Synthesis of versatile chiral intermediates by enantioselective conjugate addition of alkenyl Grignard reagents to enamides deriving from (R)-(−)- or (S)-(+)-2-aminobutan-1-ol

Conjugate addition of but-3-enylmagnesium bromide to the chiral crotonamide (R)-(+)- and (S)-(−)-3, followed by hydrolysis and oxidation, afforded enantiopure (R)-(+)- and (S)-(−)-3-methyladipic acids 8, respectively. Conjugate addition of vinylmagnesium chloride to the chiral crotonamide and cinnamamides (R)-(+)-3–5, followed by hydrolysis, gave the alkenoic acids (S)-12–14, respectively. Iodolactonization of the latter led to the 5-iodomethyllactones (+)-15–17, which were reduced by means of n-Bu₃SnH into the trans-disubstituted 5-methyllactones (+)-19–21, respectively. Treatment of the iodomethyllactone (+)-16 with LiMe₂Cu or n-Bu₂CuLi furnished the trans-5-alkyl-4-phenyllactones (−)-22 or (+)-23.     

Structural control in palladium(II)-catalyzed enantioselective allylic alkylation by new chiral phosphine-phosphite and pyridine-phosphite ligands

The ligands 6-[(diphenylphosphanyl)methoxy]-4,8-di-tert-butyl-2,10-dimethoxy-5,7-dioxa-6-phosphadibenzo[a,c]cycloheptene, 1, (S)-4-[(diphenylphosphanyl)methoxy]-3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4a′]dinaphthalene, (S)-2, and (S)-4-[(diphenylphosphanyl)methoxy]-2,6-bis-trimethylsilanyl-3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4-a′]dinaphthalene, (S)-3, (S)-2-(3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4-a′]dinaphthalen-4-yloxymethyl)pyridine, (S)-4, and (S)-2-(3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4-a′]dinaphthalen-4-yloxy)pyridine, (S)-5, have been easily prepared.The cationic complexes [Pd(η³-C₃H₅)(L-L′)]CF₃SO₃ (L–L′=1–(S)-5) and [Pd(η³-PhCHCHCHPh)(L–L′)]CF₃SO₃ (L–L′=(S)-2–(S)-4) were synthesized by conventional methods starting from the complexes [Pd(η³-C₃H₅)Cl]₂ and [Pd(η³-PhCHCHCHPh)Cl]₂, respectively. The behavior in solution of all the π-allyl- and π-phenylallyl-(L–L′)palladium derivatives 6–14 was studied by ¹H, ³¹P{¹H}, ¹³C{¹H} NMR and 2D-NOESY spectroscopy. As concerns the ligands (S)-4 and (S)-5, a satisfactory analysis of the structures in solution was possible only for palladium–allyl complexes [Pd(η³-C₃H₅)((S)-4)]CF₃SO₃, 11, and [Pd(η³-C₃H₅)((S)-5)]CF₃SO₃, 12, since the corresponding species [Pd(η³-PhCHCHCHPh)((S)-4)]CF₃SO₃, 13, and [Pd(η³-PhCHCHCHPh)((S)-5)]CF₃SO₃, 14, revealed low stability in solution for a long time. The new ligands (S)-2–(S)-5 were tested in the palladium-catalyzed enantioselective substitution of (1,3-diphenyl-1,2-propenyl)acetate by dimethylmalonate. The precatalyst [Pd(η³-C₃H₅)((S)-2)]CF₃SO₃ afforded the allyl substituted product in good yield (95%) and acceptable enantioselectivities (71% e.e. in the S form). A similar result was achieved with the precatalyst [Pd(η³-C₃H₅)((S)-3)]CF₃SO₃. The nucleophilic attack of the malonate occurred preferentially at allylic carbon far from the binaphthalene moiety, namely trans to the phosphite group. When the complexes containing ligands (S)-4 and (S)-5 were used as precatalysts, the product was obtained as a racemic mixture in high yield. The number of the configurational isomers of the Pd-allyl intermediates present in solution in the allylic alkylation and the relative concentrations are considered a determining factor for the enantioselectivity of the process.     

