Cyclization mercury-induced

The mercury-induced cyclization of the (T )-enol ether (E)-5 is less stereoselective and a 70 30 (a// ) diastereomeric mixture, as determined by HPLC, is obtained. This result has been explained as being due to both the structure of the mercurinium ion and the anomeric effect94. 

The intramolecular mercury-induced cyclization of enol ethers has proven useful for the dia-stereoselective preparation of disaccharides. The reaction is carried out by treating the enol ethers (e.g., 7) with mercury(ll) trifluoroacetate in tetrahydrofuran for 2 hours at 0 °C, followed by reaction with aqueous potassium chloride at 0 °C for 1 hour. The chloromercury derivatives are obtained in good yield and only one isomer can be detected in the reaction mixture95-96. 

Mercury-induced cyclization of 1-substituted 4-pentenylamines afforded 2,5-disubstituted pyrrolidines with high 1,3-asymmetric induction, the stereochemical outcome of the cyclization is determined by the reaction conditions75, 76. Treatment with mercury(II) chloride in tetrahy-drofuran/watcr (kinetic conditions) gave the iran.v-isomer as the major isomer in the reaction mixture. However, when mercury(ll) chloride in chloroform or mercury(II) chloride in tetrahy-drofuran were employed as electrophiles (thermodynamic conditions), the more stable s-iso-mer was obtained as the predominant component of the reaction mixture this result can be ascribed to a double A1 2 interaction76. 

In addition, the mercury-induced cyclization of the derivatives 2 gave 3 with moderate yield and poor stereoselectivity the configuration of the products was assigned by HNMR 225. 

Pyrrolizidines 1 were obtained with high stereocontrol (100% tram addition) by intramolecular cyclization of l-aza-4-cyclooctene with phenylsulfenyl or phenylselenenyl halides. Analogous results were also obtained by the mercury-induced cyclization performed with mercury(II) chloride in tetrahydrofuran113. 

Evidence for kinetic control as opposed to thermodynamic control results from the comparison of the mercury-induced cyclization of. V./V-diallyla ni lines and JV-allylcarbamate. When A1, A -dial lylanilines were treated with mercury(II) acetate in tetrahydrofuran (kinetic control), trnns-WV-diary I-2,5-dimethyl piperazines 2 were stereoselectively prepared in good yield. Formation of the less stable Pv2rt.y-2,6-dimcthyl derivative is a result of kinetic control of the cyclization124. 

Intramolecular mercury-induced cyclization of A -allvlcarbamate with mercury(II) nitrate in dichloromethane proceeded under thermodynamic control and gave after reductive cleavage the more stable diethyl m-2.5-dimethyl-1,4-piperazinedicarboxylate (3), exclusively, in 98 % yield124... 

The mercury-induced cyclization of amidals derived from secondary homoallylic alcohols afforded only six-membered ring products 7 via a 6-exo mode. For short periods (under kinetic control) the fa-isomer was the major product, while for longer periods (under thermodynamic control) the trans-isomer was formed with very high stereoselectivity161,162. 

The mercury-induced cyclization of amidals in which a stereogenic center is positioned at the amidal center adjacent to the nucleophilic amide functionality, gave oxazolidines with high stereoselectivity. Reaction of the amidals 10 with mercury(ll) acetate/mercury(ll) trifluoroac-etate in acetonitrile in the presence of sodium hydrogen carbonate followed by reductive cleavage with sodium borohydride afforded the corresponding fused oxazolidines 11164. 

When amidals obtained from secondary allylic alcohols are cyclized with mercury(ll) acetate or mercury(II) acetate and trifluoroacetic acid, the corresponding 4,5-disubstituted oxazoli-dines 12 and 13 are formed. The 1,3-asymmetric induction overrides the competing 1,2-asymmet-ric induction of the allylic substituent. When the tram-isomers 12 were formed, only one diastereomer was obtained. However, when steric interactions between the substituents are low, m-diastereomers were predominantly obtained, e.g., 13, although the amount of the nans-diastereomcrs increases on increasing the bulkiness of the allylic substituent. As the oxazolid-ines obtained by mercury-induced cyclization of the amidals are easily cleaved to amino alcohols with hydrazine, this approach allows either a syn- or vicinal amino alcohol to be obtained starting from a single secondary allylic alcohol. 

Perhaps, however, aminocyclitol derivatives are the most important group of compounds to have become accessible by application of the mercury-induced reaction, since they figure prominently in natural products - notably the aminoglycoside antibiotics. Central to many of these are compounds 25 (strepti-dine) and 26 (2-deoxystreptamine) that occur in glycosylated forms in streptomycin and the neomycins, respectively, and compounds of this type have frequently been made by the mercury-based cyclization procedure. The amino... 

Substrate-controlled, mercury-induced formation of a tetrahydropyran-ring was employed by Evans in the stereoselective cyclization of hydroxy olefin 232 (Scheme 9.31) [171]. The high selectivity was attributed to transition state structure 233, in which Aj 3-like interactions are minimized. The cy-clized product 234 (99% yield) served as a key intermediate in the total synthesis of the polyether antibiotic X-206 (235). 

Cyclization induced by mercuric ion is often used in multistep syntheses to form five- and six-membered hetereocyclic rings, as illustrated in Scheme 4.6. The reactions in Entries 1 to 3 involve acyclic reactants that cyclize to give exo-5 products. Entry 4 is an exo-6 cyclization. In Entries 1 and 2, the mercury is removed reductively, but in Entries 3 and 4 a hydroxy group is introduced in the presence of oxygen. Inclusion of triethylboron in the reduction has been found to improve yields (Entry l).113... 

