Aminomercuration-demercuration

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... 

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... 

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... 

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... 

The addition of amines to electrophilic alkynes and allenes to give enamines is well known221222. It is possible to prepare the F-isomer in a pure state by a stereospecific addition of an amine to an alkyne (equation 10). Enamines have also been obtained by an aminomercuration-demercuration sequence involving addition of aromatic amines to the substituted carbon of unactivated terminal acetylenes 223-225 (equation 11). 

The action of mercury(ll) acetate on 165 in a THF solution followed by demercuration with an alkaline solution of sodium borohydride, gave a substituted 3-silapyrrolidine 166 in 58% yield. Analogously, under the same conditions of aminomercuration-demercuration, allyl(phenylaminomethyl)dimethylsilane 167 easily formed C-methyl-substituted five-membered heterocycle 43 (Equation 29). 

The same reaction sequence as employed for the conversion of 101 to 103 was applied to ent-101 to give tetracycle ent-103 in 18% yield (two steps) (Scheme 22). Alternatively, Wittig reaction of ent-101 with Ph3P=CHI afforded vinyl iodide 108 in better yield (72%, E Z = 1 2). The Heck reaction of 108, however, resulted in the formation of ent-103 with lower yield (31%) than that of ent-102. The attempted new procedure via vinyl iodide 108 slightly improved the overall yield of ent-103 from ent-101 (22% for two steps). Inversion of the C-6 hydroxy group and deprotection of IV-Boc group gave methylamine 81. Aminomercuration/ demercuration of 81 provided (-)-codeine in 24% yield. 

The aminomercuration-demercuration reaction has provided two examples for primary to secondary amine conversion.In one, Markovnikov addition of the aminomercurial (10) to an alkene, followed by ligand exchange with sodium hydroxide and subsequent reduction with sodium borohydride, yields the secondary amine (11) in a one-pot reaction (Scheme 10). In the other,vicinal diamines (12) are the products from the one-pot reaction of alkenes with tetrafluoroboric acid and mercury(ll) oxide in the presence of excess primary amine (Scheme 11). Both reactions work equally well with secondary amines. 

New syntheses of 1,2-alkanediamines from imidazolin-2-ones via photochemical cycloaddition, from 2-ethyl-4,5-dihydro-l,3-oxazole, a new aziridine equivalent, and from allylamines via aminomercuration-demercuration have been reported. 

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