Acetals allyl silane addition

The synthesis began with (+)-citronellal 4, each enantiomer of which is commercially available in bulk. After protection and ozonolysis, the first singly-aminated stereogenic center was installed by enantioselective, and therefore diastereoselective, addition of 5 to the azodicarboxylate 6, mediated by the organocatalyst 7. Reductive cleavage of the N-N bond followed by acetal methano lysis converted 8 to 9. Ionization followed by allyl silane addition then delivered 11, having the requisite axial alkyl branch. 

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. 

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). 

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... 

In the presence of titanium(IV) chloride or aluminum chloride, carbonyl compounds such as aldehydes, ketones, acetals, and acid halides are allylated with allylic silanes (eq (12)) [9]. The conjugate addition to enones is also reported (eq (13)) [10],... 

The most useful of all allyl anion equivalents are the allyl silanes.20 This is because it is easy to make them regioselectively, because they do not undergo allylic rearrangement (silicon does not do a [1,3] shift) and because their reactions with electrophiles are very well controlled addition always occurring at the opposite end to the silicon atom. Symmetrical allyl silanes can be made from allyl-lithiums or Grignards by displacement of chloride from silicon. A useful variant is to mix the halide with a metal, e.g. sodium, and Me3SiCl in the same reaction, rather after the style of the silicon acyloin reaction,21 as in the synthesis of the acetal 80. 

The (dienyl)iron cations of type (248) and (265) are susceptible to reaction with nucleophiles. For the (cyclohexadienyl)iron cations, nucleophilic attack always occurs at a terminal carbon, on the face of the ligand opposite to the metal, to afford -cyclohexadiene products. Typical nucleophiles used are malonate anions, amines, electron-rich aromatics, silyl ketene acetals, enamines, hydrides, and allyl silanes intramolecular nucleophilic addition is also possible. The addition of highly basic organometallic nucleophiles (Grignard reagents, organolithiums) is often problematic this may be overcome by replacing one of the iron carbonyl... 

Following from the examples of allyltrichlorosilanes 21.5, Denmark introduced the related eno)g4 richlorosilanes 21.97 (Scheme 21.13) to cany out Mukaiyama-lype nucleophilic additions to carbonyl compounds. " According to Mayr s nucleophilicity scale, silyl enol ethers derived from aldehydes and ketones and, in particular, silyl ketene acetals are even more powerful nucleophilic reagents than the respective allyl silanes. Indeed, the aldol-type addition of trichlorosilyl enol ethers 21.97a-d to aldehydes 21.4 proceeds readily at room temperature without a catalyst exhibiting simple first-order kinetics in each component (Scheme 21.13), which contrasts with the lack of reactivity of allyl silanes in the absence of a catalyst. 

Nucleophilic additions to a,3-dialkoxy aldehydes via allyl silanes (eq 3) or silyl ketene acetals (Mukaiyama reaction) (eq 4) exhibit similarly high selectivities. a-Thio aldehydes also react under MgBr2-catalyzed Mukaiyama conditions with efficient stereocontrol (eq 5). ... 

Silyl-substituted ally methoxyacetate 1 undergoes the Claisen-Ireland rearrangement to diastereoselectively give optically active allylic silane 2 as exemplified by Scheme 5.1. The resulting silane is employed for asymmetric addition to both aliphatic and aromatic acetals 3a and 3b in the presence of MejSiOTf, giving rise to homoallylic ethers 4a and 4b, respectively, with high diastereo- and enantioselec-tivities [4]. The whole sequence of reactions is an example of 1,4- and 1,5-remote... 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Several groups have employed 1,4-additions of nucleophiles, radicals or silanes to allyl acrylates. The intermediate sUyl ketene acetals then underwent Ireland-Claisen rearrangement (Scheme 4.55). 

---