Silyl enol ethers iodides from

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

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. 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

After florisil (magnesium-silicate) filtration and concentration, crude 18 was treated with a THF solution of a 1 1 mixture of sodium iodide and mcte-chloroperoxybenzoic acid (MCPBA) yielding in 67 % (from 5) the a-iodo ketones 6.8 The ratio of diastereomers in this mixture was not described further. Mechanistically MCPBA oxidizes the iodide ion to an iodoniumion-species, which reacts with the double bond, generating intermediate 21. After TMS is removed the tricyclic iodonium ion collapses to desired 6. In contrast to this transformation the researchers observed no useful yields by direct treatment of the silyl enol ether with molecular iodine. 

The silyl enol ether may be obtained from the Fluka Chemical Corp., 255 Oser Avenue, Hauppauge, NY 11788. Alternatively, it may be prepared by the following modification of the procedure of Walshe and co-workers.2 The Walshe procedure is followed exactly with 36 g (0.30 mol) of acetophenone, 41.4 g (0.41 mol) of tri ethyl amine, 43.2 g (0.40 mol) of chlorotri-methylsilane, 60 g (0.40 mol) of sodium iodide, and 350 nt of acetonitrile. After extraction, the organic layer is dried over potassium carbonate and then concentrated with a rotary evaporator under reduced pressure. The crude product is a mixture of 97% of the desired silyl enol ether and 3% of acetophenone, as shown by gas chromatography. The crude product is distilled in a Claisen flask at a pressure of about 40 mm. After a small forerun (ca. 3... 

Reaction with a-chloroacylsiianes. Methylmagnesium iodide reacts with a-chloroacyltrimethylsilanes (2), readily available from silyl enol ethers (1), to give -ketoalkyltrimethylsilanes (3). The reaction involves rearrangement of the silyl group to the adjacent carbon atom. ... 

Padwa and coworkers applied the silver(I)-promoted alkylation of silyl enol ethers to synthesis of substituted furans [19]. For example, treatment of various trimethylsilyl enol ethers of cycloalkanones 44 and (F)-2,3-diiodo-l-(phenylsulfonyl)-l-propene (45) with 2 equiv. AgBF4 gives alkylated products 46 resulting from Sn2 displacement of the terminal iodide. These compounds 46 further cyclize with triethylamine to produce the 2-phenylsulfonylmethyl substituted furans 47 (Sch. 10) [19a]. 

The first examples of asymmetric Heck cyclizations that form quatemaiy carbon centers with high enantioselectivity came from our development of an asymmetric synthesis of the pharmacologically important alkaloid (—)-physostigmine (184) and congeners (Scheme 6-31) [68]. In the pivotal reaction, (Z)-2-butenanilide iodide 182 was cyclized with Pd-(5)-BINAP to provide oxindole 183 in 84% yield and 95% ee after hydrolysis of the intermediate silyl enol ether. With substrates of this type, cyclizations in the presence of halide scavengers took place with much lower enantioselectivity [68]. 

Under the conditions used for the generation of silyl enol ethers of symmetrical ketones, unsymmetrical ketones give mixtures of structurally isomeric enol ethers, with the predominant product being the more substituted enol ether (eq 20). Highly hindered bases, such as lithium diisopropylamide (LDA), favor formation of the kinetic, less substituted silyl enol ether, whereas bro-momagnesium diisopropylamide (BMDA) generates the more substituted, thermodynamic silyl enol ether. A comhination of TMSCl/sodium iodide has also been used to form silyl enol ethers of simple aldehydes and ketones as well as from a,p-unsaturated aldehydes and ketones. Additionally, treatment of a-halo ketones with zinc, TMSCl, and TMEDA in ether provides... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

---