Conjugative cycloaddition of N-chlorosulfonyl isocyanate across vinylcyclopropane system. A new pathway towards macro-heterocycles

trans- -Isopropenyl-4-methylene-spiro[2.x]alkanes ($\text{4a}$ and $\text{4b}$) react at 0°C with CSI to give as major products the trans bicyclic cycloazanondienones ($\text{12a}$-$\text{12b}$) and as the minor products bicyclodihydro-azepinones ($\text{11a}$ and $\text{11b}$), and the respective cis isomer of bicyclic cycloazanondienones ($\text{13a}$ and $\text{13b}$).     

Enamine chemistry-XXVI: The [4 + 2] cycloaddition reactions of 3-amino-1-(4-nitrophenyl)-prop-2-ene-1-thione with electrophilic olefins and acetylenes

Enamino-thiones 1 prepared from the corresponding enaminones by thiation with Lawesson's Reagent, were allowed to react with 2-chloroacrylonitrile and dimethyl acetylenedicarboxylate giving dihydro-2$\text{H}$-thiopyrans, 2, and 4$\text{H}$-thipyrans, 3, respectively. The reaction of 1a with ethyl propiolate at room temperature afforded 4$\text{H}$-thipyrans, 4a, which on standing rearranged to 2$\text{H}$-thiopyran, 5a(1, 3 amide shift). The reaction of 1b with ethyl propiolate produced 4b and 5b. Some of the ¹³C NMR data are reported.     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

Photoreactions of 2,3-diazatetracyclo[5.3.1.04,11.06,8]undeca-2,9 dienes ; the retro-1,3-dipolar cycloadditions and the nitrogen extrusion reactions

The photochemical reactions of tetracyclic azo compounds ($\text{1a–b}$) giving $\text{5a–b}$ and $\text{8a–b}$via diazoethane derivatives ($\text{6a–b}$) were investigated in addition to the nitrogen extrusion reactions leading to tetracyclo[4.3.0.0^2,9.05,7nonenes ($\text{4a–b}$).     

Bridgehead nitrogen heterocycles from 2,4,6-triphenyl- pyrylium cation and thiosemicarbazide or thiocarbohydrazide

2,4,6-Triphenylpyrylium with thiosemicarbazide and thiocarbohydrazide, gives 2-pyrazolines $\text{3a}$ and $\text{3b}$ which undergo cyclization yielding pyrazolo(1,5-c]pyrimidine 5 and pyrazolo [2,3-d]-1,2,4-triazepine $\text{7}$ derivatives, respectively. Reaction of $\text{7}$ with phenacyl bromides gave 1,3-thiazolo[3,2-b]pyrazolo [2,3-d]-1,2,4-triazepin-4-iums $\text{10}$. Compound $\text{3a}$ on treatment with phenacyl bromides gave 1-(4'-aryl-thiazol-2'-yl)-2-pyrazoline derivatives $\text{6}$. Compound $\text{3b}$ reacts with acyl chlorides to give pyrazolo[1,5-c]pyrimidine derivatives $\text{14}$, and with aromatic aldehydes giving the 2-(Δ^2'1 pyrazolin-1-yl)-5-aryl-1,3,4-Δ²-thiadiazolines $\text{12}$ which were easily converted to the corresponding 2-(Δ²-pyrazolin-1-yl)-5-aryl-1,3,4-thiadiazoles $\text{13}$.     

2-cyano Δ3 piperidines vi1 : a general method for the stereoselective synthesis of cis and trans 2,6-dialkylpiperidine alkaloids

The cis 2,6-dialkylpiperidine alkaloid (±) dihydro-pinidine $\text{7b}$ and the trans alkaloid (±) solenopsin A $\text{5a}$ were synthesized from a common α-aminonitrile synthon $\text{1}$. The key step in this synthesis was the stereoselective reductive decyanation of the 1-benzyl-2cyano-2′, 6-dialkylpiperidines $\text{3a}$ and $\text{3b}$.     

Formal total synthesis of β-pipitzol

(±)-$\text{O}$-methylperezone ($\text{1b}$) was obtained by selective oxidative demethylation of (±)-leucoperezone trimethyl ether ($\text{4a}$). Compound ($\text{4a}$) was prepared by condensation of 2,3,5-trimethoxytoluene ($\text{5e}$) with 6-methyl-5-hepten-2-one, followed by reductive removal of the tertiary alcohol. The aromatic precursor $\text{5e}$ was prepared in four steps from 2,3-dimethoxytoluene ($\text{5a}$) and, alternatively, in three steps from 5-bromoveratraldehyde ($\text{6a}$). Racemic $\text{1b}$ and $\text{4a}$ were directly compared with the optically active molecules prepared from natural R(-)-perezone ($\text{1a}$).     

