3-Bromo-2-(tert-butylsulfonyl)-1-propene. A multi-coupling reagent Part 1.

3-Bromo-2-(tert-butylsulfonyl)-1-propene $\text{4}$ is easily available in two steps from allyl-tert-butylthioether $\text{5}$ (70% overall yield). It reacts with a great variety of carbanions to give functionnalized α, β-unsaturated sulfones of type $\text{7}$ in high yields. A second nucleophile (lithium cuprates) can then be added to compounds $\text{7}$ to furnish functionnalized sulfones of type $\text{3}$ (Y=SO₂-tert-butyl).     

A novel synthesis of linear polyenes via conjugate addition of cuprates to α,β-γ,δ-diunsaturated sulfones followed by SO2 extrusion

The two 1,3-butadienyl 2-propenyl sulfones $\text{5}$ and $\text{6}$, 1,3,5-heptatriene synthons, have been transformed into the tri- and tetraenes $\text{1}$ - $\text{4}$ by alkylcuprate addition and Ramberg-Bäcklund SO₂ extrusion. The reaction stereochemistry is discussed.     

1,3-Dipolar cycloaddition reactions of pyrazolidinium ylides with vinyl sulfones. A regioselective synthesis of bicyclic pyrazolidinone antibacterial agents

The 1, 3-dipolar cycloaddition reaction of pyrazolidinium ylide $\text{1}$ with substituted vinyl sulfones $\text{5}$ was studied. Elimination of benzenesulfinic acid from the resulting cycloadducts gave rise to bicyclic pyrazolidinones $\text{3}$. The (E)-olefin isomers were found to undergo cycloaddition in a highly regioselective fashion. These pyrazolidinones $\text{3}$ represent the nuclei of an exciting new class of potent antibacterial agents that mimic β-lactams.     

1-Benzenesulfonyl-2-trimethylsilylethane and 1-benzenesulfonyl-1-chloro-2-trimethylsilylethane; efficient reagents for sulfonyl-α-vinylation

1-Benzenesulfonyl-2-trimethylsilylethane and 1-benzenesulfonyl-1-chloro-2-trimethylsilylethane are convertable to 1-benzenesulfonyl-1-chloro-1-substituted-2-trimethylsilylethanes which undergo elimination by fluoride ion to give phenyl $\text{α}$-substituted-vinyl sulfones.     

A highly efficient radical clock as a probe of the mechanism of sulfone halogenation by perhaloalkanes

Halogenation of (endo)-5-(2-i-propylsulfonyl)-2-norbornene 5, a new highly efficient radical probe, shows that if an SET mechanism was occurring in the -α-halogenation of sulfones by perhaloalkanes, it would have to involve a reaction step in which a C-centered radical reacts with CX₄^$\text{.}$ at a rate greater than 10¹⁰ s^?1.     

3-Bromo-2-(tert-butylsulfonyl)-1-propene. A multi-coupling reagent. Part 2. <1

3-bromo-2-(tert-butylsulfonyl)-1-propene 1 reacts in good yields with various electrophiles (aldehydes, ketones, nitriles and alkynes) in the presence of zinc metal to give unsaturated sulfones of type 4. These compounds can further react with soft or hard nucleophiles (alkyl-, vinyl-, aryllithium compounds, a nitroparaffin or dimethylmalonate) to yield highly functionnalized sulfones of type 5 which can be readily transformed into enones or into a dienone. Thus sulfone 1 is a versatile multi-coupling reagent which is synthetically equivalent to the $\text{a}{}^2\text{a}{}^{\mathrm{2\prime }}$ synthon 8 and to the $\text{d}{}^2\text{d}{}^{\mathrm{2\prime }}$ synthons 9 and 10.     

Cycloaddition reactions of 2,3-didehydrothiophene generated by flow vacuum thermolysis of thiophene-2,3-dicarboxylic anhydride

Flow vacuum thermolysis (FVT) of thiophene-2,3-dicarboxylic anhydride ($\text{2}$) in the presence of 2,3-dimethylbutadiene ($\text{6}$) gives, in addition to 5,6-dimethylthianaphthene ($\text{9}$). small quantities of a dihydrodimethylthianaphthene ($\text{12}$) and another dimethylthianaphthene ($\text{13}$) which is probably also formed by dehydrogenation of $\text{12}$ with chloranil. The partial structures of these minor products are consistent with their being formed by a [2+2]-cycloaddition between $\text{6}$ and an intermediate aryne, 2,3-didehydrothiophene ($\text{1}$), followed by a rearrangement of the resulting adduct $\text{11}$ and dehydrogenation. FVT of $\text{2}$ in the presence of 2,5- ($\text{17b}$) or 3,4-dimethylthiophene ($\text{17c}$) also gave a mixture of the dimethylthianaphthenes ($\text{18}$$\text{22}$, $\text{23}$) which can be rationalized as arising by a [4+2]- and two [2+2]-cycloadditions of the aryne $\text{1}$ to the thiophenes $\text{17}$ with subsequent desulfurization. The lack of equilibration of the products $\text{18}$, $\text{22}$ and $\text{23}$, was demonstrated and their origin as a function of the structure and reactivity of the aryne $\text{1}$ discussed.     

