Acylation silanes, ketones from

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. 

In an interesting transformation, reaction of benzoyl trimethylsilane with lithium enolates derived from various methyl ketones gives rise to 1,2-cyclopropanediols, predominantly with the cis configuration, in good yields (Scheme 77). The reaction, which proceeds through addition, Brook rearrangement and cyclization, is also successful with a,/l-unsaturated acyl silanes vide infra, Section IV.D)187. 

Cycloaddition reactions of acyl silanes appear to be rare, but Brook has shown that a-silyloxy bis(trimethylsilyl)silenes (52), generated photochemically from acyl tris(trimethylsilyl)silanes (vide infra, Section IV.A.4), undergo [2 + 2] and [4 + 2] cycloaddition reactions with ketones, and [4 + 2] cycloaddition reactions with less bulky acyl silanes, as illustrated in Scheme 8717,24 26 72 73,201. They do not, however, react with their parent acyl tris(trimethylsilyl)silanes. 

There are two approaches to lithium derivatives of aldehydes, though neither starts from the aldehydes themselves. Carbonylation of primary alkyl-lithiums gives an intermediate,4 probably 8, that adds to aldehydes or ketones, e.g. 9, to give hydroxyketones 10 and can be silylated to give the acyl silane 11. 

Alternatively the Me3Si group may in turn be removed from the acyl silanes 11,12 or 14 with CsF to give possibly the acyl anion itself, or at any rate a species which adds to aldehydes and ketones in the same way,5 and even does Michael reactions to give e.g. 15. 

The concept of silyl enol ether synthesis via / -elimination from a Brook rearrangement-derived carbanion also appeared in Wicha s studies on additions of 1-phenyl-l//-tetrazol-5-yl (PT) sulfonyl anions to acyl silanes. When PT sulfone 34 was deprotonated in the presence of acyl(triphenyl)silane, ketone 36 was isolated in good yield after hydrolysis of the silyl enol ether intermediate 35. The mechanism involved addition of the... 

The NMR signals of carbonyl groups in acyl silanes are dramatically shifted down-field in comparison to the analogous ketones (Table 3) . The effect ranges from ca 25 to 100 ppm, and is approximately additive. 

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

The acid or base elimination of a diastereoisomerically pure p-hydroxysilane, 1, (the Peterson olefination reaction4) provides one of the very best methods for the stereoselective formation of alkenes. Either the E- or Z-isomer may be prepared with excellent geometric selectivity from a single precursor (Scheme 1). The widespread use of the Peterson olefination reaction in synthesis has been limited, however, by the fact that there are few experimentally simple methods available for the formation of diastereoisomerically pure p-hydroxysilanes.56 One reliable route is the Cram controlled addition of nucleophiles to a-silyl ketones,6 but such an approach is complicated by difficulties in the preparation of (a-silylalkyl)lithium species or the corresponding Grignard reagents. These difficulties have been resolved by the development of a simple method for the preparation and reductive acylation of (a-chloroalkyl)silanes.7... 

Three types of products have been observed in intermolecular acylations of homoallylic silanes, the major one being cyclopropylmethyl ketones, along with minor amounts of 3-butenyl ketones and -chlo-ro ketones. It is likely that all derive from the carbenium ion formed by acylation of the double bond, which then undergoes cyclodesilylation or hydride transfer followed by 3-elimination (Scheme 14). The former leads to the cyclopropane, which can ring open to give the chloro products. The latter pathway gives the butenyl ketone, and is supported by location of substituent positions on methylated substrates. However, the direct acylation of the carbon-silicon bond should not necessarily be excluded in consideration of more general cases. Titanium tetrachloride seems the preferred catalyst in these cyclodesilyl-ations, and low temperatures minimize the formation of the chloro by-products. Intramolecular versions... 

Ryu, Sonoda and coworkers reported that tris(trimethylsilyl)silane is a useful mediator for a three-component coupling reaction [45]. Table 4 summarizes examples of radical carbonylations mediated by (TMS)3SiH. The first example shows a three-component coupling reaction in which hexyl iodide, CO, and acrylonitrile combine to form a P-cymo ketone. The CO addition step is in competition with the addition to the alkene and the hydrogen abstraction from radical mediator. Thus, it is anticipated that a set of less efficient hydrogen donors, such as (TMS)3SiH, and the use of a smaller excess amount of an alkene is most favorable. Indeed, the reaction can be carried out at only 20 30 atm of CO pressure, substantially below the 80-90 atm which is used for carbonylative acyl radical reactions which are mediated by tin hydride, and a nearly stoichiometric amount (1.2 equiv) of acrylonitrile is sufficient. Some other examples, which include vinyl radical carbonylation, are also shown in Table 4. 

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