Aminomercuration

Chemical Designations - Synonyms Albus Aminomercuric chloride Ammoniated mercury Mercuric chloride, ammoniated Mercury ammonium chloride Mercury (II) chloride ammonobasic Chemical Formula HgNHjCl. 

Ammonia can be added to double bonds (even ordinary double bonds) in an indirect manner by the use of hydroboration (15-16) followed by treatment with NH2CI or NH2OSO2OH (12-29). This produces a primary amine with anti-Markovnikov orientation. An indirect way of adding a primary or secondary amine to a double bond consists of aminomercuration followed by reduction (see 15-3 for the analogous oxymercuration-demercuration procedure), for example. 

Another synthetic route to 3-methylhasubanan (43), proposed by Lattes et al. (74), consists of the intramolecular aminomercuration (75) of amino-ethylphenanthrene 27. The key intermediate 27 was treated with mercury(II) acetate in THF/water to yield 9-acetoxymercury-3-methoxyhasubanan (46), as depicted in Scheme 3, and then the reaction product 46 was successively treated with benzyltriethylammonium chloride, sodium hydroxide, and sodium borohydride to furnish the target, 3-methylhasubanan (43) (74). 

The ratio of the two products is primarily affected by the nature of the mercury(II) salt and also by the reaction conditions. Since the formation of these compounds could result from either a kinetically or a thermodynamically controlled mercuration process, a study of the mercuration of 3 in the presence of aromatic amines using various mer-cury(II) salts has been more recently carried out in order to determine the conditions under which aminomercuration is reversible, and the results have been compared to those of the oxymercuration170. 

It is noteworthy that a complete stereoselectivity toward the cA-isomer, which is opposite to that found in aminomercuration of the same dienes173 characterizes these reactions. The following mechanism has therefore been proposed to rationalize the stereochemical behavior. After the addition to one of the double bonds, the electron pair of the nitrogen should interact with the mercury atom. In a second step, another mercury(II) ion from an additional molecule of mercury(II) nitrate is similarly complexed by the electrons of the nitrogen atom, requiring an approach from that same side and resulting in a cis... 

The preliminary electronic interaction seems to be required since, if the first mercury atom is absent, a trans addition takes place. Furthermore, a possible important role of the basicity of the nitrogen has been underlined taking into account that aminomercuration of 1,4- and 1,5-hexadienes with aromatic amines leads mainly to the trans isomer. 

Amino-5 -Chlorotoluene Aminocyclohexane Aminoethane 2-Aminoethanol Beta-Aminoethyl Alcohol 2-((2-Aminoethyl) Amino)Ethanol N-(2-Aminoethyl)Ethanolamine Aminoethylethanolamine Aininofonn 2-Aminoisobutane Aminomercuric Chloride Aminomethane... 

Hg(OAc)2 and Hg(OOCCFj)2 are the most frequently used reagents. Water and alcohols are the most common nucleophiles, and these processes are termed oxy-mercuration. Other additions are aminomercuration and peroxymercuration. 

Aminomercuration aminoalditols The synthesis of the natural aza-alditol 1-deoxynojirimycin (4) from methyl a-D-glucopyranoside involves the reductive ring-opening (Zn) and reductive amination (NaBH3CN) of 1 to give 2 in 91% yield. Aminomercuration of 2 results mainly in the bromomercurial 3, which was converted into the aza-sugar 4 by reductive oxygenation and deprotection. 

Alkoxysulfenylation Dimethyl(methylthiosulfonium) tetra-fluoroborate, 121 Aminomercuration Mercury(II) trifluoroacetate, 175 Azaselenylation Benzeneselenenyl halides, 26 N-Phenylselenophthalimide, 245 Azasulfenylation... 

Dimethylformamide dimethyl acetal, 120 Trisdimethylaminome thane, 121 Aminomercuration (see Addition reactions to carbon-carbon multiple bonds)... 

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. 

There do not appear to be any direct approaches for electrophilic addition of amines across C—C double or triple bonds. However, aminomercuration-demercuration affords a very useful process to effect this transformation (equation 151). This reaction has been thoroughly reviewed recently.194... 

