Demercuration with sodium borohydride

Eq. 34). The resultant p-mercurioalkyl peroxides can often be demercurated with sodium borohydride (Eq. 35), or by brominolysis (Eq. 36) without substantial cleavage of the 0-0 bond. Both peroxymercuration and demercurations occur rapidly under mild conditions 48). 

Analogously, mixtures of A-alkoxycarbonyl- and iV-tosyl-9-azabicyclo 3.3.11- and [4.2.1]nonanes were obtained by reaction of 3 with carbamates or p-toluenesufonamide in the presence of mercury(II) nitrate followed by in situ demercuration with sodium borohydride (equation 168)171,172. 

Oxy-Cope rearrangement. Tertiary 1,5-hexadiene-3-ols undergo oxy-Cope rearrangement at room temperature on treatment with 1 equiv. of mercury(II) trifluoroacetate and subsequent demercuration with sodium borohydride.2 The corresponding secondary alcohols undergo polymerization in the presence of this salt. 

Conversion of synthetic picrotoxinin (1) to picrotin (2) was achieved by Corey and Pearce in four steps and 30% overall yield 124). To prevent intramolecular oxymercuration, the tertiary alcohol of picrotoxinin (1) was protected as trifluor-oacetate 346 prior to addition of mercury trifluoroacetate in a benzene/THF mixture as solvent. Demercuration with sodium borohydride failed, thus the covalent C-Hg bond was cleaved by tributylstannane in ethanol. Mild hydrolysis of the bistrifluor-oacetate 347 afforded picrotin (2) in 30% overall yield (75% corrected for recovered 1) from picrotoxinin (1). 

Phenyl-4-pentenoic acid (3) is converted to the corresponding mercury derivative 7 by treatment with mercury(II) acetate in methanol26. After demercuration with sodium borohydride in sodium hydroxide, dihydro-5-methyl-4-phenyl-2(3//)-furanone (8) is obtained as an 85 15 mixture of trans/cis-isomers in 45 % yield. 

Aminomercuration leads to substituted organomercurials 5.5, which also suffer demercuration with sodium borohydride, preferentially under PTC conditions [BEl, EB4] (Figure 5.5). The mechanism proposed for this reduction in protic solvents is an ionic one, implying the intermediate formation of aziridinium salt [L3]. This method has been applied to the synthesis of cyclic amines from a,P-ethyienic precursors 5.6 [EB4] (Figure 5.5). When the reduction in run in alcohol or water, mixtures of five- and six-membered cyclic amines are obtained from each precursor 5.6 (n = 1 or 2). 

The intramolecular addition of a hemiacetal hydroxy-group to a neighbouring double bond in the presence of mercuric salts can be used to effect regioselective hydration of the double bond. Thus treatment of (490) with chloral and mercuric trifluoracetate in dry THF, followed by demercuration with sodium borohydride, gave (491) in good yield. The trichloroacetal group may be removed by treatment with a sodium dispersion in dry ether or zinc in refluxing acetic acid. ... 

The well known valerolactone (115), commonly described as the Prelog-Djerassi lactone, has attracted the attention of many synthetic chemists over the years and another synthesis of this important macrolide antibiotic intermediate has appeared (Scheme 13). The synthesis involves the Hg -induced cycliz-ation of the aldehyde (114) to control the stereochemistry at C(2) and C(3). This was followed by demercuration with sodium trithiocarbonate in methanol at -60 C, hydrolysis, and oxidation to give the lactone (115) and its epimer in a 3.5 1 ratio. Demercuration with sodium borohydride followed by hydrolysis and oxidation gave almost complete inversion. 

Y. S. Shabarov, S. S. Mochalov, T. S. Oretskaya, and V. V. Karpova. Mercuration of some styrenes and phenylcyclopropanes. The effect of the aromatic nitro group on reductive demercuration with sodium borohydride. /. Organometallic Ghent., 1978, 150, 7. 

The technique of methoxymercuration-demercuration was utilized to determine the position of double bonds in the side chains. Since this method is not successful with the free alkaloids (272), the secondary amino groups must be protected as the A -heptafluorobutyramide. These amides are treated with mercuric acetate and methanol followed by reduction with sodium borohydride to yield the methoxylated compounds (273). The mass spectra of these compounds show a fragment ion (274) at m/z 59 indicating terminal double bonds in every case (Scheme 22) 16,25,410,411). 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

The adducts may be demercurated in situ, frequently with sodium borohydride or with a halogen ... 

