Stereoselective Synthesis and Complexation of a New Chiral Hybrid Phosphine-Phosphine Oxide Ligand from (S)-(+)-Prolinol

Abstract

The synthesis and the complex formation of chiral heterotopic ligands with two different binding sites each capable of bonding a different type of metal are described. The action of bis(dimethylamino) aryl phosphine on (S)-(+)-prolinol gives rise to the kinetic stereoisomer (2S,4S)-2-phenyl-1,3,2-oxazaphospholidine 1 and the thermodynamic stereoisomer (2R,4S)-2-phenyl-1,3,2-oxazaphospholidine 2. 1 is then totally converted into 2 at the end of the reaction. The Michaelis Arbuzov reaction of 2 with benzylbromide affords (R_p)-benzylaryl-(2-(S)-bromomethyl pyrrolidine-1-yl) phosphine oxide 3 in 80% yield. Compound 3 is an ideal chiral precursor for the synthesis of chiral hybrid phosphine-phosphine oxide ligands. The bromide atom is smoothly displaced by lithium diphenylphosphide to afford in 80% yield (R_p)-benzylaryl-(2-(S)-diphenylphosphinomethylpyrrolidine-1-yl) phosphine oxide 5. These reaction are proved to be totally stereoselective : the Michaelis Arbuzov reaction does not change the configuration at C2 in the proline ring. The relative configuration (R_p) of 5 (aryl = phenyl) was determinated by X-ray diffraction, from the known configuration of (S)-(+)-prolinol.     

Hydride migration in the mass spectra of some 2-phenyl-1,3,2-dioxsilacycloalkanes

The mass spectra of a series of 2-phenyl-1,3,2-dioxasilacycloaklanes all contain a peak at $\text{m}\text{e}$ P–78, which we suggest arises from hydride migration from the ring.     

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.     

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.     

Preparation of five- and six- membered cyclic ketones by the palladium-catalyzed cyclization reaction. Application to methyl dihydrojasmonate synthesis

Methyl 3-oxo-8-phenoxy-6-octenoate ($\text{1}$) was cyclized using Pd(OAc)₂-PPh₃ as a catalyst to give 2-carbomethoxy-3-vinylcyclopentanone ($\text{2}$) and 2-carbomethoxy-4-cycloheptenone ($\text{3}$). The former was the main product in acetonitrile. 2-Alkylated 3-oxo-8-phenoxy-6-octenoates were converted mainly to the five-membered ketones. Based on this cyclization method, methyl dihydrojasmonate ($\text{8}$) was prepared from methyl 2-pentyl-3-oxo-8-phenoxy-6-octenoate ($\text{5}$). Methyl 3-oxo-9-phenoxy-7-nonenoate (10) was subjected to the palladium-catalyzed cyclization to afford 2-carbomethoxy-3-vinylcyclohexanone (11) selectively without forming the eight-membered ketone (12).     

X-ray crystallographic study of some pentacoordinated organogermanium compounds

The X-ray crystallographic structures of 2-(2-phenyl-5-oxo-1,3,2-oxathiagermolan-2-ylthio)acetic acid (2), its pyridinium salt (3), and the pyridinium salt of 2-(2-t-butyl-5-oxo-1,3,2-oxathiagermolan-2-ylthio)acetic acid (1), (4), together with 2-(2-phenyl-1,3,2-oxathiagermolan-2-ylthio)ethanol (5) were determined and compared with that of 1. All of compounds investigated, 2-5, have the TBP-like, pentacoordinated structure. This fact seems to indicate that the driving force of pentacoordination of this type of compounds is the existence of an oxygen atom δ to the germanium atom that readily forms a five membered ring by hypercoordination.     

New 1,1-amino hydroperoxides from regioselective oxygenation of 4-(n-arylmethyleneamino)-2,6-di-t-butylphenols.

