Silyl enol ethers amination

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... 

Use of trimethylsilyl triflate to bring about Piunmeier rearrangement requires the presence of a base such as a tertiary amine (vide supra equations 15 and 26). In some instances, involving attempts to alkylate Pummerer intermediates with silyl enol ethers under such conditions, the base has been found to compete as a nucleophile. In the absence of the silyl enol ether, amine addition can be very efficient. For example, treatment of methallyl phenyl sulfoxide with diisopropylethylamine and trimethylsilyl inflate in dichloromethane (equation 29) at 0 C yields the ammonium triflate indicated in 91% yield. Other tertiary amines which undergo this reaction include niethylamine and Af,Af-diethyltrimethylsiI-amine. In the latter case with allyl phenyl sulfoxide as the substrate and a mildly acidic wotk-up, the Mannich derivative shown in equation (30) can be obtained in 90% yield. ... 

This section covers cyclizations to the pyrrole nucleus catalyzed by other metals (Ti, Mn, Ru, Pd, Pt, Zn, In). Dembinski and co-workers used zinc(II) chloride as ligand-free catalyst for the microwave-assisted cyclization of homopropargyl azides 26 to afford substituted pyrroles 27 (Scheme 8) [62]. A similar methodology for the synthesis of 2,4,5-trisubstituted pyrroles was described by Driver et al. employing substituted 1-azidobuta-l,3-dienes in a cyclization reaction using catalytic amounts of zinc(ll) iodide [63]. A three-component zinc-catalyzed one-pot cyclization of aromatic and aliphatic propargylic acetates, silyl enol ethers, and primary amines to substituted pyrroles has been described by Zhan et al. The reaction sequence includes propargylation of the silyl enol ether, amination, 5-exo-(7ig-cyclization, and isomerization [64]. Hiroya and co-workers have shown... 

As in the Japp-Klingemann reaction, when Z is an acyl or carboxyl group (in the case of R2CH—Z), it can be cleaved. Since oximes and nitroso compounds can be reduced to primary amines, this reaction often provides a route to amino acids. As in the case of 12-4, the silyl enol ether of a ketone can be used instead of the ketone itself. Good yields of a-oximinoketones (20) can be obtained by treating ketones with fert-butyl thionitrate. ... 

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. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

The oxidation of silyl enol ethers with the osmium tetroxide-amine oxide combination also leads to a-hydroxyketones in generally good yields.147... 

The mechanism of this transformation is a matter of debate, and may vary with the structure of the heteroanalogous carbonyl compound employed. Although a Diels-Alder-type process is conceivable [246], a Lewis acid-induced addition of the silyl enol ether moiety in 2-453 followed by a cyclizahon through a nucleophilic intramolecular attack of the amine and subsequent elimination of methanol is assumed in this case [247]. 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allyhc strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allyhc amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allyhc alcohols with an alkyl group R cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R cis) substituent (substrates 39h and 39i, see Figure 4). 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

As depicted in Scheme 1.1.2, the silyl ketones (S)-ll of high enantiomeric purity were converted into the Z-configured silyl enol ethers (S) -12, which were used in the aminomethylation step by treatment with dibenzyl(methoxymethyl)amine in the presence of a Lewis acid. The silylated Mannich bases S,R)-13 were obtained in excellent yields and diastereomeric excesses (de = 92-96%). Finally,... 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

However, the presence of an alkene exo to the chain 40 stops the reaction, presumably because the 120° angle holds the ends too far apart. The solution is conjugate addition of an amine 41 the acyloin then works well 42 and the synthesis of the flavouring compound corylone 43 is completed simply by a silica column.7 Hydrolysis of the silyl enol ethers leads to elimination of Me2NH under the slightly acidic conditions. 

Titanium enolates. These enolates have generally been prepared by transmet-talation of alkali-metal enolates or silyl enolate ethers. Surprisingly, Evans et al. find that a titanium enolate can be prepared directly from the oxazolidinone 1 by reaction with TiCl4 (1 equiv.) in CH2C12 and shortly thereafter with ethyldiisopropyl-amine (or triethylamine) at 0°. The enolate may actually be an ate complex (2a)... 

Tanaka and co-workers <19960M1524> observed the insertion of acid chlorides into SCBs in the presence of palladium or platinum catalysts. When an excess of amine was employed, SCBs undergo ring-expansion reactions to afford cyclic silyl enol ethers in good to excellent yields (Scheme 49). 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

The nitrido complex was applied to the direct asymmetric animation with a silyl enol ether as a substrate. Although several examples for achiral aminations of silyl enol ethers have been reported [32], an asymmetric version of reagent-controlled reaction has not appeared except for the one recent example [33] and the diastereoselective reactions with silyl enol ethers having a chiral auxiliary [34], The amination, which is presumed to take place via an aziridine intermediate [5g, lid,32], proceeded smoothly to give the A-tosylated a-aminoketone in 76% yield with 48% ee. When the same silyl enol ether was treated with complex 15 under Carreira s condition, the TV-trifluoroacetylated a-aminoketone was obtained in 58 % yield with 79 % ee (Scheme 24). 

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