Marine natural products: fistularin-1, -2 and -3 from the sponge Aplysina fistularis forma fulva

Three new high molecular weight bromotyrosine-related metabolites, $\text{3a}$, $\text{4a}$ and $\text{5a}$, were isolated from the sponge Aplysina ( Verongia) fistularis forma fulva, and their structures were determined from high resolution ¹H NMR and other spectroscopic data. The new metabolites are formally derived by combination of major segments of two known Aplysina metabolites $\text{1a}$ and $\text{2}$.     

Cobalt metallocycles: XIII. Preparation and x-ray crystallography of cobaltacyclopentadiene and dinuclear cobalt complexes

(η-Cyclopentadienyl)(triphenylphosphine)cobaltacyclopentadienes having an electron withdrawing substituent on the cyclopentadienyl ring, (η-C₅H₄R)(PPh₃)($\text{CoCHCHC}$H) (1b: R = COOMe; 1c: R = COMe), were prepared in reasonable yields by treatment of a solution of (η-C₅H₄R)(PPh₃)₂Co with acetylene. A non-substituted cyclopentadienyl analog (1a: R = H) was also isolated in low yield according to a similar procedure. Novel dinuclear complexes were also formed as by-products and the structure of (η-C₅H₄R)Co(PPh₂$\text{C}{}_6\text{H}{}_4\text{)(μ-C}$Me)Co(η-C₅H₄R) (2b: R = COOMe), having a μ₂,η³-benzyl moiety, was determined by an X-ray crystallographic analysis. The X-ray analyses of 1a and 1b were also carried out. Crystals of 1a are monoclinic, space group Pa, a 8.529(3), b 16.010(6), c 8.028(4) Å, β 100.31(3)°, Z = 2; crystals of 1b are monoclinic, space group P2₁/a, a 8.327(2), b 36.468(7), c 8.021(1) Å, β 98.75(2)°, Z = 4; and crystals of 2b are monoclinic, space group P2₁/c, a 10.681(2), b 30.722(7), c 8.912(1) Å, β 93.55(1)°, Z = 4. They have been refined to R = 0.034, 0.047 and 0.050, respectively.     

Formation of an iridium σ-cyclopropane complex by the intramolecular activation of a cyclopropylphosphine: Rearrangement to a chelating σ-vinyl complex

When (t-Bu)₂PCH₂CHCH₂CH₂ is combined with [IrCl(C₈H₁₄)₂]₂ in toluene, the σ-bound cyclopropane complexes

(P(t-Bu)₂CH₂$\text{CHCH}{}_2\text{C}$H₂) (1a, 1b) are formed. Complexes 1a,1b react readily with H₂ to form IrClH₂P(t-Bu)₂CH₂$\text{CHCH}{}_2\text{C}$H₂)₂ (2). In polar solvents 1a,1b isomerize to the σ-vinyl chelated complex $\text{IrClH(P(t-Bu)}{}_2\text{CH}{}_2\text{C(CH}{}_3\text{)C}$H)(P(t-Bu)₂CH₂$\text{CHCH}{}_2\text{C}$H₂) (3). The structure of this 5-coordinate, 16-electron Ir^III complex was deduced from spectroscopic data, reaction chemistry, and from the crystal structure of its CO adduct (4). Compound 4 crystallizes in the monoclinic space group C_2h⁵-P2₁/n (a 15.610(14), b 15.763(16), c 11.973(13) Å, and β 104.74(5)°) with 4 molecules per unit cell. The final agreement indices for 2326 reflections having F_o² > 3σ(F_o²) are R(F) = 0.089 and R_w(F) = 0.095 (271 variables) while R(F²) is 0.148 for the 3423 unique data. Bond lengths in the 5-atom chelate ring $\text{IrPCCC}$ are IrP 2.341(4), PC 1.857(26), CC 1.520(30), CC 1.341(25), and CIr 1.994(21) Å. The IrCl distance is 2.479(5) Å.     

Synthesis of oxazolidin-2-ones using carbonate ion on a polymeric support

Through the insertion of a carbon dioxide molecule, the oxazolidin-2-ones ($\text{5a}$) and ($\text{5b}$) were prepared by treataent of the salts ($\text{4a}$) and ($\text{4b}$) with carbonate anion on polymeric support. The hydrolysis under basic conditions of ($\text{5a}$) and ($\text{5b}$) afforded the erythro-3-amino-1,2-diols ($\text{6a}$) and ($\text{6b}$) which were fully acetylated: the 2-amino-2-deoxyerythritol derivative ($\text{7b}$) was obtained in 91% yield.     

