Silyl nucleophilic activator

In metal-free catalysis enantioselective ring-opening of epoxides according to Scheme 13.27 path B has been achieved both with chiral pyridine N-oxides and with chiral phosphoric amides. These compounds act as nucleophilic activators for tetrachlorosilane. In the work by Fu et al. the meso epoxides 71 were converted into the silylated chlorohydrins 72 in the presence of 5 mol% of the planar chiral pyridine N-oxides 73 (Scheme 13.36) [74]. As shown in Scheme 13.36, good yields... 

The electrophile coordinates to the Lewis acid first producing an activated enone that is attacked by the silylated nucleophile. It is difficult to determine at what stage the trimethylsilyl group moves from its original position and whether it is transferred intramolecularly to the product. In many cases the anion liberated from the Lewis acid (Cl-, RO , Br-) is a good nucleophile for silicon so it is reasonable to assume that there is a free trimethylsilyl species (Me3SiX) that captures the titanium enolate (Chapter 28). 

The ring opening reaction of A-tosylaziridines with certain silylated nucleophiles via a similar activation has been reported recently (Wu et al. 2006). 

The same catalyst is also effective in three-component reactions between aldehydes, amines, and silylated nucleophiles, leading to amino ketone, amino ester, and amino nitrile derivatives, respectively (Eq. 30) [114]. It is reported that 103 can be recovered and that continuous use is possible without any loss of activity. More interestingly, in competitive reaction of aldehyde, aldimine and silyl enolate, the less reactive aldimine reacted exclusively with silyl enolate in the presence of 103. This unique selectivity was explained by the polymer effect [115]. 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

Ueno,M., Hori,C., Suzawa, K. efa/. (2005) Catal3dic activation of silylated nucleophiles using Bu-P4 as a base. European Journal of Organic Chemistry, 1965-1968. 

In contrast, the high Lewis basicity of NHCs also explains their capability to activate silylated nucleophiles by coordination to the silicon atom (Scheme 5.32, Eq. 4), while their Br0nsted basicity allows for activation of alcohols or amines via hydrogen bonding. 

Other synthetic applications of the phosphazene bases include the use of Bu -Pl (37) in the alkylation of adenine in solution or solid phase, and the catalytic esterification of various glycerol derivatives with fatty methyl esters at room temperature. On occasions, the action of the phosphazene bases may promote processes that other proton abstractors do not, such as the observed rearrangement of (43) to the flavone (44) in the presence of (40e) (OBn = benzoyloxy). Patented process, include the purification " and assembly of polyhedral oligomeric silsesquioxane monomers, and the catalytic activation of silylated nucleophiles. ... 

As described by Cordova et al., the strategy of combining transition metal-catalysed nucleophilic activation with chiral amine-catalysed iminium activation allows the enantioselective conjugate silyl addition to a,p-unsaturated aldehydes [115]. The reaction proceeds with good 1,4-selectivity and moderate enantio-selectivity when p,p-disubstituted unsaturated aldehydes are used as substrates, as exemplified in Scheme 77. The silylated products are versatile adducts that can be easily converted to protected 1,3-diols and p-functionalised esters. 

Song et al. have exploited the Lewis base properties of pre-generated N-heterocyclic carbenes to activate silylated nucleophiles. In 2005, these researchers reported the NHC-catalyzed addition of TMSCF3 to alcohols using only 0.5mol% of the preformed carbene as a catalyst (Scheme 14.23). This protocol was also applicable to the addition of other silylated nucleophiles including TMSCN additions to aldehydes and ketones, and imines. ... 

The ability of NHC to activate silylated nucleophiles led to further investigations and useful procedures. Song reported the formation of silyl enol ethers by an NHC-catalyzed silyl exchange reaction that transferred a silyl group from a silyl ketene acetal to a ketone. When aldehydes, rather than ketones, were used as substrates the NHC catalysts promoted a Mukaiyma aldol reaction to give p-hydroxy esters and ketones in good yields. ... 

Silicon Lewis acids have widely been utilized for carbonyl activation, which enables C-C, C-heteroatom, and C-H bond-forming reactions at the carbonyl carbon or the carbonyl-conjugated carbons. Combined use of silicon Lewis acids and silylated nucleophiles provides efficient catalytic systems for these reactions as shown in Scheme 9.1. The initial studies on catalysis by silicon Lewis acids demonstrated that acetalization and reduction of carbonyls were successfully carried out with alkoxysilanes and hydrosilanes, respectively [7e, 93]. Then, strong silicon Lewis acids and new reaction systems were developed for catalytic C-C bond-forming reactions of carbonyls. 

Disilanes also react with aryl halides in the presence of a nucleophilic activator and a palladium catalyst. Upon deprotonation with a base, o-(diphenylphosphino)phenol serves as an activator for disilanes as well as a ligand for a palladium catalyst at the same time to promote the silylation of aryl halides (Scheme... 

Cyclopropyl anionic reagents are also accessible by the fluoride-based nucleophilic activation of the corresponding silylated precursors [53]. Methyl l-trimethylcydo-propanecarboxylate (141, R= COjMe) reacts with acetaldehyde in the presence of BU4NF to give adduct 142, while the aldehyde addition of l-cyano-l-trimethylsUyl-cyclopropane (141, R = CN) is smoothly mediated by benzyltrimethylammonium fluoride (Scheme 5.36). 

---