Synthesis from ketene acetals

Figure 2. Synthesis of orthoesters from ketene acetals and diols.

C-aryl glycosides, 528 C-glycosides, 528 C-glycoside synthesis, 505 fronj enol ethers, 505 by free-radical methods, 507 from ketene acetals, 505 from malonate anion, 505 from 2-pyridylthio glycosides, 385... 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

Hepatite Virus NS3/4A having the pyrrolidine-5,5-trans-lactam skeleton [83], starting from (R)- and (S)-methionine, respectively. The key step is the addition of the proper silyl ketene acetal to an iminium ion, e.g., that generated by treatment of the intermediate 177 with boron trifluoride, which provided the adduct 178 with better diastereoselectivity than other Lewis acids. Inhibitors of hepatitis C virus NS3/4A were efficiently prepared by a similar route from (S)-methionine [83]. The addition of indole to a chiral (z-amino iminium ion was a completely diastereoselective step in a reported synthesis of tilivalline, a natural molecule which displays strong cytotoxicity towards mouse leukemia L 1210 [84]. 

A recent synthesis of P-D lactone (Scheme 13.51) used an enantioselective catalytic approach. A conjugate addition of a silyl ketene acetal derived from an unsaturated ester gave an unsaturated lactone intermediate. The catalyst is CuF-(S )-tol-BINAP.30 The catalytic cycle for the reaction is shown below. 

Clive and coworkers have reported a total synthesis of calicheamicinone, the aglycon of the antitumor agent calicheamicin starting from the Diels-Alder reaction of methyl 3-nitro-propenoate with ketene acetal (Eq. 8.32).54 An asymmetric Diels-Alder reaction between ketene acetal presented in Eq. 8.32 and 3-nitropropenoate derived from (-)-8-phenyl-menthol affords the optically pure adduct, which can be converted into either enantiomer of calicheamicinone (Eq. 8.33).55... 

Likewise, an efficient one-pot multicomponent synthesis of annelated 2-amino pyridines (e.g., 17) utilizing [4+2] cycloadditions has been described <06JOC3494>. The process involves the in situ generation of 1-aza-1,3-butadiene from a palladium-catalyzed coupling-isomerization reaction of aryl halides (e.g., 18) with propargyl V-tosylamines (e.g., 19). The resulting butadiene then undergoes cycloadditions with V.S -ketene acetals (e.g., 20) to form annelated pyridines (e.g., 17). 

Ketene acetal synthesis by /1-elimination of haloacids from halogenated acetals under well controlled conditions using thermal activation (A), ultrasound (US) or micro-wave irradiation [92] (MW) has been described. From a mechanistic point of view, as the TS is more charge delocalized than the GS and the polarity is enhanced during the course of the reaction, a favorable microwave effect can therefore be observed (Eqs. (37) and (38) and Scheme 3.13). 

Another chiral auxiliary for controlling the absolute stereochemistry in Mukaiyama aldol reactions of chiral silyl ketene acetals has been derived from TV-methyl ephedrine.18 This has been successfully applied to the enantioselec-tive synthesis of various natural products19 such as a-methyl-/ -hydroxy esters (ee 91-94%),18,20 a-methyl-/Miydroxy aldehydes (91% ee),21 a-hydrazino and a-amino acids (78-91% ee),22 a-methyl-d-oxoesters (72-75% ee),20b cis- and trans-l1-lactams (70-96% ee),23 and carbapenem antibiotics.24... 

Cyclic ketene acetals, which have utility as co-polymers with functional groups capable of cross-linking, etc., have been prepared by the elimination of HX from 2-halomethyl-l,3-dioxolanes. Milder conditions are used under phase-transfer conditions, compared with traditional procedures, which require a strong base and high temperatures. Solid liquid elimination reactions frequently use potassium f-butoxide [27], but acceptable yields have been achieved with potassium hydroxide and without loss of any chiral centres. The added dimension of sonication reduces reaction times and improves the yields [28, 29]. Microwave irradiation has also been used in the synthesis of methyleneacetals and dithioacetals [30] and yields are superior to those obtained with sonofication. 

General procedure for the synthesis of a-bromovinyl tellurides from ketene stannyl (telluro) acetals To a solution of the appropriate ketene stannyl(telluro) acetal (1.0 mmol) in CH2CI2 (10 mL) cooled at -78°C (at 0°C for 5 h) was added dropwise a solution of NBS (0.445 g, 2.5 mmol) in CH2CI2 (25 mL). Th reaction mixture was stirred for 6 and 12 h (R=H). It was transferred to an Erlenmeyer flask and treated with a solution... 

Having demonstrated the feasibility of the reaction of ketene acetals for the synthesis of unusual or-thoe.sters from glycosides, it was essential to test the... 

Lastly, Corey has developed B LA species 65, derived from zwitterionic oxazaboro-lidine 64 and tri-n-butyltin trifalte, as a novel catalybc system for the enanboselec-bve synthesis of P-lactones from ketene and aldehydes (Scheme 5.81) [152]. The reaction of B LA 65 with ketene generates intermediate A. The subsequent addition of the ketene acetal unit to the coordinated aldehyde (intermediate B) followed by extrusion of the P-lactone completes the catalybc cycle. 

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

For the anionic polymerization of methacrylonitrile (MAN), many initiators have been developed, which include alkali-metal alkyls such as butyllithium [42], triphenylmethylsodium [43], phenylisopropylpotassium [43], the disodium salt of living a-methylstyrene tetramer [44], alkali-metal amides [45], alkoxides [46], and hydroxide [47], alkali metal in liquid NH3 [48], quaternary ammonium hydroxide [49], and a silyl ketene acetal coupled with nucleophilic or Lewis acidic catalysts [50]. However, only a single example of the synthesis of PMAN with narrow molecular-weight distribution can be cited, and the reported number-average molecular weights were much higher than those calculated from the stoichiometry of the butyllithium initiator [42]. 

Hojo et al. [218,308,309] described the trifluoroacetylation of alkenes activated by heteroatom donors such as vinyl ethers and ketene acetals (Eq. 116) the reaction occurs under mild conditions and can be used to prepare bis(trifluoro-acetyl) products from highly activated derivatives [310]. The main use of the products appears to be in the synthesis of trifluoromethyl heterocycles both... 

Chiral fi-lactams. The synthesis of /5-lactams from ketene silyl acetals and Schiff bases (8, 484-485) results in asymmetric induction at C4 in the range 44 78% when optically active Schiff bases are used. An example is shown in equation (l)-... 

The synthesis of natural products by chirality transfer from carbohydrates has been used for a total synthesis of (-)-(7S)-nonactic acid (199). The furanoid glycal (197) was prepared from D-mannose, which is the appropriate chiral precursor (Scheme 46) (80JOC4259). A [3,3]-sigmatropic rearrangement of the silylated ketene-acetal (198) led to the control of the C-2 configuration. The intermediate furanoid glycal was prepared in ten steps from the carbohydrate precursor. 

---