Studies on amino acids and peptides VIII : Synthesis and crystal structure of two monothiated analogues of Boc-Gly-S-Ala-Aib-OMe

The model tripeptide Boc-Gly-S-Ala-Aib-OMe ($\text{2b}$) and the two monothiated analogues Boc-Gly(¹ψ²CSNH)-S-Ala-Aib-OMe ($\text{2c}$) and Boc-Gly-S-Ala(²ψ³ CSNH)-Aib-OMe ($\text{2a}$) were synthesized. Peptide $\text{2a}$ was obtained by thiation of $\text{1a}$ using 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, Lawesson's Reagent (LR), followed by deprotection of the Boc group and coupling with Boc-Gly-OH. Thiation of $\text{2b}$ with LR regiospecifically transformed the protected tripeptide to the monothiated analogue $\text{2c}$. X-Ray diffraction analysis showed that the type-III β-turn formed by the reference peptide $\text{2b}$ is preserved in the monothiated analogue $\text{2a}$; conversely,the structure of the isomeric tripeptide $\text{2c}$ is partially extended.     

Reaction between nucleoside base residues and the phosphorylating agent derived from 1-hydroxybenzotriazole and 2-chloroprenyl phosphorodichloridate

In the presence of 1-methylimidazole, 2-$\text{N}$-acyl guanine (as in $\text{4a}$), thymine (as in $\text{5a}$) and uracil (as in $\text{5b}$) residues react readily with the phosphorylating agent derived from 2-chlorophenyl phosphorodichloridate ($\text{1a}$) and 1-hydroxybenzotriazole.     

Chemistry of 4-membered cyclic nitrones (2, 3-dihydroazete 1-oxides); a novel one-step synthesis of N-acetoxy β-latams

2,3-dihydroazete 1-oxide $\text{1}$ reacts at room temperature with base, acid and lead tetraacetate to give the 5-hydroxyisoxazolidines $\text{4a}$ and $\text{4b}$, the 6H-1,2-oxazin-6-one $\text{7}$ and the N-acetoxy β-lactam $\text{8}$, respectively; the reaction with lead tetraacetate represents a simple one-step conversion of a 4-membered cyclic nitrone into a β-lactam.     

High diastereoselection in the claisen rearrangement of enantiomerically pure butyrolactones

The Claisen rearrangement permits the stereoselective formation of butyrolactone $\text{5b,c}$ or $\text{13b,c}$ through the utilization of enantiomeric lactone $\text{1a}$ and enantiomeric alcohols $\text{2b}$, ent-$\text{2b}$, $\text{2c}$, and ent-$\text{2c}$.     

Synthesis of enantiomerically enriched atrolactic acid and other α-hydroxy acids

The α-anions of 2-substituted 1,3-dioxolan-4-ones derived from chiral mandelic and lactic acid ($\text{2a}$, $\text{2b}$; $\text{3a}$; $\text{10a}$, $\text{10b}$) were alkylated with high stereoselectivity. The products formed were hydrolysed to α-hydroxy acids with 65–85% e.e. ((S)(+)-$\text{5}$,$\text{7}$,$\text{9}$, (R)(–)-$\text{13}$).     

On the mode of incorporation of leucine samples labelled at positions 5 and 2 with 3H and 14C into the isoprenylated tryptophan derivative echinuline from aspergillusamstelodami

Feeding experiments with (4$\text{S}$) [5-³H;5-¹⁴C]$\text{L}$-leucine ($\text{1a}$) and with the (4$\text{S}$) [5-³H;2-¹⁴C]-isomer ($\text{1b}$) show that incorporation into the isoprenylated tryptophan derivative echinuline ($\text{3}$), produced by $\text{Aspergillus}$$\text{amstelodami}$, involves, to a large extent, loss of the fragment enbodying the carbon atom at position 2 of the fed amino acid.     

Zur konformation und intramolekularen beweglichkeit von [6]paracyclophan-8,9-dicarbonsäurediethylester)

The title compound 1 prepers the conformations $\text{1a}$/$\text{1b}$ predicted for [6]paracyclophane; the barrier for the intramolecular process $\text{la}$ ? $\text{1b}$ was found to be Δ G⁺ = 13.9 kcal/mol at +4°C.