67 at C-l but is followed by a migration of the silyl group from oxygen to C-l, thus forming the lithium enolate 69, which finally adds to the carbonyl species. Transmetalation of the lithiated intermediate 69 to the corresponding zinc enolate provided better access to acylsilanes derived from enolizable aldehydes. For reactions of 69 with ketones, transmetalation to a magnesium species seems to afford optimal results. 

With thione 113, l-(trimethylsilyl)-l-(l -ethoxy)ethoxypropadiene affords afi-wa-saturated acyl silane 115 [56],... 

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. 

The benzoin reaction typically consists of the homocoupling of two aldehydes, which results in the formation of inherently dimeric compounds, therefore limiting the synthetic utility. The aoss-benzoin reaction has the potential to produce four products, two homocoupled adducts and two cross-benzoin products. Several strategies have been employed to develop a selective cross-benzoin reaction, including the use of donor-acceptor aldehydes, acyl silanes, acyl imines, as well as intramolecular reactions. 

In an effort to circumvent a homodimerization event acyl silanes have been used to promote a cross-benzoin reaction. Initial reports by Johnson and co-workers employed potassium cyanide to catalyze the regiospecific cross silyl benzoin reaction to afford a single regioisomer in good yield (Eq. 2) [45 7]. 

The proposed mechanism is as follows initial cyanation of the acyl silane followed by a [1,2]-Brook rearrangement yields acyl anion equivalent XIV (Scheme 4). Subsequent attack by the acyl anion equivalent XV to the aldehyde leads to... 

Shortly after publishing the racemic cross silyl benzoin reaction, Johnson and co-workers reported an enantioselective variant ntilizing metallophosphite catalysis [48]. The lithiophosphite adds to the acyl silane and proceeds throngh the remain-... 

Scheme 4 Proposed mechanism for the acyl silane cross-benzoin reaction...

Table 3 Acyl Silane cross-benzoin reaction catalyzed by lithiophosphites...

Taking advantage of the acyl silane and imine methodologies, Scheidt and co-workers illustrated the use of acyl silanes 61 and iV-diarylphosphinoylimines 62 to form a-amino ketones 63 (Eq. 4) [55], Utilizing thiazolium pre-catalyst 64, a variety of acyl silanes, both alkyl and aryl, can be coupled efficiently. The reaction conditions are tolerant of various aryl substitutions, providing high yields. 

In a related process, Johnson and co-workers have developed an asymmetric metallophosphite-catalyzed intermolecular Stetter-hke reaction employing acyl silanes [81, 82], Acyl silanes are effective aldehyde surrogates which are capable of forming an acyl anion equivalent after a [l,2]-Brook rearrangement. The authors have taken advantage of this concept to induce the catalytic enantioselective synthesis of 1,4-dicarbonyls 118 in 89-97% ee and good chemical yields for a,p-unsaturated amides (Table 11). Enantioselectivities may be enhanced by recrystallization. 

Scheldt and co-workers have shown that acyl silanes behave analogously to aldehydes in the Stetter manifold, ultimately forming 1,4-dicarbonyls 120 in yields up to 75% [83, 84], A range of acyl silanes are compatible in this reaction Eq. 11. 

Pyrrole synthesis has been shown to be more general than furan (Table 12). Scheldt and co-workers have subsequently shown that acyl silanes may again be used as aldehyde surrogates in this protocol [83, 87]. 

Other magnesium allenyl enolates, such as 22, obtained by transmetallation of the lithium species have been used successfully in the preparation of a,-unsaturated acyl silanes (equation 28). ... 

The very different reactivity toward allylation of a,P-unsaturated esters and acyl-silanes [132] is due to stabilization of the allyl cation intermediates by the alkoxy group in the former class of substances, in contrast to those derived from acylsilanes which are expected to be less stable than 3-monooxyallyl cations. In the 1,1-dioxy substituted cations two donor atoms are bonded to the acceptor site, but in the 1-oxy-3 -silyl congeners a rf,a-antagonism (captodative) exists. 

The second route involves the palladium catalyzed coupling of iodoaniline 51 with the acyl silane 54 in the presence of DABCO to give the 2-trimethylsilyl indole 55. The acyl silane 54 was prepared by alkylation of 1,3-dithianyl-trimethylsilane with (3-bromopropyl)-dimethylamine to give 56, followed by removal of the dithioacetal with mercuric oxide and mercuric chloride. Finally, desilylation of 55 in aqueous HCl and methanol afforded rizatriptan (4). 

Scheme 20. Synthesis of rizatriptan (4) via Pd-catalyzed coupling of iodoaniline 51 and acyl silane 54.

Anodic oxidation provides also an efficient way for the regeneration of a carbonyl group from its dithioacetal derivative. This method proved to be useful in dethioacetalization of oses [51] and of acyl silanes [52]. 

Acyl silanes by anodic oxidation of2-alkyl-2-trialkylsilyl-l,3-dithianes... 

Preparation from enol ethers of acyl silanes. 1623... 

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