Amidomercuration

Considering the monoaminomercuration-demercuration of 1,4-hexadiene with /V-me-thylaniline leads to V-methyl-lV-(l-methylpent-3-enyl)aniline, the stereoselective synthesis of /V-alkoxycarbonyl or /V-tosyl s-2,5-dimethylpyrrolidine from the same diene has been explained172 on the basis of an initial amidomercuration reaction on the terminal bond followed by the second addition of mercury(II) salt to the internal double bond, on the less sterically hindered site (equation 171). 

Chiral rra s-2,5-dialkylpyrrolidines, which were used for the synthesis of ant-venom pyrrolizidines, were prepared in the following manner, d-Alanine was transformed into an pentenylamine which, upon intramolecular amidomercuration, yielded 15 (90TA561 92JOC4401). From a protected AA amide, after a Grignard reaction and treatment of the aminoketone with ethyl acetoacetate, the tetrasubstituted pyrrole 16 was obtained [93H(35)843],... 

Cyclization by amidomercuration has been reported (391). Reaction of N-methoxycarbonyl-6-aminohept-l-ene (211) with mercuric acetate gave the organomercurial (212). Reductive coupling of 212 with l-decen-3-one in the usual way gave the cis and trans isomers (213). Successive treatment of 213 with ethanedithiol, Raney nickel, and ethanolic hydrogen chloride afforded ( )-sole-nopsin A (Id, 2 parts) and its isomer (Ic, 3 parts), which were separable by preparative gas chromatography (GC) (Scheme 5) (391). 

The synthesis of indolizidinone STM (Scheme 15) involved a transannular amidomercuration of lactam 38. Subsequent stereospecific reductive trapping with acrylonitrile afforded the key indolizidinone 39 in 56% yield 85 Further manipulation provided 37 which antagonized, in a dose-dependent fashion, the stimulatory effect of tuftsin in an opsonized sheep red blood cell assay. 

There are several methods available for the electrophilic addition of hydrogen and nitrogen to alkenes, dienes and alkynes. While the direct electrophilic addition of amines to these substrates is not feasible, aminomercuration-demercuration affords a very useful indirect approach to such amines. The addition of amides to C—C multiple bonds can be effected directly through the Ritter reaction or by the less direct, but equally useful, amidomercuration-demercuration process using either nitriles or amides. Similarly, H—N3 addition to alkenes can be carried out directly or via mercuration to produce organic azides. 

Amidomercuration using nitriles has received the most attention. This reaction commonly employs mercury(II) nitrate with the nitrile as solvent. Acetonitrile is the most widely used nitrile, but RSCN and R2NCN can also be employed.243... 

A variety of alkenes undergo successful amidomercuration, but alkenes of the type R2C CH2 and R2C=CHR fail to react in the anticipated fashion.243-245 While rearrangements have been observed with a- and fi-pinene,243 3,3-dimethyl-1 -butene reacts normally.244... 

There appears to be only one example of intramolecular amidomercuration using an unsaturated nitrile (equation 175),247 and no examples of the amidomercuration of dienes or alkynes using nitriles. 

Amides can also be utilized for amidomercuration.242248-249 The reaction is usually run using equivalent amounts of the alkene and Hg(NCb)2, plus 10 equiv. of amide in refluxing dichloromethane (equation 176). 

Intramolecular amidomercuration of unsaturated amides and subsequent reduction is a very useful approach to cyclic amides (equations 177 and 178).242 Mercuric acetate has been employed in all such reactions to date. The reaction is often highly regio- and stereo-selective.230-233... 

Sulfonamides can also be employed in amidomercuration when mercury(II) nitrate is utilized as the mercury salt (equation 179).234... 

Intramolecular amidomercuration of carbamate derivatives to generate 2,6-disubstituted piperidine systems (equation 113 and Table 31) proceeds with low selectivity under conditions of kinetic control (cis.trans = 40 60),246 248 but cyclization under conditions of thermodynamic control highly favors the cis isomer (cis. trans > 98 2).246 Interestingly, only the cis isomer was isolated from cyclization with phe-nylselenenyl chloride in the presence of silica gel.216 ... 

When aq. ammonia acts upon mercurous chloride the latter is oxidized to white amidomercuric chloride, H2N.HgCl, and metallic mercury. In symbols ... 

Allyl phosphates, 506 Allylsilanes, 43, 71-72, 529, 575 Allyl sulfones, 512 Allyltitaniiun ate complexes, 376-377 Allyltri-n-butyltin, 15-16 Allyltrimethylsilane, 16-20, 532 Allyltrimethyltin, 20-21 Almusone, 51 Alpine Boranc, 429 Alumina, 22-24 Aluminum amalgam, 24-25 Aluminum ate complexes, 17 Aluminum chloride, 25-28, 100 Aluminum chloride-ethanethiol, 28-29 Aluminum isopropoxide, 29, 296 Amidoalkylation, 16-17 Amidomercuration, 317 Animation, 221 Amino acid esters, 360... 

Amidomercuration. The reaction of alkenes with anhydrous Hg(N03)2 in the presence of primary amides in CH2C12 followed by demercuration (NaBH4-NaOH- -BuNH2) results in N-substituted amides in 45-99% yield (equation I). 

Intramolecular amidomercuration. " Kinctically controlled amidomercuration IHg(OAc), THF] of the 8-alkenylcarbamatc 1 followed by reduction results in highly stereoselective cyclization to /ran.v-2,5-dimethylpyrrolidines (equation I). Amidomercur-... 

The situation is reversed in the e-alkenylcarbamate (2) Amidomercuration with Hg(OAc), in THF results in a mixture of cis- and fra .s-products, whereas thermodynamically controlled reaction with H g(OCOCF,) in CH,NO, results in highly selective cyclization to a /.v-2.6-dimethylpipcri(tline (equation II). 

Phase transfer reagents sometimes avoid deoxymercuration during the reduction step, as with the products (18) to (20) from hydroxymercuration, amidomercuration and from spiroacetals. ... 

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