The synthesis of γ-fluoroisoleucine

Condensation of 3-fluoro-2-butanone ($\text{2}$) with alkyl diethylphosphonoacetates ($\text{4a–d}$) gave alkyl 4-fluoro-3-methyl-2-pentenoates ($\text{5a–d}$). Addition of bromine yielded alkyl-2,3-dibromo-4-fluoro-3-methylpentanoates ($\text{6a,b}$) which were dehydrobrominated to alkyl 2-bromo-4-fluoro-3-methyl-2- pentenoates ($\text{7a,b}$). Since these compounds could not be hydrogenated to the desired alkyl 2-bromo-4-fluoro-3-methylpentanoates ($\text{8a,b}$), another route was taken. The esters $\text{5a–d}$ were hydrogenated to alkyl 4-fluoro-3- methylpentanoates ($\text{11a–c}$) which were converted to their carbanions. Treatment with bromine gave esters $\text{8a–c}$, and iodine gave alkyl 4-fluoro-2-iodo- 3-methylpentanoates ($\text{12a,b}$). Esters $\text{8a–c}$ and $\text{12a,b}$ were converted to alkyl 2-azido-4-fluoro-3-methylpentanoates ($\text{13a–c}$) whose hydrogenation gave alkyl 2-amino-4-fluoro-3-methylpentanoates ($\text{14a–c}$). Hydrolysis afforded γ-fluoroisoleucine ($\text{1}$).     

Stereoselective syntheses of substituted methyl (Z,E,E)-deca-2,7.9-trienoates and substituted methyl (Z,E,E)-undeca-2,8,10-trienoates

Lindlar hydrogenation of substituted methyl ($\text{E}$,$\text{E}$)-deca-7,9-dien-2-ynoates and substituted methyl ($\text{E}$,$\text{E}$)-undeca-8,10-dien-2-ynoates affords selectively the corresponding ($\text{Z}$,$\text{E}$,$\text{E}$)-trienes.     

Synthesis and intramolecular cyclisation of ortho-hydroxy-2,3,3,3-tetrafluoropropiophenone. Formation of 3-fluoro-4-hydroxycoumarin

Acidic hydrolysis of 1-(o-methoxyphenyl)pentafluoropropene $\text{1}$ gave o-hydroxy-2,3,3,3-tetrafluoropropiophenone $\text{2}$ and o-methoxy-2,3,3,3-tetrafluoropropiophenone $\text{3}$. Compound $\text{2}$ when treated with aqueous potassium hydroxide or methanolic sodium methoxide gave 3-fluoro-4-hydroxycoumarin $\text{4}$. Structure of $\text{4}$ has been established by spectral means and some chemical reactions. The cyclisation mechanism of $\text{2}$ is discussed.     

Palladium-catalyzed asymmetric cyclization of methyl (E)-oxo-9-phenoxy-7-nonenoate and its analogs

Asymmetric cyclizations of methyl (E)-3-oxo-9-phenoxy-7-nonenoate ($\text{1}$) or methyl (E)-3-oxo-9-(methoxycarbonyl)oxy-7-nonenoate ($\text{4}$) without added base were carried out in the presence of a catalytic amount of palladium(II) acetate and chiral diphosphine as ligands. Allylic carbonate $\text{4}$ reacted by use of Pd(OAC)₂-(S)-(R)-BPPFA at room temperature to give (R)-3-vinylcyclohexanone ($\text{3}$), after decarboxylation, in up to 48% e. e.     

Halogen cleavage reactions of cis-(threo-PhCHDCHD)Mn(CO)4PEt3

Halogen cleavage reactions of $\text{cis}$-($\text{threo}$-PhCHDCHD)Mn(CO)₄, PEt₃ ($\text{3}$) are studied in detail and are found to proceed either predominantly with retention or inversion, or non-stereospecifically, depending on reaction conditions. Reaction mechanisms involving S_E2 (inversion), S_E2 (retention) and S_E (oxidative) processes are proposed, demonstrating that halogen cleavage reactions of $\text{3}$ straddle the mechanistic borderline between electrophilic substitution and oxidation processes of transition metal alkyl compounds.     

Addition dipolaire-1,3 aux olefines portant une substitution captodative: reactivite comparee des α et des β amino acrylnitriles vis a vis des arylazides.

Arylazides reacted with α amino-acrylonitriles $\text{1}$ to produce 1-aryl-5-amino-triazoles, and with β amino-acrylonitriles $\text{2}$ to give 1-aryl-4-cyanotriazoles. Kinetics showed the Hammett ρ to be > o and therefore, these reactions are controlled by LUMOazide-HOMOolefin interaction. Despite the captodative substitution in $\text{1}$ and $\text{2}$ (ΔΔ E^≠～ 500 cal.M^?1) does'nt agree with a diradical intermediate.     

