Synthesis of 4′-amino-4′-deoxy analog of pantothenic acid

The synthesis of $\text{D}$- and $\text{L}$-N-(4-amino-3, 3-dimethyl-2-hydroxybutyryl)- β-alanine ($\text{7}$) is described. Compound $\text{7}$ is an analog of pantothenic acid in which the 4′-hyroxy group is replaced by amino group. The synthetic sequence leading to $\text{7}$ involved the synthesis $\text{D}$L-4-amino-3,3-dimethyl-2-hydroxybutyric acid and its resolution. Coupling of N-benzyloxycarbonyl N-hydroxysuccinimide ester ($\text{5}$) with β-alanine and followed by removal of the protecting group gave $\text{7}$.     

Chiral synthesis of statine

Statine ($\text{8a}$) has been obtained in high enantiomeric purity as its N-Boc-ethyl ester ($\text{8b}$) in a chiral synthesis. The sequence involves the enantio- and erythro-selective aldol condensation of N-Boc-L-leucinal ($\text{5}$) with (S)-4-(1-methylethyl)-3-[(methylthio)acetyl]-2-oxazolidinone ($\text{1}$) via the boron enolate, followed by desulfurization and saponification in ethanol, according to the methodology of Evans.     

(-)-β-Pinene as chiral promoter. Stereospecific access to (-)-γ-amino-β(r)-hydroxybutyric acid (gabob) and (r)-carnitine.2

The stereochemical correlation between the ene adducts 2 and 4a and their products of alkaline hydrolysis is reported. Starting from 2, by using a degradative sequence, a stereocontrolled approach to γ-amino-β($\text{R}$)-hydroxybutyric acid (GABOB) 8f and ($\text{R}$)-carnitine hydrochloride 8g is described.     

Methylated multibridged [2n]cyclophanes. All alternate synthesis of [26](1,2,3,4,5,6) cyclophane (superphane)

A sequence of formylation followed by a carbene insertion reaction has led to the stepwise introduction of additional ethano bridges into 4,5,7,8- tetramethyl [2₂](1,4)cyclophane ($\text{1}$), providing syntheses of 5,7,8-trimethyl- [2₃](l,2,4)cyclophane ($\text{6}$), a mixture of 5,8-dimethyl[2₄(1,2,4,5)cyclophane ($\text{10}$) and 5,7-dimethyl[2₄(1,2,3,5)cyclophane ($\text{11}$, and-4-methyl[2₅](1,2,3,4,5)-cyclophane ($\text{14}$). This route to $\text{14}$ completes a formal eight-step synthesis of [2₆](1,2,3,4,5,6)cyclophane ($\text{15}$, superphane) with an overall yield of 17%. A Birch reduction of $\text{6}$ readily gave 12,15-dihydro-5,7,8-trimethyl[2₃](1,2,4)-cyclophane ($\text{7}$) in 85% yield.     

Furannulation via radical cyclisation

A three step 4-methyl furan annulation sequence is described $\text{via}$ the radical cyclisation of bromoacetal $\text{3}$to 2-alkoxy-4-methylene tetrahydrofuran $\text{4}$     

Intramolecular diels-alder reaction with furan-diene: Total synthesis of (±)-11-ketotestosterone and (±)-adrenosterone

A novel D → BCD → ABCD route to 11 -keto steroids is reported involving a high yield stereoselective intramolecular Diels-Alder reaction of furan-diene $\text{12}$ in water as a key-step. The dienophilic side chain is readily introduced starting from $\text{8}$ via a sequence involving alkylation with ethyl ($\text{E}$)-3-ethoxy-4-iodo-2-butenoate, reduction and acid hydrolysis. The reduced adduct $\text{14}$ is further converted into (±)-adrenosterone ($\text{6}$) via $\text{24}$, the dienediolate equivalent of which is a known intermediate in corticosteroid synthesis.     

The catabolism of phthalideisoquinoline alkaloids

Fumariflorine ($\text{1a}$, the only known alkaloidal $\text{o}$-(β-dimethylaminoethyl)benzoic acid, has been isolated as its ethyl ester $\text{1}$ from $\text{Fumaria}$$\text{parviflora}$ Lam. (Fumariaceae). Since alkaloids $\text{2}$–$\text{6}$ are also present in the plant, it is probable that the biogenetic sequence for the catabolism of the lactonic phthalideisoquinolines involves initial quatermination to an N-metho salt, Hofmann elimination, and oxidative cleavage of the resulting olefin to supply a substituted $\text{o}$-(β-dimethylaminoethyl)benzoic acid.     