New succinamic acids, -γ-lactones, and -succinimides from (3-perfluoroalkyl-2-iodoalkyl)succinic acid anhydrides and amines : Highly surface active amphiphiles

The (3-perfluoroalkyl-2-iodoalkyl)succinic anhydrides (4 and 5) react with primary (RNH₂) and secondary amines (RYNH) to yield (3-F-alkyl-2-iodoalkyl)succinamic acids. A second mole of RYNH gives the conjugate bases, 7a and 7b, as two position isomers. Only the C-1 isomer 7a can cyclize to a γ-lactone, while the carboxylate ion intramolecularly displaces iodide ion from CHI as RYNH₂⁺I⁻. Simultaneously, the nucleophilic carboxylate at C-4 in the unreacted isomer 7b attacks the CONHYR group at C-1 to displace the amine and revert to the anhydride 4. Then Step (1) is repeated until all of 7a and 7b are consumed. Though a weak base, COO⁻ is an effective nucleophile in the coiled conformation of 7a or 7b. In the next step, the CH₂(CO)NHR group of the γ-lactone, with an N-attack at the carbonyl rearranges to an N-alkyl (3-F-alkyl-2-hydroxypropyl)succinimide. As above, the lactone opens its ring under stereoelectronic control (with proper alignment of lone pairs on the two O atoms) and forms a new succinimide ring. These reactions occur, successively, in an aprotic, low polarity solvent under mild conditions. Elimination of HI from 4 or 5, or the iodopropylsuccinamic acid, does not occur. Diamines, e.g. (CH₃)₂N(CH₂)₃NH₂ (23) or (CH₃)₂N(CH₂)₃NH(CH₃) (27), reacting with 1 mol of 4 or 5, yield the zwitterionic salt., which inter alia, cyclizes smoothly to the γ-lactone HI salt. The lactone.HI salt from 23, as above, rearranges to the N-(dimethylammonium)propyl (3-F-alkyl-2-hydroxypropyl)succinimide iodide, while the lactone salt 33HI from diamine 27, like that from diethylamine, does not rearrange. Diamine 23, reacting with the t-butyl half ester, R_FCH₂CHICH₂CH(CO₂H)CH₂CO₂C(CH₃)₃, displaces t-butyl alcohol to yield the zwitterionic salt and γ-lactone HI salt, but not the succinimide. Radical addition of R_FI to N-butyl prop-2-enylsuccinimide (100 °C; no solvent) provides the desired adduct in high yield. By contrast, N-(3-dimethylamino)propyl (3-F-alkyl-2-iodopropyl)succinimide (25), loses HI intramolecularly to the basic (CH₃)₂N group; the concentration of 25 is 10 times greater than amines in reactions above. The R_F-surfactants (nonionic, zwitterionic, anionic, and cationic salts) of this work have an oriented F-alkyl segmented tail and a fairly complex polar head; and as a group, they lower the surface tension (γ_a) of water to 15-17 mN m⁻¹ at 1.5-1.7 mM concentration.     

3-Bromo-propenyl acetate in organic synthesis: an expeditious route to 3-alkyl-4-acetoxy-5-iodomethyl isoxazolidines

N-Trimethylsilyloxy-N-benzyl-1-alkyl-2-acetoxy-3-buten-1-amines 13, obtained in good yields and moderate diastereoselectivities by TMSOTf promoted α-acetoxyallylation of nitrones using metallic zinc and 3-bromo-propenyl acetate 11, are exploited in a stereospecific 5-exo-trig iodocyclization reaction to afford 4,5-cis-3-alkyl-4-acetoxy-5-iodomethyl isoxazolidines 14, promising starting materials for the synthesis of pyrrolidine azasugars.     