Facile syntheses of 2,4,6-cycloheptatrienyl ketones

The synthesis of the 2,4,6-cycloheptatrienyl ketones $\text{1a}$–$\text{1e}$ by two alternative routes is reported: Route 1): The adducts $\text{3a–c}$ from the phenyl(trimethylsiloxy)-acetonitriles $\text{2a–c}$, known as “umpolung” reagents, and tropylium tetrafluoroborate are cleaved by triethylammonium fluoride to form the aromatic cycloheptatrienyl ketones $\text{1a}$–$\text{1c}$. Route 2): the phenyl, methyl, and cyclopropyl ketone ($\text{1a}$, $\text{1d}$, $\text{1e}$) are prepared by treatment of the acid chloride $\text{7}$ with the corresponding organomanganese iodides RMnI ($\text{8a}$, $\text{8d}$, $\text{8e}$). The Fe-catalyzed coupling reaction of the acid chloride $\text{7}$ with a Grignard reagent was also used for the preparation of ketone $\text{1b}$.     

Photooxygenation of bicyclopropylidene

Upon photooxidation bicyclopropylidene ($\text{1}$) yields spiro[2.3]hexan-4-one ($\text{4}$) and 7-oxatrispiro[2.0.2.1]heptane ($\text{6}$). The formation of these is rationalized. Authentic $\text{6}$ was prepared by epoxidation of $\text{1}$, and $\text{4}$ by isomerization of $\text{6}$.     

Synthesis of binzindene prostaglandins: a novel potent class of stable prostacyclin analogs

The phenols $\text{13}$, $\text{16}$, and $\text{21}$, produced with remarkable regioselectivity by the cyclization of compounds $\text{10}$ and $\text{12}$, have been converted to the benzindene prostaglandin analogs $\text{25}$, $\text{20}$, and $\text{24}$, respectively. Compounds $\text{24}$ and $\text{25}$ are potent prostacyclin mimics.     

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 ($\text{1a}$).     

Synthesis of 3,3,3-trifluoropropionic and 4,4,4-trifluoro-2-ketobutyric acids

Trifluoroethyl cyclohexyl ketone ($\text{4}$) is prepared by acylation of difluoroethylene ($\text{2}$) with cyclohexanecarboxylic acid chloride ($\text{1}$), followed by Cl→F exchange with potassium fluoride in the presence of triethylbenzyl- ammonium chloride. Bayer-Villiger oxidation of ketone ($\text{4}$) with trifluoroperacetic acid gives cyclohexyl trifluoropropionate ($\text{5}$). 3,3,3-trifluoropropionic acid ($\text{6}$) is obtained by treatment of ($\text{5}$) with trimethylsilyl iodide. Condensation of 2,2,2-trifluorodiazoethane ($\text{7}$) with ethyl glyoxylate ($\text{8}$) gives mainly ethyl 4,4,4-trifluoro-2-ketobutyric acid ester ($\text{9}$) which leads after hydrolysis to the corresponding acid ($\text{12}$).     

Pyridazines XXIV: Application of radicalic ethoxycarbonylation to the synthesis of pyridazine mono- and polycarboxylic acid esters

Reactivity of pyridazines $\text{1}$, $\text{2}$, $\text{3}$, $\text{16}$ towards ethoxycarbonylradical (generated by redox decomposition of oxyhydroperoxide of ethylpyruvate) was studied. Application of this type of homolytic substitution for synthesis of hitherto not accessible pyridazine carboxylic acid esters $\text{6}$, $\text{8}$, $\text{9}$, $\text{12}$, $\text{13}$, $\text{14}$, $\text{15}$, $\text{17}$ is demonstrated. In addition improved synthesis of diethyl 4,5-pyridazinedicarboxylate ($\text{5}$) is proposed.     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.     

Preparation of perfluoroalkylthiohydroximates from perfluoroalkyl nitriles

S-Methyl($\text{Z}$)-2,2,2-trifluorothioacetohydroximate ($\text{1}$), S-methyl($\text{Z}$)-2,2,3,3,3-pentafluorothiopropiohydroximate ($\text{2}$), and S-methyl($\text{Z}$)-2,2,3,3,4,4,4-heptafluorothiobutyrohydroximate ($\text{3}$) were prepared by reaction of the corresponding perfluoroalkyl nitriles $\text{4}$, $\text{5}$, and $\text{6}$ with methanethiol and hydroxylamine hydrochloride.     

Cycloaddition reactions of 1,3-benzothiazines - 6. Reactions of 1,3-benzothiazine derivatives with substituted acetyl chlorides

6, 7-Dimethoxy-2$\text{H}$-l,3-benzothiazine derivatives ($\text{1}$, $\text{8}$) react with substituted acetyl chlorides to give angularly condensed β -lactams ($\text{3a}$-$\text{d}$, $\text{10}$, $\text{11}$). The $\text{cis}$ compound $\text{11}$ was epimerised to the $\text{trans}$ derivative $\text{12}$. From the interaction of 2-phenyl-6,7-dimethoxy-4$\text{H}$-1,3-benzothiazine ($\text{7}$) and α -chloro-phenylacetyl chloride two stereoisomeric β -lactam derivatives ($\text{9a}$, $\text{b}$) were isolated, whereas in the other cases studied the reactions leading to β -lactams proved to be stereospecific. Analogous reactions of $\text{4}$-methyl-6,7-dimethoxy-2$\text{H}$-l,3-benzothiazine ($\text{5}$) furnished the enamides $\text{6a}$,$\text{c}$, $\text{d}$. Structures of the new compounds and configurations of the diastereomers were elucidated by IR and NMR spectroscopy.