Silyl Nitronates catalysts

The nitroaldol reaction of silyl nitronates with aldehydes promoted by ammonium fluorides, which was originally introduced by Seebach and Colvin in 1978 [24], is a useful method for the preparation of 1,2-functionalized nitroalkanols. Recently, the present authors have succeeded in developing an asymmetric version of high efficiency and stereoselectivity by using a designer chiral quaternary ammonium bifluoride of type 6 as catalyst, which was readily prepared from the corresponding bromide by the modified method C in Scheme 9.5 [25]. 

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

The efficient homogeneous catalysis of chiral ammonium bifluorides of type 15 has been further utilized for achieving an asymmetric Michael addition of silyl nitronates to a,/ -unsaturated aldehydes. Here, chiral ammonium bifluoride 15b bearing a 3,5-di-tert-butylphenyl group was found to be the catalyst of choice, and the reaction of 16a with trans-cinnamaldehyde under the influence of (R,R)- 15b (2 mol%) in THF at —78 °C produced the 1,4-addition product 18 predominantly (18/19 = 24 1) as a diastereomeric mixture (syn/anti = 78 22) with 85% ee of the major syn isomer (Scheme 4.9). Further, use of toluene as solvent led to almost exclusive formation of the 1,4-adduct (18/19 = 32 1) with similar diastereoselec-tivity (syn/anti = 81 19), and critical enhancement of the enantioselectivity was attained (97% ee) [15]. 

Sitro-aldol reaction fl-amino alcohols. Primary nitro compounds form silyl nitronates (1) when treated in sequence with LDA (THF, -78°) and then a silylating reagent. These silyl nitronates undergo aldol condensation with aldehydes in the presence of tetra-n -butylammonium fluoride (there is no reaction in the absence of the catalyst). The products 2 are reduced to /3-amino alcohols (3) in good yield by lithium aluminum hydride (equation 1). Secondary nitroalkanes undergo the same reaction sequence, but the silyl nitronates are less stable and are obtained in only... 

Silyl nitronates undergo enantioselective addition to aromatic aldehydes in the presence of an enantiomerically pure bifluoride derived from (7.103). In this approach the anti-adduct is the major diastereomer formed. Thus silyl nitronate (7.105) undergoes addition to benzaldehyde to give adduct (7.106) with high ee. Alternately the coupling of silyl nitronates can be achieved with high ee using Lewis acids such as copper bis-oxazoline catalyst (7.107) in combination with a fluoride... 

The same year, this group reported an alternative protocol for this reaction, which involved the use of silyl nitronates as activated Michael donors and a novel fluoride ammonium salt 106f as catalyst (Scheme 5.29). This catalyst... 

Based on the enantioselective Michael addition/ISOC (intramolecular silyl nitronate olefin cycloaddition)/lragmentation sequence previously developed by the group of Rodriguez [33a], Shao and coworkers proposed an extrapolation for the construction of spirooxindoles catalyzed by a bifunctional tertiary amine-thiourea catalyst XV between 4-allyl-substituted oxindoles 63 and nitrostyrenes 64 (Scheme 10.21) [33b]. After the addition of TMSCl and EtgN at -30 C, the Michael adduct underwent an ISCX3 to afford the spiro oxime derivatives 65 in very good yields (85-85%), and excellent diastereo (up to >30 1) and enantioselectivities (94-99% ee) after the treatment with TBAF. 

Scheme 6.3 Product range of the addition reactions of ketene silyl acetals to various nitrones activated by thiourea catalyst...

Keywords Catalyst, Alkylation, Allylation, Arylation, Mannich reaction, Carbon-nitrogen double bond, Imine, Nitrone, Aldimine, Organozinc reagents, Silyl ketene acetal, Silyl enol ether, Amine, (3-Amino acid... 

The molecular mechanisms for the nucleophilic addition of lithium enolates and silyl ketene acetals to nitrones in the absence and in the presence of a Lewis acid catalyst to give isoxazolidin-5-ones or hydroxylamines have been investigated by DFT methods at the B3LYP/6-31G level.13 An analysis of the global electrophilicity of the reagents accounts for the strong electrophile activation of the Lewis acid-coordinated nitrone, (g) and the analysis of the local indices leads to an explanation for the experimentally observed regioselectivity. 

Highly porous silica gel served as a support for the TADDOL moiety derived from inexpensive and readily available i-tartaric acid, which provided access to htanium-based Lewis acid catalysts (Heckel, 2000). Such entihes are employed successfully for enantioselective reactions. TADDOLs were covalently attached to the trimethyl-silyl-hydrophobized silica gel, controlled-pore glass (CPG) at about 300 m2 g-1, at a loading of 0.3-0.4 mmol gl (Heckel, 2002). In a carefully monitored mulh-step immobilization procedure, the TADDOLs were titanated to yield dichloro-, diisopropyl-, or ditosyl-TADDOLates. These catalysts were employed in dialkylzinc addihon to benzaldehydes and diphenyl nitrone addihon to 3-crotonyloxazolidinone, a [3+2] cycloaddition. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

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