Synthesis of (+)-1,3,5,7 -tetrakis[2-(1S,3S,5R,6S,8R,10R)-D3-trishomocubanylbuta-1,3-diynyl]adamantane : The first optically active organic molecule with t symmetry and of known absolute configuration

(-)-(1S,3S,5R,6S,8R,10R)-Trishomocubanethanoic acid (5) of known absolute configuration and absolute rotation was converted into (+)-(1S,3S,5S,6S,8R,10R)-2-bromoethynyl-D₃-trishomocubane (27) of C₃ symmetry. 1,3,5,7-Tetraethynyladamantane (22), with Td symmetry, was prepared from 1,3,5,7-tetrakis(hydroxymethyl)adamantane(13). Coupling of the C₃-component 27 with the Td component 22 was successfully accomplished by Chodkiewicz and Cadiot's procedure providing (+)-1,3,5,7-tetrakis[2-(1S,3S,5R,6S,8R,10R)-D₃-trishomocubanylbuta-1,3-diynyl]adamantane(4) whose highest attainable static and time-averaged dynamic symmetry are T and (C₃)⁴ XXX T,respectively.     

Chemo- and diastereoselective control for a flexible approach to (5S,6S)-6-alkyl-5-benzyloxy-2-piperidinones

Chemo- and diastereoselective transformation of the N,O-acetals and their chain tautomers (4/5), readily derived from protected 3-hydroxyglutarimide 1a, was studied. It was uncovered that while the reaction with a combination of boron trifluoride etherate/zinc borohydride led to cyclic products (5S,6S/R)-6-alkyl-5-benzyloxy-2-piperidinones 3/2, and 6 in modest chemo- and diastereoselectivities, the reaction of 4/5 with zinc borohydride led exclusively to the formation of the ring-opening products 6 in excellent anti-diastereoselectivities. On the basis of the latter reaction, a flexible approach to (5S,6S)-6-alkyl-5-benzyloxy-2-piperidinones 3 was disclosed.     

Synthesis,structural characterisation and reactivity of molybdenum half-sandwich complexes containing keto- and amido-phosphines

The keto-functionalised N-pyrrolyl phosphine ligand PPh₂NC₄H₃{C(O)CH₃-2} L¹ reacts with [MoCl(CO)₃(η⁵-C₅R₅)] (R=H, Me) to give [MoCl(CO)₂(L¹-κ¹P)(η⁵-C₅R₅)] (R=H 1a; Me 1b). The phosphine ligands PPh₂CH₂C(O)Ph (L²) and PPh₂CH₂C(O)NPh₂ (L³) react with [MoCl(CO)₃(η⁵-C₅R₅)] in an analogous manner to give the compounds [MoCl(CO)₂(L-κ¹P)(η⁵-C₅R₅)] (L=L², R=H 2a, Me 2b; L=L³, R=H 3a, Me 3b). Compounds 1–3 react with AgBF₄ to give [Mo(CO)₂(L-κ²P,O)(η⁵-C₅R₅)]BF₄ (L=L¹, R=H 4a, Me 4b; L=L², R=H 5a, Me 5b; L=L³, R=H 6a, Me 6b) following displacement of chloride. The X-ray crystal structure of 4a revealed a lengthening of both Mo–P and CO bonds on co-ordination of the keto group. The lability of the co-ordinated keto or amido group has been assessed by addition of a range of phosphines to compounds 4–6. Compound 4a reacts with PMe₃, PMe₂Ph and PMePh₂ to give [Mo(CO)₂(L¹-κ¹P)(L)(η⁵-C₅H₅)]BF₄ (L=PMe₃ 7a; PMe₂Ph 7b; PMePh₂ 7c) but does not react with PPh₃, 5a reacts with PMe₂Ph, PMePh₂ and PPh₃ to give [Mo(CO)₂(L²-κ¹P)(L)(η⁵-C₅H₅)]BF₄ (L=PMe₂Ph 8b; PMePh₂ 8c; PPh₃ 8d), and 6a reacts with PMe₃, PMe₂Ph, PMePh₂ and PPh₃ to give [Mo(CO)₂(L³-κ¹P)(L)(η⁵-C₅H₅)]BF₄ (L=PMe₃ 10a; PMe₂Ph 10b; PMePh₂ 10c; PPh₃ 10d). No reaction was observed for the pentamethylcyclopentadienyl compounds 4b–6b with PMe₃, PMe₂Ph, PMePh₂ or PPh₃. These results are consistent with the displacement of the co-ordinated oxygen atom being influenced by the steric properties of the P,O-ligand, with PPh₃ displacing the keto group from L² but not from the bulkier L¹. In the reaction of [Mo(CO)₂(L²-κ²P,O)(η⁵-C₅H₅)]BF₄ (5a) with PMe₃ the phosphine does not displace the keto group, instead it acts as a base, with the only observed molybdenum-containing product being the enolate compound [Mo(CO)₂{PPh₂CHC(O)Ph-κ²P,O}(η⁵-C₅H₅)] 9. Compound 9 can also be formed from the reaction of 2a with BuLi or NEt₃, and a single crystal X-ray analysis has confirmed the enolate structure.     