Most work on aminomercuration has employed secondary aliphatic amines, or primary or secondary anilines. Primary amines have been successfully employed using mercuric perchlorate or mercuric nitrate.197 No reactions utilizing ammonia have been reported. While excess amine or various ether solvents can be used, it is sometimes desireable to add water.198 199... 

A wide variety of alkenes have been shown to undergo aminomercuration-demercuration, including alkenes bearing alcohol, ester, acid, amide, imide, urea, urethane, ether, sulfide and aryl groups.194... 

Although Markovnikov addition is generally observed, little woik on the regio- or stereo-selectivity of this reaction has been reported. Both cis- and franr-2-pentene afford mixtures of the 2- and 3-substituted amines.199 a.p-Unsaturated esters yield 3-amino esters.200 The aminomercuration of cis- and trans-2-butenes gives S 97% of the anti adducts.201... 

Bicyclic206 and spirocyclic207 amines are also readily prepared by intramolecular aminomercuration-demercuration (equations 153 and 154). 

Analogous cyclic amines can also be prepared by aminomercuration-demercuration of unsaturated organic halides (equation 155).208... 

Nonconjugated dienes also undergo aminomercuration-demercuration to generate pyrrolidines, piperidines and their heterocyclic analogs (equations 156-158).211-2,8... 

Allylic amines are usually obtained from the aminomercuration of allenes (equation 161),204221 while allenes with amino groups in a side chain produce the corresponding heterocycles (equation 162)222... 

The aminomercuration-demercuration of alkynes affords a variety of nitrogen-containing products. Most commonly imines are formed,194 though there are a few examples of enamines being produced (equation 163).223-228... 

Most cyclizations to form five-membered rings involve the 5-exo mode of cyclization. An exception has been reported in the intramolecular sulfenoamination of 3-alkenylamines used in the synthesis of pyrrolidine alkaloids (equation 102).215 229 Other examples include the aminomercurations of Af-sub-stituted-l-amino-3-butenes162,23° and the methylsulfenilium ion-initiated cyclization of 0-(2-propenyl)-/V-tosylaniline 231... 

In contrast, cyclizations of /V-alkoxy derivatives with iodine are much less selective (Table 30, entry 3), and similar results are observed with systems containing internal double bonds of either ( )- or (Z)-configuration.238 The stereoselectivity of the aminomercuration reaction of /V-methyl derivatives has been reported to be controlled by the choice of mercury(II) salt and solvent (entries 6 and 7).244 Cyclization with platinum salts showed little selectivity (entry 8).239 An iodocyclization of a complex N-alkyl system has been used in a recent synthesis of (+)-croomine.238... 

Few examples of stereoselectivity in 6-exo cyclizations to piperidine derivatives have been reported. The aminocarbonylation reactions of systems with an allylic hydroxy substituent that are quite stereoselective in cyclization to pyrrolidine systems (equation 106) are nonselective in cyclizations to piperidine systems.237 Cyclizations with mercury(II) acetate also proceed with low selectivity (59-69% cis isomer).237 A series of aminoalditols have been synthesized by aminomercuration of oxygen-substituted 6-(/V-benzylamino)hexenes. The stereochemistry of these cyclizations (equation 112)247 does not appear... 

Related intramolecular aminomercurations of cyclic guanidine derivatives have been studied in some detail,2 0 but are primarily useful for the synthesis of bicyclic heterocycles (equations 127 and 128). Cy-clizations of allylic isothiouronium salts have also been reported (equation 129).260b,260e... 

Some synthetically useful reactions not covered in the above sections should be mentioned. An unusual heterocyclization to form indole derivatives is found in the aminomercuration of allylenaminones (equation 130).261 Palladium(II)-catalyzed cyclizations of o-allyl- and -vinyl-anilines and amino-quinones are discussed elsewhere.30 Other electrophiles used to form dihydroindole derivatives include phenylselenenyl chloride216 and methyl(bismethylthio)sulfonium salts.231... 

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