Silyl ketene aminals

Scheme 50). An alternate approach to the oxindole C3 to C7 bicyclic core found in members of welwitindolinone family has been reported by the Shea and coworkers who set the C3 linkage via a Znl2 promoted coupling of silyl ketene aminal 204 with functionalized furan 205 (Scheme 51) [120]. An intramolecular cycloaddition between C3 tethered furan of 206 and C7 pendant a,p-imsaturated ester closed the bridged oxindole scaffold of 207 in 41% yield. 

Silver(I) salts are often utilized as catalysts for addition reactions. Kozmin and Sun have recently shown that AgNTf2 is a catalyst of choice for the hydroamination of siloxy alkynes with either secondary amides or carbamates to give silyl ketene am-inals [34]. The addition occurs in a syn selective manner, for instance, the reaction of siloxy alkyne (24) with carbamate (25) produces silyl ketene aminal (26) in 86% yield at room temperature under the influence of 1 mol% of AgNTf2 (Scheme 18.9). A six-membered chelated transition state is proposed to explain the high syn selectivity. Diastereoselective bromohydroxylation and bromomethoxylation reactions of cinnamoyl compounds possessing a chiral auxiliary are also effectively promoted by silver(I) salts such as AgNOs [35]. The asymmetric halohydrin reaction has been successfully applied into stereoselective syntheses of (-)-chloramphenicol and (+)-thiamphenicol. Csp-H iodination [36], hydrosilylation of aldehydes [37], and deprotection of TMS-alkynes [38] are also catalyzed by silver (I) salts. 

When sensitive functional groups were present, a successful borylation reaction can still be carried out provided the sensitive groups were protected prior to addition of the organolithium reagent. To this end, the borylation of A-methyl-4-bromooxindole was accomplished in a four-step process (Scheme 6.23) [46]. In the first step, the oxindole was converted into a silyl ketene aminal. The second and third steps were focused on the metalation of the intermediate through the addition of BuLi followed by borylation. The final step was regeneration of the oxindole with retention of the arylboronate fragment. 

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... 

Azodicarboxylate esters are the reagents of choice for electrophilic N-amino amination leading to hydrazine derivatives. Besides Grignard reagents and alkyl or aryl lithium compounds,enolates and silyl enol ethersderived from ketones have been aminated by this method. In particular, di-r-butyl azodicarboxylate has been reacted with a variety of chiral enolates (Scheme I9)i03->o and chiral silyl ketene acetds (Schemes 20 and to afford a-hydrazino acid derivatives with high dia-... 

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 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). 

Isomerization of silyl ketene acetm by migration of the silyl group from ox alkanoic esters, is very facile (5 min. r Friedel-Crafts acylation. The recovered and reused without decrease Cleavage of small heterocyeles. opened with amines when catalyzed b with the pressure reaction."... 

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