Synthesis and reactivity of [(η-[32](1,3)Cyclophane)Mn(CO)3][BF4]

The manganese cyclophane complex, [(η⁶-[3₂](1,3)cyclophane)Mn(CO)₃][BF₄] 2, was prepared by the reaction of [[3₂](1,3)cyclophane] 1 with Mn(CO)₅FBF₃. Reaction of 2 with NaBH₃CN yielded the cyclohexadienyl manganese complex [(η⁵-6H-[3₂](1,3)cyclophane)Mn(CO)₃] 3. Interestingly, treatment of 3 with Mn(CO)₅FBF₃ gave the bis-manganese complex (η⁶,η⁵-6H-[3₂](1,3)cyclophane)[Mn(CO)₃]₂[BF₄] 4. When NaBH₃CN was treated with 4, [(η⁵,η⁵-6H,6^′H-[3₂](1,3)cyclophane)Mn(CO)₃] 5 was isolated as yellow crystals. The structure of compounds 2 and 3 were determined by single-crystal X-ray crystallography.     

Synthesis and characterization of 2-alkyl -5-{4-[(3-nitrophenyl-5-isoxazolyl)methoxy]phenyl}-2H-tetrazoles

Heteroaryl substituted analogs of antirhnoviral (A), was prepared by a convergent approach. 3-Nitrophenyl-5- bromooromethylisoxazoles 5a–b were synthesized by [3+2] cycloaddition of 3-(benzoyloxy)-propyne 2 to in situ generated arylnitrile oxides followed by deprotection of cycloadducts 3a–b and bromination of the resulting alcohols 4a–b. Coupling of 3- nitrophenyl-5-bromooromethylisoxazoles (5a–b) with 4-[5-(2-alkyl-2H-tetrazolyl)]phenols (6a–d) in N-methylpyrrolidinone under mild conditions afforded a new series of 2-alkyl-5-{4-[1-(3-nitrophenyl-5-isoxazolyl)methyloxy]phenylr}-2H-tetrazoles (7a–h) in high yields. The structures of the synthesized compounds were confirmed by their ¹H NMR, Mass spectral, and Elemental Analysis data.     

Bis(diphenylphosphino)methylamine as chelate ligand in pentamethylcyclopentadienylrhodium(III) and iridium(III) complexes.: Crystal structure of [(η5-C5Me5)RhCl{η2-P,P′-(PPh2)2NMe}]BF4

Reactions of the dimers [{(η⁵-C₅Me₅)MCl(μ-Cl)}₂] (M=Rh, Ir) with the ligand NMe(PPh₂)₂ in 1:2 molar ratio afford the mononuclear cationic complexes [(η⁵-C₅Me₅)MCl{η²-P,P′-(Ph₂P)₂NMe}]Cl (M=Rh 1, Ir 2). Similar iodide complexes, [(η⁵-C₅Me₅)MCl{η²-P,P′-(Ph₂P)₂NMe}]I (M=Rh 3, Ir 4), can be prepared by N-functionalization of co-ordinated dppa ligand in complexes [(η⁵-C₅Me₅)MCl{η²-P,P′-(Ph₂P)₂NH}]BF₄. The tetrafluoroborate derivatives, [(η⁵-C₅Me₅)MCl{η²-P,P′-(Ph₂P)₂NMe}]BF₄ (M=Rh 5, Ir 6) are prepared by reaction of complexes 1–4 with AgBF₄ in acetone. All the compounds described are characterised by microanalysis, IR and NMR (¹H, ³¹P{¹H}) spectroscopy. The crystal structure of complex 5 is determined by X-ray diffraction methods. The complex exhibits a pseudo-octahedral molecular structure with a C₅Me₅ group occupying three co-ordination positions and a bidentate chelate P,P′-bonded ligand and a chloride atom completing the co-ordination sphere.     

