The synthesis and cyclisation of thioacylated diaminoguanidines

The thiobenzoylation of 1,2-diaminoguanidine yields 1-amino-2-thioaroylamidoguanidines which are isolable as their stable hydrazones. They are unaffected by alkalis, but are cyclised by mineral acids, with loss of ammonia, to hydrazones of 2-aryl-5-hydrazino-1,3,4-thiadiazoles, or with elimination of hydrazine, to the appropriate 2-amino-5-aryl-1,3,4-thiadiazoles. The action of acetic anhydride effects the same ring-closures, yielding the corresponding acetylated products. 1,2-Diamino-3-phenylguanidine undergoes a comparable series of reactions.     

Stereochemistry of cyclic ether formation—II : Intramolecular cyclisation of secondary aliphatic alcohols to tetrahydrofuran-type ethers

The mechanism and stereochemistry of δ-C atom functionalisation in the reactions of secondary straight-chain aliphatic alcohols with lead tetraacetate, ceric ammonium nitrate, and heavy metal (Pb⁴⁺, Hg²⁺, Ag⁺) salts (AcO)^?1, O^2?, CO₃^2?-halogen (I₂, Br₂, Cl₂) combinations are discussed. By demonstrating the intermediacy of 5-bromo-2-hexanol, it was confirmed that the dark silver oxidebromine induced cyclisation of 2-hexanol (and alcohols in general) involves (as the other hypohalite reactions) intramolecular 1,5-hydrogen abstraction by alkoxy radicals and formation of δ-bromohydrins. A novel and simple procedure for obtaining tetrahydrofurans from alcohols by way of the hypochlorite reaction, using silver or mercuric salts and chlorine, is described.     

Stereochemistry and mechanism of acylation of acetylenes

The addition of acid chloride-AlCl₃ complexes and of acyl triflates to several acetylenes has been performed. Evidence is given that these additions occur at least partly through a vinyl cation intermediate. In the case of aroyl chlorides or aroyl triflates the intermediate vinyl cation can be attacked by the aromatic nucleus of the aroyl group, leading to the formation of indenones. The difference in behaviour between aroyl chloride-AlCl₃ complexes and aroyl triflates is explained by the hardness of the triflate anion as a nucleophile, compared to the tetrachloraluminate anion. Further evidence for the intermediate vinyl cation is found in the formation of rearranged products in the addition of 3,5 dimethoxybenzoyl chloride-AlCl₃ complex and benzoyl triflate to 4,4-dimethyl-2-pentyne.     

Stereoselective synthesis of tarchonanthuslactone via the Prins cyclisation

The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step.     

Cyclic sulfonimidates by dynamic diastereomer-differentiating cyclisation: large-scale synthesis and mechanistic studies

A dynamic diastereomer differentiating cyclisation is the key step in a new large-scale synthesis of both enantiomers of the cyclic sulfonimidates 1 (Aldrich no. 54099-4) and ent-1 (Aldrich no. 54412-4). These are valuable starting materials in the asymmetric synthesis of chiral oxa- and azaheterocyclic compounds. NMR spectroscopic studies on the reacting system reveal N-chloro sulfinamides to be reactive intermediates in the oxidative chlorination of sulfinamides with tert-butyl hypochlorite and allow for the inspection of the configurational behaviour of the involved sulfonimidoyl chlorides and sulfonimidoyl bromides.     

Stereoselective synthesis of simplactone B via Prins cyclisation

The synthesis of simplactone B has been achieved through a series of nine steps in 85% overall yield using Prins cyclisation as the key step with high stereochemical control.     

Stereochemistry and mechanism of a microbial phenylalanine aminomutase

The stereochemistry of a phenylalanine aminomutase (PAM) on the andrimid biosynthetic pathway in Pantoea agglomerans (Pa) is reported. PaPAM is a member of the 4-methylidene-1H-imidazol-5(4H)-one (MIO)-dependent family of catalysts and isomerizes (2S)-α-phenylalanine to (3S)-β-phenylalanine, which is the enantiomer of the product made by the mechanistically similar aminomutase TcPAM from Taxus plants. The NH(2) and pro-(3S) hydrogen groups at C(α) and C(β), respectively, of the substrate are removed and interchanged completely intramolecularly with inversion of configuration at the migration centers to form β-phenylalanine. This is a contrast to the retention of configuration mechanism followed by TcPAM.     

Stereoselective synthesis of basiliskamides A and B via Prins cyclisation

A stereoselective and convergent approach to basiliskamides A and B is achieved through our recently developed strategy for the construction of polyketide precursors via Prins cyclisation. The approach mainly relies upon reductive opening of 1-iodomethyl cyclic ethers, Mitsunobu inversion, Takai olefination and Stille coupling along with Prins cyclisation.     

