Eschenmoser’s reagent

Only two operations remain. Reaction of the enolic form of aldehyde 162 with Eschenmoser s reagent (H2C=NMe2+I-)62 in the presence of triethylamine provides the desired enal after a simple / -elimination. Finally, cleavage of the remaining tcrt-butyldi-methylsilyl ether with HF pyridine completes the total synthesis of (+)-brevetoxin B (1). 

Substitution reaction with 2-acetonylfurane. A synthesis of nonactic acid ester (4), a budding block of the macrotetrohde nonactin, involves the reaction of 2-acetonylfurane (1) with Eschenmoser s reagent (2). The resulting unstable aldehyde (b) is immediately oxidized and then esterified to give (3). This is converted into the methyl ester of nonactic acid (4) in two steps. ... 

A -Ergostadiene-Sll-ol, 502 A -5a-Ergostene-3 -ol, 502 Ergosterol, 502 Ergosteryl acetate, 100, 595 Ergosteryl acetate tricarbonyliron, 39 Erythionolide B, 215 Eschenmoser cleavage, 232-233 Eschenmoser s reagent, 106 Esterification, 106, 138, 246, 269, 274,... 

Orthoesters are converted into esters with TMS-I. The dimethyl acetal of formaldehyde, methylal, affords iodomethyl methyl ether in good yield (eq 12) 7a (in presence of alcohols, MOM ethers are formed). 7b a-Acyloxy ethers also furnish the iodo ethers, e.g. the protected 8-acetyl ribofuranoside gave the a-iodide which was used in the synthesis of various nucleosides in good yield (eq 13). Aminals are similarly converted into immonium salts, e.g. Eschenmoser s reagent, Dimethyl(methylene)ammonium Iodide, in good yield. ... 

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. 

Scheme 7-39. Reagents and conditions a PI13PCIIOMC, THF, —78°C (91%). b 1 N HC1 (aq), Nal, dioxane (94% at 90% conversion), c TESC1, pyridine, CH2C12, -30°C (92%). d Dess-Martin periodinane, CH2C12. e Et3N, Eschenmoser s salt (97%).

A/V- Di methylmethyleneammonium iodide is commercially available and is known as Eschenmoser s salt .96 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.97 The reagent can be added to a solution of an enolate... 

The tertiary amine, R CH2 NMe2, may be prepared by the reaction of a Grignard or lithium reagent (RMgX or RLi) with Eschenmoser s salt... 

Subsequently, the benzotriazole-based equivalent of Eschenmoser s salt, 25, was prepared in our laboratory. Curiously, we found this substrate not only to be considerably less reactive than 23 or 24, but also less reactive than the Eschenmoser s salt/benzotriazole system, suggesting that 25 is not formed in situ by mixing these two reagents. 

Scheme8.14 Reagents i, (a) NaH, DME, (b) TsOH, PhMe ii, TMSOTf, TEA, Eschenmoser s salt iii, (a) Mel, MeCN, (b) AgOTf, DIPEA, MeCN iv, xylenes.

Replacement of the silyl group by benzyl followed by ozonolysis furnishes ester 1127, which is then converted to thiolactam 1128 with Lawesson s reagent. Eschenmoser sulfide contraction on 1128 gives 1129 in 51% yield. Reduction of the double bond produces a mixture of the desired all-cis pyrrolidine 1130 (77%) and 14% of its C-5 epimer. Removal of the benzyl protecting group under hydrogenation conditions furnishes lactone 1131. 

Scheme 8.15 Preparation of half ester 460. Reagents and conditions a) peracid oxidation b) Me3Si(CH2>20H, DCC, DMAP, CH2CI2/DMF, 80% c) Eschenmoser s base, 75%...

Imines are generally less electrophilic than the corresponding aldehyde but this diminished level of activity can be countered by suitable activation with Lewis acids. Formaldehyde imines are generally stable only at low temperatures and are best formed in situ. However, there are exceptions like Eschenmoser s salt 20. This methylene iminium salt is a relatively stable solid that is now commercially available. The utility of this reagent was illustrated in the Mannich reaction of corrin 19 with 20 to generated 21. 

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