Trichloroacetimidates derived from tetrahydrofuran homopropargyl alcohols were cyclized by mercury(ll) trifluoro-acetate-induced hydroamination to the corresponding 5,6-dihydro-4/7-l,3-oxazine derivatives with excellent stereoselectivity <1998CC761>. 

In addition, 1,3-dioxanes have been prepared by mercury salt-induced cyclization of 1-hydroxyallylphosphonates with propionaldehyde (Equation 84). The Hg was subsequently removed from the heterocycle with cyanoboro-hydride <2002PS1583>. 

Mercury(II) oxide and acetic acid effect the cyclization of l,4-diaryloxybut-2-ynes to 4-aryloxymethylchromenes. The transformation was attributed to cyclization of the butanone which resulted from hydration of the alkyne (72JHC489). However, it has since been shown that similar butanones do not cyclize to chromenes under the cyclization conditions (78JOC3856). Instead, a mechanism is proposed which involves a charge-induced Claisen rearrangement which is triggered by 7r-complex formation between the metal ion... 

Langer also prepared other functionalized 2-alkylidenetetrahydrofurans by cyclization of l,3-fc(trimethylsiloxy)- 1,3-butadienes with epoxides <02CEJ1443>. Mercury(II)-induced cyclization of the hydroxyalkyne below led to the formation of the enol ether <02TL3011>. 

Several cases have been reported in which the reactivity of the C-C douhle hond towards nucleophilic attack is further enhanced by an external electrophile. An example of an exo-trig cyclization induced by mercuration is shown in the case of the unsaturated acid rac-1 which was converted to the cyclic acetals (otR,2S)-2 and (y.S.2S)-2 employing mercury(ii) acetate in methanol followed by subsequent demercuration40. In the latter step, sodium trithiocarbonate afforded the highest selectivity in terms of retention of configuration (cf. Section 4.7.1.1.1.1.2.). 

The cyclization of 1-substituted 5-alkenylamines promoted by mercury(II) salts gave piperidines 1 with moderate induced diastereoselectivity after reductive cleavage103. 

Mercury(II) induced cyclization of jV-benzyloxycarbonyl-6-hepten-2-aminc gave a 2,6-disubsti-tuted piperidine derivative 3. Depending on whether the reaction conditions result in kinetic or thermodynamic control of the products, moderate to total stereoselectivity was obtained. While kinetic conditions [mercury(II) acetate in tetrahydrofuran] gave 3 with a d.r. trans/cis 60 40, under equilibrating conditions [mercury(ll) trifluoroacetate in nitromethane] the d.v-2,6-isomcr was essentially the sole product [d.r. (cis/trans) 98 2], Thus the initial cyclofunctionalization of the carbamate is not highly stereoselective, but under conditions favoring equilibration, conversion of the fra/iy-isomer into the more stable cu-isomer occurs82,105. 

The mercury(II)-induced cyclization of the m-2,6-disubstituted piperidine 10, prepared by selenium-induced cyclization of the unsaturated 0-benzyl oxime followed by reduction of the intermediate cyclic iminium salt251 (Section 7.2.6.2.6.), occurred efficiently and diastereoselectively (NOE). 

Transannular cyclization of unsaturated lactams was induced by mercury(ll) acetate, the weakly nucleophilic amidic nitrogen is the reaction center. The driving force for this cyclization is the strain of the bicyclic product, only one isomer was recovered regardless of the alkyl substituent. By reductive cleavage the bicyclic lactam, e.g., 6, was obtained in moderate to good yield125. 

Dihydrooxazoles were also obtained by cyclization of imidates induced by mercury salts. Thus, treatment of an allylic alcohol with dimethylcyanamide in the presence of sodium hydride gave the corresponding imidate 9 in 90% yield. Subsequent cyclization, performed in tetrahy-drofuran with mercury(II) trifluoroacetate followed by cleavage with sodium borohydride, gave a single enantiomer of the 4,5-dihydrooxazole 10 in 80% yield157. 

Chiral imines obtained from a-phenylethylamine have been used with some success for asymmetric induction in cycloadditions with enolates. Addition of the tin enolate obtained by addition of tin(II) chloride to the lithium enolate of the thioester 7 to imine 8 followed by treatment with mercury(II) bis(trifluoracetate) to induce cyclization affords a 91 9 mixture of cis- and fram-j8-lactams 9. The cw-/ -lactam 9 is obtained with d.r. [(2S,3S)/(2R,3R)] 85 1584. 

A more recent application of a similar cyclization is during a synthesis of (+)-preussin 230 in which a key step is mercury(II)-induced cyclization of the ynone 228 to give the keto-dihydropyrrole 229 <94JOC4721>. There are a number of notable features of this reaction. Firstly, despite conjugation to the keto group, the alkyne remains sufficiently nucleophilic to interact with the electrophilic mercury, the intermediate ketone is stable to racemization and the Af-Boc group does not interfere, presumably because the 5-endo-dig mode is favoured. 

Baiyunoside (1) is the sweet principle of a Chinese drug Phlontis hetonicoides (Labiatae).2 Through mercury (11) triflate induced biomimetic olefin cyclization followed by... 

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