Stereochemistry in the synthesis and reaction of exo-glycals

Two general methods are explored for the stereoselective synthesis of exo-glycals. One method utilizes a nucleophilic addition of fully protected sugar lactones of gluco-, galacto-, and manno-types, followed by the subsequent dehydration, to give the desired exo-glycals with (Z)-configuration. The other method proceeds with selenylation of C-glycosides in a stereoselective manner. The subsequent selenoxide elimination also provides (Z)-exo-glycals. The prepared exo-glycal conjugated esters of either gluco- or manno-type react with allyl alcohol to give exclusively alpha-anomers.     

Stereochemistry of heterocycles. XL. Stereochemistry of the synthesis of 2,3-dialkyloxetanes

It is shown that trans-2,3-dialkyloxetanes are formed from the erythro isomers of 2-alkyl-1,3-butanediols, whereas cis-2,3-dialkyloxetanes are formed from the threo isomers.See [1] for communication XXXIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 164–168, February, 1976.     

A novel synthesis of tetrahydrofuran via alkoxy radical cyclisation

Tetrahydrofurans were synthesised via 5-exo-trig cyclisation of alkoxy radical generated by unprecedented 1,5-hydrogen shift from hydroxyl group to vinyl radical.     

Stereochemistry and mechanism of catalytic hydrogenation of substituted methylenecyclohexanes

Substituted alkylmethylenecyclohexanes were hydrogenated over several transition metal catalysts. The ratios of the epimeric products were almost unity over freshly prepared Raney Ni but the axial Me counterparts were favoured over aged catalyst. The axial Me products were also preferred on Pt or Rh catalysts. Pd catalysed hydrogenation gave predominantly the equatorial Me isomers at high catalyst ratio, while the axial Me counterparts were favoured at the early stage of the reaction at a catalyst-substrate ratio of 1:20. The change of the ratio of epimeric products depending on the amount of catalyst is due to the rapid migration of exo-cyclic double bond to the inside of the cyclohexane ring at high catalyst ratio. The mechanism of hydrogenation is discussed in terms of the modified Horiuti-Polanyi mechanism.     

Stereochemistry and mechanism of catalytic hydrogenation of substituted cyclohexanones

Substituted alkylcyclohexanones were hydrogenated over several transition metal catalysts. The hydrogenation with freshly prepared Raney Ni gave predominantly the axial alcohols but catalyst to which sodium hydroxide was added or aged catalyst increased the stereoselectivity. In contrast to the PtO₂ hydrogenation in which the equatorial alcohols were favoured, more axial alcohols were obtained than the equatorial counterparts on Pt-black. On Pd catalyst the isomeric ratios of the cyclohexanols changed as the reaction progressed. This may be due to a decrease in the amount of hydrogen available caused by the strong adsorption of ketones on the catalyst. Rh catalyst gave more of the axial alcohols than any other catalyst used in the present study.     

Stereochemistry and mechanism of aikali metal reductions of cycloalkanones

Work on steroidal 16-ones has indicated that whereas the stereochemistry of reduction of cycloalkanones by alkali metals in ethanol is linked with the FMO picture of the corresponding ketyl ion pair, the reduction of enolizable ketones by K in anhydrous ammonia is controlled by steric factors connected with proton abstraction by a dianion from alpha to a ketone.     

Stereochemistry and mechanism of the hydrogenation of substituted cyclopentenes

1,2- and 2,3-disubstituted cyclopentenes were hydrogenated with several transition metal catalysts. The hydrogenation of 1,2-disubstituted cyclopentenes gave preferably the cis products with Raney Ni, whereas 2,3-disubstituted cyclopentenes gave preferably the trans isomers. The trans products were favoured in the hydrogenation of 1,2- and 2,3-dialkylcyclopentenes with Pt or Pd catalysts. A detailed product analysis of the hydrogenation of 1,2-dialkylcyclopentenes indicates that the double bond migration occurred to form 2,3-dialkylcyclopentenes in advance of the hydrogenation. In contrast, 1-methyl-2-phenylcyclopentene gave predominantly the cis product irrespective of the kind of catalyst. These results suggest the formation of a π-benzylic species during the course of the reaction. The mechanism is discussed in terms of the modified Horiuti-Polanyi mechanism.     

Studies in polyether synthesis: Spiroacetal formation by directed bisepoxide cyclisation.

The synthesis of tricyclic polyether fragments 15 and 20, which incorporate a spiroacetal subunit, using directed bisepoxide cyclisations is described.     

o-Bornylphenol: Stereochemistry and synthesis of new derivatives from its (+)-enantiomer

New derivatives of the (+)-enantiomer of o-bornylphenol were synthesized with a view to determine the configuration of chiral centers therein. The absolute configuration of the terpene substituents in the Mannich reaction product obtained from 4,13-diaza-18-crown-6 was estimated as (1R,2R,4S) on the basis of anomalous X-ray scattering.