Synthesis of enantiomerically pure spiro-cyclopropane derivatives containing multichiral centers

A novel chiral source, 5-(R)-[(1R,2S,5R)-(−)-menthyloxy]-3-bromo-2(5H)-furanone (5a), was obtained in 46% yield with d.e.≥98% from the epimeric mixture of 5-(l-menthyloxy)-3-bromo-2(5H)-furanone (5a+5b) obtained via the bromination of an epimeric mixture of 5-(l-menthyloxy)-2(5H)-furanone (3a+3b) followed by the elimination of hydrogen bromide. The asymmetric reaction of 5a with a nucleophilic alcohol afforded enantiomerically pure spiro-cyclopropane derivatives containing four stereogenic centers, 9a–9e, in 50–68% yield with d.e.≥98%. The enantiomerically pure compounds 9a–9e were identified on the basis of their analytical data and spectroscopic data, such as [α]_D²⁰, UV, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The absolute configuration of the chiral spiro-cyclopropane compound 9a was established by X-ray crystallography.     

On the behaviour of the (Z)-phenylhydrazones of some 5-alkyl-3-benzoyl-1,2,4-oxadiazoles in solution and in the gas phase: kinetic and spectrometric evidence in favour of self-assembly

Rate constants, k_A,R, for the rearrangement of the (Z)-phenylhydrazones (1a-e) of a series of 5-alkyl-3-benzoyl-1,2,4-oxadiazoles substituted at C(5) with linear alkyl chains of different length (from C₄ up to C₁₂) into the relevant 4-acylamino-2,5-diphenyl-1,2,3-triazoles (2a-e) have been measured in dioxan/water in the base-catalyzed region (pS⁺ 10.5-12.6). For each substrate log k_A,R are linearly related to pS⁺. The significant decrease of the slopes of these straight lines (from 0.96 down to 0.78) upon increasing the length of the linear alkyl chain at C(5) and that of the reactivity (down to 14-26%) upon increasing the substrate concentration suggest a decrease of the polarity of the ‘actual’ reaction medium and provide indirect evidence of the tendency of the substrates (Z)-1a-e to self-assemble. To confirm the above outcome direct evidence of the formation of self-assemblies in solution were obtained from ¹H NMR and spectrofluorimetry measurements while ESI-MS experiments point out the presence of aggregated substrates also in the gas phase.     

Reactivity and reaction pathways of alkylalkoxybenzene radical cations. Part 3. Effects of 2-alkyl substituents on the relative importance of ring-substitution over deprotonation of 2-alkyl-1,4-dimethoxybenzene radical cations

One-electron oxidation of 2-alkyl-1,4-dimethoxybenzenes 1a-f (2-alkyl=Me, Et, i-Pr, cy-C₃H₅CH₂, PhCH₂ and t-Bu) by 4-nitrobenzoyl peroxide 2 and pentaflurobenzoyl peroxide 3 was proved by the observation of great acceleration of decomposition of the peroxides at room temperature, the detection of the corresponding radical cations 1 ^+? a-f and product analysis. The product studies have disclosed that under the conditions employed (in acetonitrile at 40°C), the reaction pathways of the radical cations are greatly dependent on the nature of 2-alkyl substituents: Ring-4-nitrobenzoloxylation product at C ₅ and C ₆ were obtained exclusively in the reactions of the donors with aliphatic 2-alkyl substituents bearing at least one α-hydrogen atom, such as 1a, 1b, 1c and 1d; whereas in the case of 1e (with 2-benzyl group), both ring-substitution at C ₅ (4e) and C ₆ (5e) and deprotonation/4-nitrobenzoloxylation products 8e were isolated; from the donor without α-hydrogen atom, 1f, de-t-butylation products 12 and t-butyl 4-nitrobenzoate 13 were incorporated with ring-substitution at C ₅ (4f) and C ₆ (5f). Furthermore, the product distribution (4 over 5) is also affected by the bulkiness of 2-alkyl group. For all the electron-transfer reactions, large amounts of the benzoic acid (4-NO₂-C₆H₄COOH or C₆F₅COOH) were generated and trace amounts of de-methylation product (2-alkyl-1,4-benzoqinones 6) were also detected by ¹H NMR.     