The facile (<−50°C) formation of cis-bicyclo[6.1.0]nona-2,4,6-trienes from cyclonona-1,3,5,7-tetraenes: A symmetry - forbidden reaction

The formation of the $\text{cis}$-bicyclo [6.1.0] nona-2,4,6-trienes $\text{4a}$-$\text{c}$ is not due to the sequence $\text{1}$ → $\text{2}$ → $\text{4}$, which would involve the symmetry-forbidden reaction $\text{2}$ → $\text{4}$ even at ?50°C. Rather, reaction of RX at C^4–7 of $\text{5}$, which is formed together with $\text{1}$, leads (probably via $\text{6a}$-$\text{c}$ and $\text{7a}$-$\text{c}$ to $\text{4a}$-$\text{c}$.     

Cyclophane,XIV : darstellung polymethylierter [2.2]paracyclophane

Starting from 4, 5, 12, 13-tetrakis(methoxycarbonyl)[2.2]paracyclophane ($\text{1}$), the penta-($\text{4}$), hexa-($\text{6a}$–$\text{c}$), hepta-($\text{7}$), and octamethyl-($\text{8}$) derivatives have been prepared by a repetitive formylation-reduction sequence.     

Studies on the stereochemical course of intramolecular cycloaddition reactions of olefinic o-quinodimethanes-stereoselective synthesis of 8α, 9α, 14β-estranes

The stereoselective synthesis of 3-O-methyl-7α-$\text{p}$-toluenesulphonyl-8α, 9α, 14β-estradiol ($\text{25}$) and its 11-oxo derivative ($\text{26}$) $\text{via}$ thermolysis of 1β-$\text{tert}$-butoxy-2α-[2-(4-methoxybenzocyclobutenyl)ethyl]-2β-methy1-3α-[2-($\text{p}$-toluenesulphonyl)ethenyl] cyclopentane ($\text{22}$) and its oxo derivative ($\text{24}$), which were derived from condensation product ($\text{9}$) of optically active aldehyde ($\text{8}$) and 1-cyano-4-methoxybenzocyclobutene through $\text{10}$ and $\text{11}$ to selenides $\text{16}$ and $\text{21}$, is described.     

A quadratically convergent reference state optimization procedure

A quadratically convergent procedure for the optimization of multiconfigurational reference states is presented and analyzed. The optimal reference state is determined from the energy variation principle by means of a sequence of unitary transformations of the form exp(i$\text{Λ}$exp(i$\text{k}$, where the hermitean operators $\text{Λ}$ and $\text{k}$ generate transformations of orbitals and correlation coefficients, respectively. Sample calculations are carried out within the Pariser—Parr—Pople model using a correlated reference state suggested by Clementi and Veillard. For the systems considered so far, convergence is achieved after 2–4 transformations.     

Optical resolution of tricarbonyl(1-carboxycyclohexa-1,3-diene) iron and the absolute configuration of the products

Resolution of the acid ($\text{1}$) (shown as the (+)-isomer) into its optically pure (+) and (?) isomers and reduction of the CO₂H yields the 2-Me derivative ($\text{2}$) (shown as the (?)-isomer). The absolute configuration of ($\text{2}$) is defined by conversion of the salt ($\text{3}$) of known configuration into ($\text{2}$) and ($\text{4}$). This is the first resolution leading to preparation of pure complexes of known absolute configuration.     

Total synthesis of (±)-Δ9(12)-capnellene via iterative intramolecular type-I-“Magnesium-ene” reactions

The marine triquinane sesquiterpene Δ⁹(¹²)-capnellene ($\text{1}$) was synthesised from 2,2,5-trimethyl-5-hexenal ($\text{2}$) by a sequence of all synthetic operations in 5% overall yield. The key steps 3 → 4 → 5 → 6 involve two intramolecular type-I-“Mg-ene” processes.     

Structural studies on a novel reaction product of malononitrile with aβb,δ-unsaturated allene aldehyde

Condensation of 2,5,5-trimethylhexa-2,3-dien-6-a1 with malononitrile affords an unexpected product, C₁₅H₁₆N_4X, ($\text{3}$), the structure of which was partially characterized by spectral (infrared, ultraviolet, ¹H, and ¹³C nmr) methods and fully elucidated by single crystal X-ray analysis. $\text{3}$ is l-cyano-2-amino-3-(2-propenyl)-5,5-dimethy-6- dicyanomethycycohexa-l,3-diene in a half-chair conformation. Conjugation of the $\text{cis}$-aminocyanoethenyl moiety leads to intermolecular

hydrogen bonding in the crystal. A reaction sequence and its mechanistic implications are proposed.     