Treatment of azido(2-azidocyclopropyl)mercury(II) derivatives with sodium borohydride under basic aqueous conditions led to concomitant C —Hg cleavage and C —H bond formation and formation of the corresponding azidocyclopropanes. Reductive demercuration also took place when (cw-2-azidocyclopropyl)bromomercury(II) derivatives were reacted with sodium amalgam and deuterium oxide mercury was replaced stereospecifically with deuterium leading to c -l-azido-2-deuteriocyclopropanes. The yields are generally very low (< 25%). 

Azasilacyclopentanes are most conveniently prepared by the amidomercuration-demercuration of dimethyl(chloroalkyl)alkenylsilanes of the form (131) <87JOM(326)i59,85ZOB706). Thus, treatment of dimethyl(chloromethyl)vinylsilane (Ola, n = 0) or dimethyl(chloromethyl)allylsilane (131b, n = 1) with aniline in THF in the presence of mercury acetate, followed by reduction with sodium borohydride, afforded the azasilacyclopentanes (Ola), (132b). 

Oxymercuration-Demercuration Alkenes react with mercuric acetate in a mixture of water and tetrahydrofuran (THF) to produce (hydroxyalkyl)mercury compounds. These can be reduced to alcohols with sodium borohydride and water (Section 8.5). 

In the oxymercuration step, water and mercuric acetate add to the double bond in the demercuration step, sodium borohydride reduces the acetoxymercury group and replaces it with hydrogen. The net addition of H — and —OH takes place with MaJ-kovnikov t oselectivity and generally takes place without the complication of rearrangements, as sometimes occurs with acid-catalyzed hydration of alkenes. The overall alkene hydration is not stereoselective because even though the oxymercuration step occurs with anti addition, the demercuration step is not stereoselective (radicals are thought to be involved), and hence a mixture of syn and anti products results. 

The methoxymercuration of 4,6-0-benzylidene-D-allal yielded isomeric acetoxy-mercurial adducts having the -D-allo (439) and a-D-altro (440) configurations. Demercuration of (439) with sodium borohydride gave methyl 4,6-0-benzylidene-2-deoxy-P-D-ri6o-hexopyranoside (72%), the ot,p-unsaturated aldehyde (441) (8.3 %), and a trace of the original glycal, while demercuration of (440) gave methyl 4,6-0-benzylidene-2-deoxy-a-D-r/6o-hexopyranoside (40%), (442) (23.5%), and traces of other products. 

Notice that the attack takes place at the more substituted position, ultimately leading to Markovnikov addition. After attack of the nucleophile, the mercury can be removed through a process called demercuration, which is generally accomplished with sodium borohydride. There... 

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. 

Mercury adducts can also be reacted with sodium borohydride and converted to methoxy compounds (oxymercuration-demercuration) [321,613], or reacted with halogens in methanol to form methoxyhalogen compounds [611], Such derivatives have been utilised for locating double bonds in fatty acids by mass spectrometry. 

In the laboratory, alkenes are often hydrated by the oxymercuration-demercuration procedure. Oxymercuration involves electrophilic addition of Hg2+ to the alkene on reaction with mercury(II) acetate [(CH3C02)2Hg, often abbreviated Hg(OAc)2] in aqueous tetrahydrofuran (THF) solvent. When the intermediate organomercury compound is then treated with sodium borohydride, NaBH4, demercuration occurs to produce an alcohol. For example ... 

Sfli Stereochemistry. Treatment of the 3-mercurated cyclic peroxides with sodium "Borohydride leads to mixtures of demercure ted cyclic peroxides and epoxy-alcohols. Thus, reacts to give the cyclic peroxides and the epoxy-alcohol in a 3 1 ratio. 

In the subsequent demercuration, the mercury-containing substituent is replaced by hydrogen through treatment with sodium borohydride in base. The net result is hydration of the... 

In an oxymercuration-demercuration reaction, an alkene is treated with mercury(II) acetate, Hg(OAc)2, and the product is treated with sodium borohydride. The net result is a Markovnikov addition product in which the OH group bonds to the more substituted carbon atom of the alkene. 

The reaction of alkoxymercurated adduct with sodium borohydride in shghtly basic solution results in demercuration and formation of the ether product. The regiospecificity of the addition follows Markovrukov s rule. 

Alkaline sodium borohydride is the preferred demercuration reagent, but sodium-mercury amalgam in D2O is best for stereospecific reduction with retention.268... 

The demercuration of these cyclic mercurials is fraught with more problems than analogous mercurials formed by intermolecular processes. Alkaline sodium borohydride is once again the most common reducing agent, but elimination to the starting unsaturated alcohol is not unusual. The extent of elimination varies with the mercury ligand, the pH and the solvent used.434 Phase transfer approaches offer advant-... 

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