Functionalized cyclopalladated compounds with bidentate Group 15 donor atom ligands: the crystal and molecular structures of [{Pd[5-(COH)C6H3C(H)NCy-C2,N](Cl)}2(μ-Ph2PRPPh2)] (R=CH2CH2, Fe(C5H4)2], [Pd{5-(COH)C6H3C(H)NCy-C2,N}(Ph2PCH2PPh2-P,P)][PF6] and [Pd{5-(COH)C6H3C(H)N(Cy)-C2,N}(Ph2PCH2CH2AsPh2-P,As)][PF6]

The chloro-bridged dinuclear compound [{Pd[5-(COH)C₆H₃C(H)N(Cy)-C2,N]}(μ-Cl)]₂ (1), reacts with tertiary diphosphines in 1:1 molar ratio to give [{Pd[5-(COH)C₆H₃C(H)NCy-C2,N](Cl)}₂(μ-Ph₂PRPPh₂)] (R: CH₂, 2; CH₂CH₂, 3; (CH₂)₄, 4; (CH₂)₆, 5; Fe(C₅H₄)₂, 6; trans-CHCH, 7; C≡C, 8). Treatment of 1 with Ph₂PCH₂CH₂AsPh₂ (arphos) gives the dinuclear complex [{Pd[5-(COH)C₆H₃C(H)N(Cy)-C2,N](Cl)}₂(μ-Ph₂PCH₂CH₂AsPh₂)] (9). The reaction of 1 with tertiary diphosphines or arphos in 1:2 molar ratio in the presence of NH₄PF₆ yields the mononuclear compounds [Pd{5-(COH)C₆H₃C(H)NCy-C2,N}(Ph₂PRPPh₂-P,P)][PF₆] (R: (CH₂)₄, 10; (CH₂)₆, 11; Fe(C₅H₄)₂, 12; 1,2-C₆H₄, 13; cis-CHCH, 14; NH, 15) and [Pd{5-(COH)C₆H₃C(H)N(Cy)-C2,N}(Ph₂PCH₂CH₂AsPh₂-P,As)][PF₆] (16). ¹H-, ³¹P-{¹H}- and ¹³C-{¹H}-NMR, IR and mass spectroscopic data are given. The crystal structures of compounds 3, 6, 9 and 16 have been determined by X-ray crystallography.     

Ligand substitution reaction of (μ-H)Os3(CO)10(μ-COMe) with 1,1'-bis(diphenylphosphino) ferrocene

Reaction of (μ-H)Os₃(CO)₁₀(μ-COMe) with 1,1'-bis(diphenylphosphino)-ferrocene (dppf) produces (μ-H)Os₃(CO)₈(μ-COMe){μ-η²-(η⁵-C₅H₄PPh₂)₂Fe} (1) and (μ-H)₂Os₃(CO)₇(μ-COMe){μ-η³-(η⁵-C₅H₃PPh₂)Fe(η⁵-C₅H₄PPh₂)} (2). Thermolysis of 1 leads quantitatively to 2. These compounds have been characterized by ¹H, ³¹P, and ¹³C NMR, IR, and mass spectroscopies. Compound 2 crystallizes in space group P 2₁/c with a = 11.898(2), b = 21.266(3), c = 18.262(3) Å, β = 104.71(1)°, V = 4469(1) ų, Z = 4, and R_F = 0.029.     

Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ-oxaphospholes

The reaction of ethyl propiolate with triphenylphosphine (Ph₃P) in the presence of N-alkylisatins led to ethyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-4-carboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones in good yield. The reaction of dialkyl acetylenedicarboxylates with Ph₃P in the presence of N-alkylisatins led to dialkyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-3,4-dicarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones and alkyl 4-(alkoxy)-5-oxo-2,5-dihydro-3-furancarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones.     