The oxygenation of 4-(N-arylmethyleneamino)-2,6-di-$\text{t}$-butylphenols with Co(Salpr), a five coordinate Co(II0 Schiff base complex, in CH₂Cl₂ results in the regioselective hydroperoxylation at the imino carbon to give N-(l-aryl-l-hydroperoxymethyl)-3,5-di-$\text{t}$-butyl-$\text{p}$-benzoquinone monoimines, which give exclusively the corresponding amides and 2,6-di-$\text{t}$-butyl-$\text{p}$-benzoquinone in an aerobic solution of KOH in 90% EtOH.     

Calozeylanic acid,a new bark acid from three calophyllum species (guttiferae)

Calozeylanic acid has been isolated from the bark of three $\text{calophyllum}$ species: $\text{C.lankaensis}$ (= $\text{C.zeylanicum}$), $\text{C.thwaitesii}$ and $\text{C.walkeri}$. Its structure has been established as 2(R),3(R)-2,3-Dimetyl- 5-hydroxy-6-(3-methylbutanyl)-6-(3,7-dimethylocta-3,6-dienyl)-7-oxo-8- (2-carboxy-1-phenylethyl)-2,3,6,7-tetrahydrobenzo-4-pyrone.     

Boron-nitrogen compounds: XCVI. Studies of the chemical behavior of monomeric pyrazol-1-ylboranes

Two 1,3-dimethyl-2-(methylpyrazol-1′-yl)-1,3,2-diazaboracyclopentanes have been prepared. The interaction of such monomeric pyrazol-1-ylboranes containing trigonal boron with pyrazoles has been examined and $\text{1}\text{1}$ molar addition compounds have been identified and isolated. Labelling experiments support spectroscopic evidence to suggest a mobile bridging hydrogen in the cited adducts at ambient temperature and above. Monomeric 1,3-dimethyl-2-(pyrazol-1′-yl)-1,3,2-diazaboracyclopentane reacts with (dimethylamino)dialkylboranes by an exchange of the pyrazolyl with the dimethylamino group. A cyclic transition state involving a B₂N₃ ring system is suggested for this process in which the corresponding 2-dimethylamino-1,3,2-diazaboracyclopentane and B-tetraalkylpyrazaboles are the final products. The latter are also found among the reaction products of pyrazole adducts of monomeric pyrazol-1-ylboranes with (dimethylamino)dialkylboranes. The interaction of (dimethylamino)dialkylboranes with pyrazole gives B-tetraalkylpyrazaboles in essentially quantitative yield.     

Synthesis applications of aza-cope rearrangements.: Stereocontrolled synthesis of cyclohepta [b]pyroolidines1

Both $\text{cis}$- and $\text{trans}$-3a-aryl-4-oxo-decahydrocyclohepta[b]pyrroles can be prepared in stereocontrolled fashions by the reaction of 2-amino-1-(1-phenyl- vinyl)cyclohexanols with formaldehyde and acid.     

New developments in the synthesis of lower fluorinated pyridines via diazotization-fluorination of aminopyridines in anhydrous hydrogen fluoride

The isolation and stabilization of elusive 4-fluoropyridine as the hydrochloride salt (54% yield) from fluorodediazoniation of 4-aminopyridine in anhydrous hydrogen fluoride (AHF) is described. Unlike the low yields (0–13%) recently reported from the chlorodediazoniation of 2,6-diaminopyridine and 3-halo-2,6-diaminopyridine, fluorodediazoniation gave high yields (49–62%) of the corresponding 2,6-difluoropyridines. In contrast, benzene analogs, i.e. $\text{m}$-phenylenediamine and 4-chloro-$\text{m}$-phenylenediamine, form only tars under similar fluorination conditions. Vicinal aminohalopyridines, e.g. 3-amino-2-chloropyridine and 2-amino-3,5-dichloropyridine give the corresponding fluorohalopyridine in 49–89% yield. Again, the benzene analogs, i.e. $\text{o}$-chloroaniline and 2,4-dichloroaniline, resist fluorination.     

