Regioselective palladium-catalyzed formate reduction of N-heterocyclic allylic acetates

The regioselective palladium-catalyzed formate reduction of allylic acetates in five- to eight-membered heterocycles is reported. Reduction of allylic acetates under mild conditions using allylpalladium chloride dimer, phosphines, and formic acid/triethylamine in DMF gives the exo-cyclic olefins in good regioselectivities and high yields. Synthetic application in preparing N-tosyl-3-oxo-piperidine is also reported.     

Diastereoselective palladium-catalyzed formate reduction of allylic carbonates en route to polypropionate systems

Diastereoselective palladium-catalyzed formate reduction of allylic carbonates presents unique opportunities for applications in target-oriented organic synthesis provided that selectivity, in particular stereoselectivity, in the course of this metal-catalyzed reaction can be controlled. This article describes our recent developments on new and efficient metal-catalyzed processes exploiting resident stereocenters on the substrates as a means to control stereoselectivity en route to preparing propionate units containing an array of stereochemical patterns. In particular, the effect of the protecting group, the stereochemistry of the aldol adduct, neighboring substituents, and the olefin geometry were examined. Strategic choice of the above parameters provides entry into three of the four possible diastereomeric triads, namely syn-syn, anti-syn, and anti-anti. Preliminary results indicate that construction of the syn-anti triad is possible, albeit in moderate diastereoselectivity.     

Diastereoselective palladium-catalyzed formate reduction of allylic carbonates as a new entry into propionate units

[reaction: see text] The diastereoselective palladium-catalyzed formate reduction of allylic carbonates is described. Reduction of allylic carbonates under mild conditions (Pd(OAc)(2) (2.5-5 mol %), [n-Bu(3)PH]BF(4) (2.5-5 mol %), HCO(2)H/Et(3)N (1:2) (3 equiv), CH(3)CN (0.05M), 40 degrees C) affords the terminal olefin as the syn isomer in good yields and modest to excellent diastereoselectivity. These compounds, which are useful building blocks for the synthesis of polypropionate units, are the synthetic equivalent of the products obtained from an aldol reaction of an alpha-methyl-beta,gamma-unsaturated aldehyde.     

The acute toxicity of tri-n-butyltin glycocholate

The oral acute toxicity for tri-n-butyltin glycocholate (TBT-GA), a newly synthesized organotin steroid, was determined using Long Evans rats. The compound was suspended in corn oil and adminstered by gavage using standard techniques. Unlike tri-n-butyltin taurocholate, which exhibited two different toxicities, one for the tri-n-butyltin moiety and one for the taurocholic acid moiety, the TBT-GA exhibited a single toxicity, that of the whole molecule. The LD₅₀ value was 213 mg kg^?1 (0.274 mmol kg), which on a millimolar basis is similar to that observed for other tri-n-butyltin compounds. The dead rats exhibited distended stomachs, enlarged ceca, and lesions in the intestinal tract. The actual cause of death could not be positively identified. Animals that survived more than three days also exhibited time- and dose-related atrophy of the thymus gland. With 36% more male than female rats succumbing to TBT-GA, the chemical appears to be more toxic towards male than female rats.     

The acute toxicity of tri-n-butyltin taurocholate

The acute toxicity for tri-n-butyltin taurocholate (TBT-TA), a newly synthesized organotin steroid, was determined using Long Evans rats. The organotin compound was suspended in corn oil and administered by gavage using standard techniques. The TBT-TA exhibited a taurocholic acid toxicity at 24 h and a tributyltin toxicity at three days. The LD₅₀ values were 611 and 384 mg kg^?1 respectively. The dead rats exhibited distended stomachs, enlarged cecums, and lesions in the gastrointestinal tract. The toxicity is similar to that observed with other trialkyltin compounds.     

Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.     

Biodegradation of bis(tri-n-butyltin) oxide

Bis(tri-n-butyltin) oxide can be biodegraded by a mixed bacterial culture from activated sludge in cyclone fermentors under aerobic and anaerobic conditions with half-lives of five and three days respectively. The degradation follows a sequential dealkylation process. All the intermediates and end products are determined in the degradation process for mass balance calculation. Degradation under different nutrient conditions has been investigated. Adsorption losses for each of the butyltin and inorganic tin species on container walls have also been assessed and discussed.     

Palladium-catalyzed regio- and stereoselective formate reduction of fluorine-containing allylic mesylates. A new entry for the construction of a tertiary carbon attached with a fluoroalkyl group

The regioselective palladium-catalyzed formate reduction of gamma-fluoroalkylated allylic esters is described. Reduction of the allylic esters under the influence of palladium with a monodentate phosphine ligand proceeded preferentially at the gamma position, the corresponding reduction products with a fluoroalkyl group at the tertiary carbon being afforded in high yields. When the chiral allylic ester was employed, complete chirality transfer was observed, leading to the optically active materials in high yields.     

Iridium complex-catalyzed allylic amination of allylic esters

Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.     

Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines

[reaction: see text] A useful method for the conversion of prochiral allylic alcohols to chiral allylic amines of high enantiopurity is reported. N-(4-Methoxyphenyl)trifluoroacetimidates are excellent substrates for the palladium(II)-catalyzed allylic imidate rearrangement as the allylic trifluoroacetamide products can be deprotected in two steps to provide chiral nonracemic allylic amines. Di-mu-chlorobis[(eta(5)-(S)-(pR)-2-(2'-(4'-isopropyl))oxazolinylcyclopentadienyl,1-C,3'-N))(eta(4)-tetraphenylcyclobutadiene)cobalt]dipalladium (6a, COP-Cl) is a superior catalyst because it does not require activation with silver salts and provides rearranged allylic trifluoroacetamides in good yields and high enantiomeric purities.     

Studies of the polarity of the tri-n-butyltin radical

A satisfactory Hammett correlation was observed for the radical reduction of substituted benzyl halides by tri-n-butyltin hydride. The magnitude of the positive ? value comparable to that observed for other nucleophilic radicals.     

Synthesis of tri-n-butyltin taurocholate,taurodeoxycholate and glycocholate

The bile acids, taurocholic, taurodeoxycholic and glycocholic acid, were reacted with bis(tri-n-butyltin) oxide (TBTO) to form 1:1 derivatives. The water of reaction was removed with 2, 2-dimethoxypropane or by azeotropic distillation with benzene. The compounds were characterized by ¹³C and ¹¹⁹Sn NMR, IR, elemental analysis, molecular weight determination, DTA, TGA, and conductance measurements. The data indicated that tri-n-butyltin glycocholate forms a covalent ester, tin being tetracoordinated. The taurocholic and taurodeoxycholic acid derivatives contain one molecule of coordinated water. They partially dissociate in polar solvents. The taurocholic and glycocholic acid derivatives were tested in vitro as anticancer agents and exhibited ED₅₀ in the 0.2–0.4 ppm (mg kg^?1) range against KB epidermoid tumor and P-388 leukemia using NCI protocols.     

The free-radical reaction of tri-n-butyltin hydride with disulfides

The kinetics and absolute rate constants for the free-radical chain reaction of tri-n-butyltin hydride with di-t-butyl disulfide have been measured in cyclohexane at 30°. The rate controlling step for chain propagation involves the cleavage of the disulfide bond by an attacking tributyltin radical. The rate constant for this bimolecular homolytic substitution at sulfur is ～8 × 10⁴ Mole^?1 sec^?1. Chain termination involves the self-reaction of two tributyltin radicals. The rate constants for attack of tributyltin radicals on some other disulfides and on elemental sulfur have also been measured. The results are compared with literature data for homolytic substitutions on these compounds by a variety of radicals which have their unpaired electron centered on carbon.     

The free-radical reaction of tri-n-butyltin hydride with peroxides

Rate constants for the tri-n-butyltin radical ( Sn · ) induced decomposition of a number of peroxides have been measured in benzene at 10°C. The values range from ～100 M^?1 sec^?1 for di-t-butyl peroxide to 2.6 × 10⁷ M^?1 sec^?1 for di-t-butyl diperoxyisophthalate. The majority of the peroxides, including diethyl peroxide, diacetyl peroxide, and t-butyl peracetate, have rate constants of ～10⁵ M^?1 sec^?1. It is shown that di-n-alkyl disulfides are ten times as reactive toward Sn · as di-n-alkyl peroxides, although the exothermicities of these reactions are ～15 and ～39 kcal/mole, respectively. The enhanced reactivity of the disulfides is attributed to the easier formation of an intermediate or transition state with 9 electrons around sulfur, compared with an analogous species with 9 electrons around oxygen. The following bond strengths (kcal/mole) have been estimated: D[ Sn ? OR] = 77; D[ Sn ? H] = 82; D[ Sn ? SR] = 83; and D[ Sn ? OC(O)R] = 86, where R = alkyl. Rate constants for reaction of Sn · with some benzyl esters have also been measured. It has been found that t-butoxy radicals can add to benzene and abstract hydrogen from benzene at ambient temperatures.     

Ruthenium complex-catalyzed allylic alkylation of carbonucleophiles with allylic carbonates

Allylic carbonates except for allyl methyl carbonate reacted with carbonucleophiles such as ethyl acetoacetate in the presence of a catalytic amount of Ru(cod)(cot) [cod = cycloocta-1,5-diene, COT = cycloocta-1,3,5-triene] in N-methylpiperidine at 80°C to give the corresponding monoallylated carbonucleophiles in high yields with high regioselectivity. The regioselectivity was quite different from that in the palladium-catalyzed reactions. The allylation of carbonucleophiles using allyl methyl carbonate selectively gave the diallylated carbonucleophiles in high yields.     

醋酸烯丙酯选择性地合成烯丙基硒醚

醋酸烯丙酯被Pd(PPh3)4-SmI2还原，并发生中间体π-烯丙基钯络合物的极性 反转，而后与芳基硒溴化物作用，生成烯丙基硒醚．     

The diastereospecific aprotic conjugate addition reactions of carbanions derived from allylic sulfoxides and allylic phosphine oxides.

The title carbanions undergo conjugate addition to cyclic enones in THF to deliver vinylic sulfoxides and vinylic phosphine oxides as single diastereomers.