Fluoride-mediated aldehyde addition

Scheme 5.37 Fluoride-mediated aldehyde addition of oxiranyl- and aziridinylsilanes.

Firstly, the possibility of generating an a-aminomethyl anion equivalent under mild and neutral conditions and in the presence of the electrophilic receptor via the fluoride ion cleavage of the Si-C bond was investigated by Patel and Joule,11 who observed the addition product of the anion to the starting material. Katritzsky and Sengupta12 then found that fluoride-mediated desilylation could be carried out in the presence of an aldehyde, allowing the facile synthesis of aminoethanols. 

The second most important synthetic application of silyl nitronates in C-C bond-forming reactions is their fluoride-mediated addition to aldehydes. Silyl nitronates from secondary nitroalkanes lead to free nitro aldols such as (4), while those from primary nitro alkanes give silylated products. In contrast to the classical Henry reaction, the silyl variant is highly diastereose-lective with aldehydes, furnishing e yfAro-0-silylated nitro aldols (e.g. 5). It is important that the reaction temperature does not rise above 0 °C, otherwise threo/erythro equilibration takes place. The same erythro-nitio aldol derivatives are available by diastere-oselective protonation of silyloxy nitronates (eq 3) (usually the dr is >20 1), while the nonsilylated fAreo-epimers (R = H, dr = 7 3-20 1) are formed by kinetic protonation of lithioxy lithio nitronates in THF/DMPU (eq 4). Other recent modifications of the nitroaldol addition using titanium nitronates or ClSiRs in situ are less selective. It should also be mentioned that there are recent reports about the enantioselective addition of nitromethane to aldehydes in the presence of rare earth binaphthol complexes. 

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). 

A stereoconvergent reaction without any correlation between the geometry of the enolate and simple diastereoselectivity occurs when fluoride ions are used to induce an aldol addition of enolsilanes to aldehydes. For example, both a 99 1 and a 9 91 mixture of the following (Z)/( )-enolsilane lead predominantly to the formation of the. un-adduct in a highly selective manner, when the addition is mediated by tris(diethylamino)sulfonium difluorotrimethylsili-conate27,28. 

Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

P, P] Seebach and Brock reported the dichlorodiisopropoxytitanium-mediated addition of the trimethylsilyl enol ether of cyclohexanone to /3-nitrostyrenes (83). The initial products generated are nitronic esters 39.1-39.3. Separation followed by fluoride-induced desilylation of these intermediates yields the corresponding syn and anti nitroketones. The results of this study are summarized in Scheme 39 and Table 12. Anti isomers are obtained in moderate diastereomeric excess. Moreover, the method is complementary to the additions of similar substrates by way of their lithium enolates (2) or enamines (vide supra), which provide the syn diastereomers. Further reactions of the intermediate nitronic esters were briefly explored. For example, addition of aldehydes and activated olefins provides stereoselectively the products from nitroaldol and [3 + 2] cycloadditions. 

The addition of PhSeCF2TMS to carbohydrate-derived a-chiral aldehydes provided the corresponding difluoro(phenylselenyl)-methyl adducts with acceptable diastereoselectivities (eqs 9-15). Tetramethylammonium fluoride (TMAF) appeared as the appropriate mediator for these reactions (eqs 9-13 and eq 15). The benzoyl-protected aldehyde required the use of tetrabutylammo-nium difluorotriphenylsilicate (THAT) as a mediator to give the addition product only in low yield (eq 14). The two-step procedure (the addition of TBAF in the second step) was used to convert the OH/OTMS mixture initially obtained to the free alcohols (eqs 9 and 13-15). For benzyl- and MOM-protected aldehydes, a warm-up to room temperature was sufficient to afford alcohols in high yields (eqs 10-12). 

In the Mukaiyama addition of the aldol reaction [16], silyl ketene acetals or silyl enol ethers are added to aldehydes in a reaction mediated by Lewis acids or fluoride. Here again the Z-syn correlation is sometimes not observed [69, 70]. Thus, the Z-syn, E-anti correlation seems to be a rule with several exceptions [71]. 

Silver(I) complexes with Tol-BINAP (270) were used by Yamamoto and coworkers for mediating diastereoselective and enantioselective Mukaiyama aldol additions. According to the authors conclusion, the mechanism does not involve transmetallation to silver enolates but follows the usual carbonyl group activation [135]. Hoveyda and coworkers used silver(II) fluoride in the presence of a dipeptide-type ligand for enantioselective additions of silyl enol ethers to a-keto esters [136]. The reaction of 2-trimethylsilyloxyfuran with aromatic and aliphatic aldehydes was catalyzed with chromium salen complex in the presence of protic additives like isopropanol [137]. Various protocols of enantioselective Mukaiyama aldol reactions that use water as cosolvent have been elaborated ... 

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