Acetals, silyl ketene amination

Scheme 2.9 gives some examples of use of enantioselective catalysts. Entries 1 to 4 are cases of the use of the oxazaborolidinone-type of catalyst with silyl enol ethers and silyl ketene acetals. Entries 5 and 6 are examples of the use of BEMOL-titanium catalysts, and Entry 7 illustrates the use of Sn(OTf)2 in conjunction with a chiral amine ligand. The enantioselectivity in each of these cases is determined entirely by the catalyst because there are no stereocenters adjacent to the reaction sites in the reactants. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

Sulfonyl chlorides having an a-hydrogen are unstable under basic reaction conditions and can give variable results [96,97]. For base-labile sulfonyl chlorides, the use of O-silyl ketene acetals as scavengers for HC1 has been recommended [96]. Table 8.7 lists some illustrative procedures for the preparation of sulfonamides from primary amines on solid phase. Further examples have been reported [98-101]. 

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 (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 aUyl silanes intramolecular nucleophilic addition is also possible. The addition of highly basic organometaUic nucleophiles (Grignard reagents, organolithiums) is often problematic this may be overcome by replacing one of the iron carbonyl... 

Asymmetric electrophilic amination reactions using silyl ketene acetals 1 and di-tert-butyl azodicarboxylate (DBAD) finally lead to a-hydrazino 3 and ( )-a-amino acids 415. 

Ethyl (5)-lactate has been the primary source of chirality in several syntheses of amin-odeoxycarbohydrates. The derivative 101 of 2-amino-2-deoxy-L-lyxonic acid is the major product of condensation of 2-O-benzyl L-lactaldehyde with silyl ketene acetal 100. The derived ester 101 can be converted into lactone 102 (O Scheme 47) [239] an intermediate for the s)mthesis of L-daunosamine and L-vancosamine [240,241]. L-Mannose and L-altrose... 

Homoallylic amines and fi-amino esters. Aldimines are attacked by allylstannanes and silyl ketene acetals when Zr(OTf) or Hf(OTf)4 is present. 

Silyl ketene acetals are aminated by the ethoxycarbonylnitrene precursor Et02CN(TMS)OTMS to give a-ethoxycarbonylamino esters via aziridines in fair to good yields (see Eq. 124).105... 

Silyl ketene acetals are animated by the hypervalent iodine reagent TsN=IPh (Eq. Ill),173 and by Et02CN(TMS)(OTMS) (see Eq. 124 in the section on amination of lactones).105... 

Amide enolates mirror ester enolates in their amination reactions. Secondary amides can be used by employing two equivalents of the base, but yields in the only example found in the literature are low to fair.212 Ketene aminals react with azodicarboxylic esters at room temperature, but yields are low (Eq. 125).251 Eq. 126 shows the application of the copper-catalyzed enantioselective addition of mixed ketene acetal/aminals to azodicarboxylic esters previously described for silyl enol ethers in Eq. 94.252 Increasing bulk of the R substituent in the substrate causes partial or complete amination on the pyrrole, as evidenced by the yields of products 60 and 61 as R is varied. 

The TiCU-mediated reaction of enol silanes with imines was first introduced by Ojima and coworkers in 1977. The reaction was then extended to several similar substrates, i.e. nitrones, ot-methoxycarba-mates, aminals, 4-acetoxyazetidin-2-one, 40 anj to different Lewis acids, i.e. SnCU, TiCU-(0PH)2, catalytic ZnX2, catalytic TMSOTf, ° to give good yields of the addition products with low levels ( 80 20) or a complete lack of simple stereoselection. Moderate to good anti selectivities were reported in the addition of silyl ketene acetals to imines under particular reaction conditions (equation 9) significant results are summarized in Table 4. 

In addition to alkenes or compounds with strained double bonds, 1,2,4-triazines react readily with electron-rich dienophiles such as enol ethers, enamines, enaminones, vinyl silyl ethers, vinyl sulfides, vinyl acetate, and ketene derivatives (see also Ilouben-Weyl, Vol. E7b, p 471 ff). It has been shown195,403,404 that oxo compounds and catalytic amounts of amines can be used instead of enamines however, water formed in the reaction can result in the formation of side products.403... 

In the rearrangement of allyl fluoroacetates, trialkylsilyl triflates have been introduced as a new reagent for the Z-selective generation of silyl ketene acetals485. Thus, when (T)-crotyl fluoroacetates are treated at ambient temperatures with a trialkylsilyl triflate in the presence of a tertiary amine, rearranged products with a svn relationship are preferentially obtained. The ketene acetal intermediates cannot be isolated and the geometry has been deduced from the stereochemistry of the products. The selectivity of this process improves in the order triisopropyl > ferf-butyldimethylsilyl > rerf-hexyldimethylsilyl > trimethylsilyl a triethylsilyl (see Table 11). 

Shibasaki [89a] has reported an asymmetric synthesis of (-h) PS-5 by using the boron enolate-imine condensation reaction. The most notable features of this approach were that the correct absolute stereochemistry at C3-C4 of the p-lactam ring was produced in a highly diastereoselective fashion and imines derived from aliphatic amines could be used in this reaction in a similar way to the silyl ketene acetal approach (Scheme 32). 

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