Studies on organophosphorus compounds—XXXVI: Simple new routes to phosphorins from 2-hydroxy-, 2-mercapto-, and 2-aminobenzoic acids and their derivatives

2-Hydroxybenzoic acid heated with 2,4 - bis(4 - methoxyphenyl) - 1,3,2,4 - dithiadiphosphetane - 2,4 -disulfide, 1, gave 2 - (p - methoxyphenyl) - 4$\text{H}$ - 1,3,2 - benzoxathiaphosphorin - 4 - one 2 - sulfide, 3, and its thio-analogue, 4, while its ethyl or phenyl esters gave 4 as the sole product. 2 - Mercaptobenzoic acid and its ethyl ester when heated with 1 produced 3$\text{H}$ - 1,2 - benzodithiole - 3 - one, 8, 3$\text{H}$ -1,2 - benzodithiole - 3 - thione, 9, and 2- (p - methoxyphenyl) - 4$\text{H}$ - 1,3,2 - benzodithia - phosphorin - 4 - one 2 - sulfide, 10. The reaction of 2 -aminobenzoic acid with 1 gave 1,2 - dihydro - 2 - (p - methoxyphenyl) - 4$\text{H}$ - 3,1,2 - benzoxaphosphorin - 4 - one 2 - sulfide, 12. Reactions of 1 with methyl 2 - aminobenzoate and 2 - aminobenzamides are described. Mechanistic considerations for the formation of the heterocyclic phosphorus compounds are presented.     

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.     

Cycloaddition of diphenylnitrilimine to coumarins. The synthesis of 3a,9b-dihydro-4-oxo-1H-benzopyrano [4 ,3-c]pyrazole derivatives

The cycloaddition of diphenylnitrilimine to a series of coumarins occurs with the same regioselectivity in all cases, regardless the nature of the substituent present, to yield the corresponding 3a,9b-dihydro-4-oxo-lH-benzopyrano [4,3-c]pyrazoles $\text{4}$a–f. Dehydrogenation of $\text{4a}$ yields 4-oxo-1H-benzopyrano [4,3-c]-pyrazole $\text{6}$. In ethanolic sodium ethoxide solution, the reaction between coumarin and diphenylnitrilimine precursor, namely N-phenylbenzohydrazidoyl chloride $\text{1}$, affords no cycloadducts, but yields o-(β-ethoxycarbonylvinyl)phenyl N-phenylbenzohydrazidate $\text{10}$. The regiochemistry of the cycloadducts $\text{4}$a–f and the reaction sequence leading to $\text{10}$ are outlined. The structures of the products have been established by spectroscopic methods and independent syntheses wherever possible.     

Synthesis of trans-1,2-diphenyl-3,4-bis[4-(2,6-diphenyl-4H- pyranylidenyl)]cyclobutane: correction and structure proof

The reaction of phenyl lithium acetylide ($\text{2}$) with 2,6-diphenylpyrylium perchlorate ($\text{1}$) is solvent dependent. With diethyl ether as solvent, the isolated product differed from that previously reported and is reassingned as 2,6-diphenyl-4-phenylacetylenyl-4$\text{H}$-pyran ($\text{5}$). On the other hand, in THF the title compound ($\text{6}$) was obtained; its structure confirmed by single-crystal x-ray crystallography.     

A Wittig reaction on mucochloric and mucobromic acids. Preparation of ethyl (2E, 4Z -4,5-dihalo-2,4-pentadienoates and alkyl 2E -5-bromo-2-penten-4-ynoates

Reaction of mucochloric and mucobromic acid with (ethoxycarbonylmethylene) triphenyl-phosphorane affords the ethyl ester of (2$\text{E}$, 4$\text{Z}$ -4,5-dichloro- and (2$\text{E}$, 4$\text{Z}$) -4, 5-dibromo-2,4-pentadienoic acid respectively; in the latter case ethyl (2$\text{E}$ -5-bromo-2-penten-4-ynoate is formed concomittantly.     

Pheromone XXXVII. Eine stereospezifische synthese der komponenten des sexualpheromons von antherea polyphemus, (E)-6,(Z)-11-hexadecadienylacetat und (E)-6,(Z)-11-hexadecadienal.

Starting from the aldehydes $\text{2}$ and $\text{9}$ the acetylene $\text{16}$ is prepared via the borane $\text{15}$ by means of a combined Wittig reaction-hydroboration reaction sequence. $\text{16}$ may be converted into the (E)-6,(Z)-11-hexadecadienylacetate ($\text{18}$) and the corresponding aldehyde $\text{19}$. The synthetic route proceeds with high stereospecifity (isomeric purity of $\text{18}$ and $\text{19}$ ? 97%).