Reaction of benzothiazoline with benzyne - generation of novel heterocyclic sulfur ylide,benzothiazolinium s-ylide

A novel heterocyclic sulfur ylide, 2-t-butyl-3-methyl-1-phenylbenzothiazolinium ylide ($\text{13}$) was generated as an intermediate in the reaction of 2-t-butyl-3-(nethy1benzothiazoline ($\text{2}$) with benzyne. The S-ylide $\text{13}$ underwent a novel intermolecular [1,2] shift to give 2-t-butyl-3-methyl-2-phenylbenzothiazoline ($\text{4}$).     

4,6-Thioanhydro-hexopyranosides,synthesis and chemical behaviour of methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-d-gulopyranoside

Methyl 4-0-benzoyl-6-bromo-6-deoxy-α-D-glucopyranoside ($\text{1}$, Figure 1) was converted, via the corresponding ditosylate $\text{2}$, into methyl 2,3-di-0-p-toluenesulfonyl-4-0-benzoyl-6-S-acetyl-6-thio-α-D-glucopyranoside ($\text{3}$) by a selective nucleophilic displacement of 6-bromo-group with thioacetate. Unexpectedly, on treating the compound $\text{3}$ with an excess of sodium methoxide in benzene-methanol (1:1) at room temperature, methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyranoside ($\text{4}$) was obtained in a yield of 84%. In order to determine the structure of the relatively unstable oily product $\text{4}$, some stable crystalline derivatives ($\text{5}$, $\text{6}$ and $\text{7}$) were prepared. Detailed analysis of the ¹H-NMR-spectra (200 MHz) of $\text{6}$ and $\text{7}$ gave the conclusive evidence for the structure of $\text{4}$ A self-imposing mechanism of the clean and smooth transformation of $\text{3}$ to $\text{4}$ is proposed, involving: a) formation of $\text{9}$ (Figure 2) as a crucial intermediate and b) a highly regioselective epoxide opening in $\text{9}$ (at C-4) by an intramolecular nucleophilic attack of the mercaptide anion from C-6.     

Stereospecific synthesis of (5E)-PGE2 by palladium-catalyzed decarboxylative 2-alkenylation of 2-alkenyloxycarbonylated cyclopentanone derivative

(5$\text{E}$)-Prostaglandin E₂ methyl ester was synthesized from ($\text{R}$)-4-$\text{t}$-butyldimethylsiloxy-2-cyclopentenone by $\text{in}$$\text{situ}$ 2-alkenyloxycarbonylation of the organocopper conjugate-addition adduct followed by intramolecular palladium-catalyzed decarboxylative 2-alkenylation. A ($\text{E}$)-2-butenylated cyclopentanone derivative was obtained from either 2-[($\text{E}$)- or ($\text{Z}$)-2-butenyloxy-carbonyl]cyclopentanone derivative under the similar reaction condition.     

Vicinal diester dianions. Annelation with ω-bromoesters. A simple preparation of bicyclo[4.4.0] decan-2-one derivatives valuable in sesquiterpene synthesis.

The dianion of dimethyl, cyclohex-4-ene-1,2-dicarboxylate ($\text{1}$) can be annelated with ethyl 4-bromobutyrate ($\text{2}$) to give cis-dimethyl 1,2,3,5-tetrahydro-1-oxo-4a(4H), 8a (8H)-naphthalenedicarboxylate ($\text{5}$), which is readily transformed into $\text{8a}$, a synthetic intermediate for a number of sesquiterpene syntheses.     

The synthesis of the potent anti-herpes virus agent, E-5(2-bromovinyl)-2′-deoxyuridine and related compounds

The synthesis of $\text{E}$-5(2-bromovinyl)-2′-deoxyuridine in good yield from deoxyuridine $\text{via}$ an intermediate organopalladium derivative is described. The corresponding chloro and iodo compounds have also been made as have the corresponding bromo and iodo 2′-deoxycytidines.     

Synthesis of carboxylic esters using formaldehyde dimethyl dithioacetal S,S-dioxide

Formaldehyde dimethyl dithioaoetal S,S-dioxide ($\text{1}$) reacted uith an alkyl bromide or a 2-alkenyl bromide ($\text{8}$) under phase-transfer sonditions using 50% aq. NaOH to give an alkyl or 2-alkenyl derivative of $\text{1}$, whereas, in the reaction with $\text{8}$ in the presence of Kg₂CO₃KI in HMPA, $\text{1}$ formed a 1-alken-3-yl derivative. Transformation of these products into the corresponding carboxylio esters uae also described.     

Photoisomerization of benzylidenephosphine containing phosphorus in low coordination state

$\text{E}$-Benzylidene-$\text{P}$-2,4,6-tri-$\text{t}$-butylphenylphosphine containing phosphorus in low coordination state was irradiated to give the corresponding $\text{Z}$-isomer: both isomers were isolated and characterized and the reactions with chromium(O) carbonyls were described.     

