Ketones, a-silyl

Diazaphospholes are known to undergo facile 1,3-dipolar cycloaddditions with a variety of dipoles [2, 4, 7, 98], During recent years, some interesting [2+3] cycloaddition reactions have been reported. 2-Acyl-[l,2,3]diazaphospholes 6 were reported to undergo [2+3] cycloaddition with diazocumulene 92, the minor equilibrium isomer of a-diazo-a-silyl ketones 91, to form a bicyclic cycloadduct 93 (Scheme 29). Thermolysis of the cycloadduct results in the formation of tricyclic phosphorus heterocycle 94, which can be explained due to the possibility of two parallel reactions of cycloadduct. On the one hand, extrusion of molecular nitrogen from 93... 

Retro-Brook rearrangement of the [l,3]-variant will readily take place in sp and sp carbanion systems. Kuwajima and Takeda and Corey and Rticker have developed the [l,3]-retro-Brook rearrangement of silyl enol ether anions which provide a-silyl ketones (equation 100 and 101). 

ElectrophiHc substitutions with carbon and hetero electrophiles a to the carbonyl group of aldehydes and ketones are among the most important synthetic operations. Such regio-, diastereo-, and enantioselective substitutions can be carried out efficiently with the SAMP/RAMP hydrazone methodology [3]. For cases where virtually complete asymmetric inductions could not be attained, an alternative approach based on a-silylated ketones 2 was developed [4]. They can be prepared easily from ketones 1 in high enantiomeric purity (ee > 98%) by asymmetric carbon silylation employing the SAMP/RAMP hydrazone method (Fig. 1.1.1). After the introduction of various electrophiles via classical enolate chemistry with excellent asymmetric inductions, the desired product ketones 3... 

Although efficient organocatalytic methods for the electrophilic a-fluorination of aldehydes and ketones have recently been developed [7], high enantiomeric excesses can only be reached with aldehydes so far. The asymmetric inductions in the case of ketone fluorinations have remained low ee < 36%) [7a]. Thus, the a-silyl ketone-controlled stoichiometric asymmetric synthesis of a-fluoroketones 10 (Scheme 1.1.1) still constitutes a practical method. 

Silyl enol ethers Trimethylsilyl enol ethers can be obtained from a-silyl ketones by thermal rearrangement or by catalysis with HRh(CO)[P(C6H5)3]3, (CH3)3SiOTf, or ISi(CH3)3. The first two methods are (E)-selective in the case of unsymmetrical ketones, whereas the latter two are (Z)-selective. 

Rearrangement of (a-methyldiphenylsilyl)alkyl ketones.1 These a-silyl ketones rearrange thermally to a mixture of (Z)- and (E)-enol silyl ethers. However, rearrangement in acetonitrile results in only the (Z)-enol silyl ethers (>99 1). These enol silyl ethers are useful precursors to (Z)-lithium enolates. 

A /3-hydroxysilane, like the one shown in Figure 4.38 (top, left), can be prepared stereo-selectively (e.g., via the Cram-selective reduction of an a-silylated ketone according to the reactions in Figure 8.9 or via the Cram-selective addition of organometallic compounds to a-silylated aldehydes similar to what is shown in Table 8.3). These compounds undergo a stereoselective anft -elimination in the presence of add and a stereoselective syn-elimination in the presence of a base (Figure 4.38). Both reactions are referred to as Peterson olefination. The stereochemical flexibility of the Peterson elimination is unmatched by any other HetVHet2 elimination discussed in this section. 

Simpkins and coworkers reported the use of chiral bases in the enantioselective generation of bridgehead enolates (Scheme 36)76. Initial studies revealed that external quench protocols were ineffective in trapping the carbanion. Addition of a mixture containing chiral base (R,R) 3 and LiCl to a solution of ketone 55 and TMSC1 at —105 °C gave mono (—)-a-silylated ketone 56 in 76% yield and >96% ee. 

The corresponding saturated ketone gave, under similar conditions, (—)-a-silylated ketone in 53% yield and >92% ee. A drawback of this reaction is the incompatibility of in situ quench conditions with most electrophiles. 

Note 11). The residual activated magnesium is rinsed once with 200 mL of dry diethyl ether, and the supernatant layer is transferred via cannula to the copper bromide-dimethyl sulfide slurry (Note 12). The reaction mixture is slowly warmed to -10°C, and then 16.78 g (17.42 mL, 125 mmol) of hexanoyl chloride is added dropwise via syringe after which the reaction mixture is warmed to room temperature. After stirring for 3 hr, the reaction mixture is filtered through a 75-g layer of Celite 545 (Note 13) and the filter cake rinsed with three 100-mL portions of diethyl ether. Concentration of the filtrate under reduced pressure yields the a-silyl ketone which is utilized without further purification (Note 14). 

The Celite used is NOT the acid-washed reagent. Acid-washed Celite will cause some desilylation of the a-silyl ketone intermediate. 

The a-silyl ketone may be stored overnight either under vacuum or under argon at -20°C. 

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... 

The procedure shown here describes the preparation of a-silyl ketones from aldehydes and acyl chlorides. The a-silyl ketones undergo Cram addition of various nucleophiles to produce diastereoselectively p-hydroxysilanes. These compounds are then subjected directly to elimination in situ under basic or acidic conditions to produce the corresponding alkenes. 

Aldol coupling of chiral acetals. The acetals (2) prepared from an aldehyde and (2R,4R)-pentanediol react with a-silyl ketones orenol silyl ethers in the presence of TiCI, to form aldol ethers 3 and 4 with high diastereoselectivity (>95 5). Removal of the chiral auxiliary usually results in decomposition of the aldol, but can be effected after reduction... 

OL-Silyl ketones,l Silyl enol ethers with sterically hindered silyl groups rearrange to a-silyl ketones in the presence of /i-BuLi (2 equiv.) and KO-f-Bu (2.5 equiv.). Tri-methylsilyl ethers do not undergo this rearrangement, but triisopropylsilyl (TIPS) and diisopropylmethylsilyl (DIMS) ethers do if they contain an allylic a-proton. The silyl group rearranges preferentially to the less hindered terminus of the intermediate allyl anion. The rearrangement is less useful with acyclic substrates because of side reactions. 

Asymmetric a-amination of enolates has also been described. For example, treatment of a-silyl ketone 109 with LDA followed by addition of oxaziridine 65a gave the A -BOC-amino ketone 110 in 29% yield and 88% de <1998TA3709>. Asymmetric amination of the prochiral enolate of 111 with chiral nonracemic oxaziridine 112 afforded amino ester 113 in 51% yield and 21% de <2001TA535>. 

The aggregation pheromone of the rice and maize weevil was synthesized by aldol reaction of an enantiomerically pure a-silyl ketone, obtained by the SAMP/RAMP hydrazone method,with various aldehydes (eq 8). ... 

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