Oxygenation of 4-(N-alkylimino)methyl-2,6-di-t-butylphenols mediated by Co(II)-Schiff base complex

4-(N-Alkylimino)methyl-2,6-di-$\text{t}$-butylphenols ($\text{1}$), Schiff bases of 3,5-di-$\text{t}$-butyl-4-hydroxybenzaldehyde can be oxygenated in the presence of Co(Salpr), a five coordinate Co(II)-Schiff base complex to give N-alkyl-3-$\text{t}$-butyl-5-formyl-2-hydroxy-2-pivaloyl-1,2-dihydropyridines ($\text{2}$ as the main product together with 3-formyl-2,5-di-$\text{t}$-butyl-2,4-cyclopentadienone ($\text{3}$) and 2,6-di-$\text{t}$-butyl-4-formyl-6-hydroxy-4,5-epoxy-2-cyclohexenone ($\text{4}$). These products result from dioxygen incorporation into the ortho position of $\text{1}$.     

Generation and reactivity of bis(2,6-diethylphenyl)germanium(II)

The title intermediate ($\text{3a}$) is produced on photolysis of hexakis(2,6-diethyl-phenyl)cyclotrigermane ($\text{1}$) or bis(2,6-diethylphenyl)bis(trimethylsilyl)germane ($\text{4}$) as evidenced by trapping experiments, and thermally dimerizes to tetrakis(2,6-diethyl-phenyl)digermene ($\text{2a}$). Diarylgermylenes such as $\text{3a}$ do not form stable triethylamine adducts (e.g. $\text{5a}$) as has been previously reported.     

Halofluorination. Part II. bromofluorination of arylcyclohexenes

Bromofluorination of 1-phenylcyclohexene with N-bromosuccinimide-hydrogen fluoride-pyridine in ether proceeds with Markovnikov-type regioselectivity. The reaction is stereospecific anti. Bromofluorination of 2-phenyl-3-bromocyclohexene results in the formation of $\text{r}$-1-bromo, $\text{t}$-2-fluoro-2-phenyl, $\text{t}$-3-bromocyclohexane.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Inept-29Si NMR study of a TiCl4-mediated reaction of an enol silyl ether

Condensation of 1,3-bis(trimethylsiloxy)-1-methoxybutadiene ($\text{1}$) and 2-phenyl-2,2-dimethoxyethanal ($\text{2}$) under TiCl₄ condition gave the γ-hydroxycyclopentenone product $\text{3}$. The reaction was followed by INEPT²⁹Si NMR. Implication to the mechanism of the reaction was discussed.     

A 1,2-phenyl shift to the double bond of a vinyl cation

Reaction of HCl with 3-phenylpropyne ($\text{1}$) afforded 1,2-dichloro-2- phenylpropane($\text{6}$) among other products. The reaction proceeds by a 1,2-phenyl shift to the 5-phenyl-1-propene-2-yl cation ($\text{2}$).     

A revised structure for hermonionic acid

Hermonionic acid and its decarboxylated product have been isolated from $\text{Garcinia}$$\text{quaesita}$. ¹³C NMR spectral and chemical evidence indicate that hermonionic acid is 2-0-[2-(3-methylbut-2-enyl)-3-methoxy- 4-hydroxy-5-(3,7-dimethylocta-2,6-dienyl]-4-methoxy-5-(3-methylbut-2-enyl-6-hydroxybenzoic acid. The previously assigned dienone structure for this acid is incorrect.     

Stekeospecific transformation of D-sugar to L-sugar in complex aminoglycoside. Synthesis of a kanamycin B analog having 2,6-diamino-2,4,6-trideoxy-L-arabino-hexopyranose

A 4′-ene derivative of kanamycin B ($\text{4}$) was derived from the epoxide ($\text{1}$) by oxidative elimination of the 4′-phenylseleno group into the allylic alcohol ($\text{3}$). The title compound, 0-(2,6-diamino-2,4,6-trideoxy-β-L-arabino-hexopyranosyl)-(1→4)-0-[3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)]-2-deoxystreptamine ($\text{6}$) was obtained from $\text{4}$ by stereospecific hydrogenation followed by removal of the masking groups, changing the D-sugar moiety of the 4-0-glycoside portion into an L-sugar.