Acetals allylic silanes

LPDE mediated allylic substitutions have been investigated widely. Substitution reaction of allylic alcohols with silyl ketene acetals, allyl silanes, indoles, methoxymethyl vinyl ether, trimethylsilyl azide, trimethylsilyl cyanide, and propar-gyl silanes proceeds with LPDE (Scheme 3.9) [32, 33]. An experiment with allylic alcohol (5,6) proved that these reaction proceeds via generation of allylic carbocation (Scheme 3.10). Also with a combination of LPDE and AcOH (1 mol%), more efficient allylic substitutions proceed (Scheme 3.11) [34]. 

Scheme 9.4. Reactions of Alkenyl and Allylic Silanes with Aldehydes, Ketones, Acetals,...

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

Section B of Scheme 9.4 gives some additional examples of Lewis acid-mediated reactions of allylic silanes with aldehydes and acetals. 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

This reaction, also, has been performed diastereoselectively.461 Allylic silanes R.2C=CHCH2SiMe3 can be used instead of silyl enol ethers (the Sakurai reaction). 462 Similarly, silyl ketene acetals, e.g., 56, give 8-keto esters, in MeN02 as solvent, for example,463... 

Mikami et al. also investigated the addition of ketene silyl acetals. They found that addition of the silyl enol ether of acetone and allylic silanes did not result in the synthesis of substituted l,2-dihydro[60]fullerenes [218a,220], In 1997, Mikami et al. [221] reported the photoaddition of allylic stannanes that leads to monoallylation of C6o (Scheme 13). 

In the presence of Lewis acids allyl silanes and stannanes react with epoxides generally at the sterically less demanding carbon atom. Other electron-rich alkenes, such as ketene acetals, can also be used as nucleophiles. The strong Lewis acids required might, however, also lead to rearrangement of the epoxide before addition of the nucleophile can occur (last reaction, Scheme 4.72). 

Allyl silanes react with a wide variety of electrophiles, rather like the ones that react with silyl enol ethers, provided they are activated, usually by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trim ethyls ilyl tri-flate. Electrophiles include the humble proton generated from acetic add. The regiocontrol is complete. No reaction is observed at the other end of the allylic system. All our examples are on the allyl silane we prepared earlier in the chapter. 

A closely related reactive oxonium ion can be prepared by Lewis-acid-catalysed breakdown of the corresponding acetal. Alternatively, especially if the acetal is at least partly a silyl acetal, the same oxonium ion can be produced in situ using yet more silicon in the form of TMSOTf as the Lewis acid catalyst. All these intermediate oxonium ions act as powerful electrophiles towards allyl silanes producing homoallylic alcohols or ethers. 

The regio control that results from using an allyl silane to direct the final elimination is illustrated by this example of an intramolecular reaction on to an acetal promoted by tin tetrachloride. The same reaction can be run in the absence of silicon but the intermediate cation can then lose a range of protons to produce five different products ... 

The cyclic acetal is a protected form of the hydroxy-aldehyde and oxidation under acidic conditions (Cr03 in H2S04) gives a good yield of the spirocyclic lactone. In the whole process from allyl silane to lactone, the allyl silane is behaving as a d3 synthon or homoenolate. 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

Silyl group transfer can also be used to functionalize chain ends. For example, allyl silanes, silyl ketene acetals, and silyl enol ethers [301-304] generate polymers with terminal allyl and methacrylate groups [Eq. (103)]. This type of transfer becomes degradative (termination) if reinitiation with silyl halides is not possible. 

As mentioned above, acetals are much more reactive acceptors in la-catalyzed ally-lation than aldehydes or ketones. Intramolecular allylation has been examined for the synthesis of highly functionalized piperidine derivatives [50]. Catalytic use of la effects cyclization of nitrogen-containing acetal 23 bearing an allylic silane to give piperidine 24 with moderate selectivity (Sch. 19). 

The addition of allyltributylstannane to aldehydes can also be effected with equimolar amounts of MeSiCl3 or MeSiCl(OMe)2 (Eq. 13) [21]. The initial product is the silyl ether which is hydrolyzed in the aqueous work-up. An allylic silane intermediate was shown not to be involved in the addition. The reaction with benzaldehyde could be accomplished with 0.33 equiv. of trichlorosilane but at a much slower rate. The product of this addition was cleaved by treatment with KF or aqueous acetic acid in THE... 

Allylic silanes react with gem-diacetates in the presence of InCl3 to give a homo-allylic acetate or with dimethyl acetals and TMSOTf in an ionic liquid to give the homoallylic methyl etherJ Allylic alcohols can be treated with TMS—Cl and Nal,... 

The acetal is a masked aldehyde which is attacked by the allyl silane to give a homoallylic ether. 

Scheme 9 demonstrates the further synthetic application of the thus obtained N,0-acetals. Substitution of the alkoxy or acyloxy group by nucleophiles like enol ethers, enol esters, enamines, other electron-rich olefins, CH-acidic compounds, electron-rich aromatics, isocyanides, trimethylsilyl cyanide, organometallics, vinyl and allyl silanes, hydroxy functions, or trialkylphosphites either catalyzed by Lewis acids or proton acids leads to the product of the amidoalkylation reaction (path a). In the presence of stereocenters as control elements, diasteroselective amidoalkylation reactions can be performed as shown in a large number of examples. On the other side, as Nyberg showed for the first time [196], elimination with formation of enecarbamates [208] and enamides [196,208,209] followed by reaction with electrophiles or nucleophiles (path b) also is possible. 

Similarly, at a carbon anode in 1 1 MeOH-THF, anodic cyclization of allylsilane enol ether (XCIX) proceeded stereoselectively to give (C) [Eq. (63)]. The use of allyl silanes as the unsaturated nucleophilic component in such radical-cation cyclizations proved to be beneficial, though the exact mechanistic details remain somewhat speculative [147]. The method represents an improvement over earlier methods involving anodic cyclization of alkenyl-substituted enol acetates [148]. 

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