Novel preparation of N′-arylthiocarbamoyl-N,N-dialkylamidines and their synthetic utilities

Treatment of 5-(arylimino)-4-(dialkylamino)-5H-1,2,3-dithiazoles (2) with NaOH in aqueous EtOH at room temperature gave N′-arylthiocarbamoyl-N,N-dialkylamidines (3) in good to excellent yields. The reaction of 3 with sulfur monochloride, thiophosgene, thionyl chloride, sulfuryl chloride, N-phenylimidoyl dichloride, and phthaloyl chloride in CH₂Cl₂ gave 2, 5-(arylimino)-4-(dialkylamino)-Δ³-thiazoline-2-thiones (5), 5-(arylimino)-4-(dialkylamino)-5H-2-oxo-1,2,3-dithiazoles (6), 5-(arylimino)-4-(dialkylamino)-5H-2,2-dioxo-1,2,3-dithiazoles (7), 5-(arylimino)-4-(dialkylamino)-2-(phenylimino)-Δ³-thiazolines (8), and 3-(arylimino)-4-(dialkylamino)-2,5-benzothiazocine-1,6-diones (10) as major products, respectively.     

Diastereoselective intramolecular acyl transfer of 5-(α-methylbenzyl)amino-1,3-dioxan-2-one to 4-hydroxymethyl-2-oxazolidinones

Intramolecular acyl transfer of (R)-5-(α-methylbenzyl)amino-1,3-dioxan-2-one (2) by treatment with DBU in CD₂Cl₂, CDCl₃, C₆D₆, CD₃CN, CD₃NO₂, DMSO-d₆, DMF, THF-d₈, ⁱPrOH, and ^tBuOH at room temperature afforded (4S,αR)-4-hydroxymethyl-3-α-methylbenzyl-2-oxazolidinone [(4S)-3] in moderate to quantitative yields with 58-94% de via an asymmetric desymmetrization process. Treatment of 2 with DBU and Cs₂CO₃ in MeOH and EtOH gave (4S)-3 and (4R)-3 without diastereoselectivities. Acidic treatment of 2 using HCO₂H, AcOH, EtCO₂H, ⁱPrCO₂H, ^tBuCO₂H, and C₆F₅OH in CDCl₃ gave (4S)-3 in moderate diastereoselectivities (26-52% de). First-order kinetics were observed in the reaction of 2 to (4S)-3 with DBU in CDCl₃ and THF-d₈.     

Chiral building-blocks by chemoenzymatic desymmetrization of 2-ethyl-1,3-propanediol for the preparation of biologically active natural products

2-Ethyl-1,3-propanediol 1 and its related di-O-acetate 2 were desymmetrized by partial chemoenzymatic acetylation and deacetylation, by Pseudomonas fluorescens lipase (Amano P.; PFL), to (R)-1-O-acetyl-2-ethyl-1,3-propanediol 3. On treatment of 3 with I₂/Ph₃P/imidazole the related (S)-1-O-acetyl-2-ethyl-3-iodopropanol 4 was obtained and transformed into the corresponding triphenylphosphonium salt 5. Reaction of [(S)-3-acetoxy-2-ethylpropylidene]triphenylphosphorane 6, prepared from 5, with 2,3:4,5-di-O-isopropylidene-β-d-arabino-hexos-2-ulopyranose 7 gave (Z)-3-C-acetoxymethyl-1,2,3,4,5-pentadeoxy-6,7:8,9-di-O-isopropylidene-β-d-manno-dec-4-ene-6-ulo-6,10-pyranose 8 which was hydrogenated to 9 and subsequently deacylated to 10. Treatment of 10 with Me₂CO/H⁺ caused a rearrangement to (3R,4R,5S,6R,9R)-9-ethyl-5-hydroxy-3,4-isopropylidenedioxy-1,7-dioxaspiro[5.5]undecane 11, which closely matched the skeleton of the talaromycins.