Short synthesis of 6-oxoprostaglandin E1 and 6-oxoprostaglandin F1α

6-Oxoprostaglandin E₁ methyl ester was synthesized in a single pot from ($\text{R}$)-4-$\text{t}$-butyldimethylsiloxy-2-cyclopentenone by organocopper conjugate addition with an ω side-chain unit, trapping of the resulting enolate with 6-methoxycarbonyl-2-nitrohex-1-ene, and treatment with aqueous titanium(III) trichloride. Hydrolysis of the methyl ester was accomplished by porcine liver esterase. 6-Oxoprostaglandin F_1α, was obtained from 6-nitroprostaglandin E₁ methyl ester in four steps.     

Discrete introduction of the electrophile and nucleophile in AdE -reactions of dicobalt hexacarbonyl complexes of conjugated enynes.

The dicobalt hexacarbonyl complex of the enyne isopropenylacetylene ($\text{1}$) is effective in permitting stepwise Ad_E reactions to the double bond of $\text{1}$ via stabilization of the intermediate carbenium ion.     

Completely stereoselective synthesis of all four stereoisomeric 1-carbamoyloxy-1,3-alkadienes via anti-diastereoselective homoaldol reaction from aldehydes and a single carbon-three-unit

Lithiation of both ($\text{Z}$)- and ($\text{E}$)-3-trimethylsilyl-2-propenyl $\text{N}$,$\text{N}$-diisopropyl carbamate 2 affords the (2$\text{E}$) -lithium compound 3. Aluminium- or titanium-mediated addition to aldehydes, 4 gives (1$\text{E}$)-(3$\text{R}$*4$\text{S}$*)-enol carbamates 7. A stereospecific Peterson elimination (borontriflouride- or base-mediated) introduces the second double bond either with (3$\text{E}$)- or with (3$\text{Z}$)-configuration. So just by reagent selection for each of the two steps, (1$\text{E}$,3$\text{E}$)-, (1$\text{E}$,3$\text{Z}$)-, (1$\text{Z}$,3$\text{E}$)-, or (1$\text{Z}$,3$\text{Z}$)- dienes 8 - 11, respectively, are prepared with stereoselectivities up to > 99.7%     

Aldol diastereoselection via zirconium enolates. Product-selective,enolate structure independent condensations.

Both($\text{E}$)- and ($\text{Z}$)-zirconium enolates have been shown to undergo selective kinetic aldol condensation to give mainly $\text{erythro}$-β-hydroxy ketones, esters and amides.     

Models of folate coenzymes 14: An alternate approach to the yohimbane skeleton

The anion of dimethyl homophthalate adds to imidazolinium and tetrahydropyrimidinium salts ($\text{2a,b}$) to yield imidazolidine and tetrahydropyrimidine adducts corresponding to methylenetetra-hydrofolate models ($\text{3a,b}$). These models transfer the carbon fragment 2-(MeOOC)C₆H₄CH(COOMe)CHXXX to tryptamine to give an enamino ester intermediate which is cyclized, in two steps to the yohimboid skeleton.     

Interactions of singlet oxygen with 2,5-dimethyl-2,4-hexadiene in polar ano non-polar solvents evidence for a vinylog ene-reaction

2,5-Dimethyl-2,4-hexadiene ($\text{1}$)was studied as a singlet oxygen acceptor in various solvents. $\text{1}$undergoes concomitantly the three well-known modes of singlet oxygen reactions: (1) the ene-reaction to give the allylic hydroperoxide $\text{3}$, (2) the (4+2)-cycloaddition to give the endoperoxide $\text{4}$, and (3) the (2+2)-cycloaddition to give the dioxetane $\text{2}$. Beyond that (and in contrast to simple olefins), there are (4) “physical” quenching and (5) a “vinylog ene-reaction” to give the twofold-unsaturated hydroperoxide $\text{5}$. The latter reaction represents a novel mode of singlet oxygen interaction with a substituted 1,3-diene. - Kinetic analysis shows that “physical” quenching, endoperoxide and vinylog ene-product formations proceed with solvent-inde pendent rates; the rates of dioxetane and ene-product formations, however, are solvent-dependent. - A mechanism (Scheme 3) is proposed, according to which endoperoxide formation is due to a concerted singlet oxygen reaction with the s-cis-conformational isomer $\text{1b}$; with the s-trans-isomer $\text{1a}$, “physical” quenching and the vinylog ene-reaction proceed via a non-polar singlet diradical intermediate, whereas the ene-product formation occurs via a per epoxide-like transition state. In aprotic solvents, the dioxetane is mainly formed via a “tight-geometry intermediate”, in methanolic solution via a solvent-stabilized zwitterion; the latter is also responsible for the formation of the methanol-addition product $\text{6}$.