乾燥したオオキンケイギク花弁中から7,3',4'-トリヒドロキシ-8-メトキシフラバノンの単離に成功した。この化合物は高い抗酸化活性を有していた。ピロガロールを出発物質にα-ジメチルホスホノ‐2-ヒドロキシアセトフェノン類を調製した。THF溶媒中DBUなどの有機塩基存在下、各種アルデヒドと反応させ、対応するカルコン誘導体を合成した後、フラバノン誘導体への変換を検討した。

平成15年度文部科学省サイエンス・パートナーシッププログラム採択事業についての研究成果を報告した。 動機付け教育として実験、実習が効果的であり、生徒・学生の学習活動が継続的に行なわれれば、自学自習によって高度な教育が可能であることが示唆された。同時に実験・実習内容の精査やプログラム以前での実験技術に拘わる事前実習やティーティングアシスタントの養成が重要であることを指摘した。

In the transition metal complex catalyzed asymmetric synthesis, one of the most important needs is the development of effective chiral ligands. We describe here the synthesis of a bulky type of 2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene bearing carboxyl group. Reaction of 1 with methyl acrylate gave an isomer mixture of 2a-d in 94% yield. Recrystallization of the mixture from ethyl acetate-hexane gave a pure 2b as a first crystal. Recycling preparative HPLC of the filtrate with CHCl_3 was succeeded to separate 2a. Reduction of 2b with HSiCl_3 and subsequent alkaline hydrolysis gave (±)-2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene-12(anti)-carboxylic acid (3b) in 43% yield. Resolution of (±)-3b with (-)-α-methylbenzyl-amine was succeeded to give an optically pure (-)-3b, [α]_D^<23>=-37.55 (c 0.39, CHCl_3). The reaction of triethyl sodiophosphonoacetate with 2-cyclohexenyl acetate in the presence of Pd(OAc)_2・(-)-3b (1.5 mol%) gave the allylic alkylation product in 96% (53%ee). On the other hand, many compounds containing thiazolidinedione moiety such as rosiglitazone and pioglitazone have been useful as the medicine. However, the convenient synthesis of thiazolidine derivatives having phosphorus functional group has been rarely reported, to our knowledge. We now report the synthesis and synthetic application of 5-(diethylphosphono)-1,3-thiazolidine derivatives. Treatment of triethyl phosphonoacetate with sodium hydride and powdered sulfur generated thiolate anion intermediate. And subsequent reaction with phenyl isocyanate (4a) gave thiocarbamate 5a in 40% yield. While similar reaction with benzyl isocyanate (4b) gave 3-benzyl-5-(diethylphosphono)-1,3-thiazolidinedione (6b) in 8% yield together with thiocarbamate 5b in 25% yield.

The target molecules of this research projects are novel organic electron donors (1) and acceptors (2,3,4), which are expected to act as effective components to form charge-transfer complexes exhibiting high electric conductivities. The molecule, 1, carries two 7π electron rings fused to a naphthalenene at its two peri-positions and is expected to behave as a good electron donor in the two stage redox processes. Synthesis of 1 is started from acenaphthene. It was transformed to 1,8-Bis (dibromomethyl)-4,5-dichloronaphthalene by 5 reaction steps. The dibromide was reacted with cis-4,5-bis (boryl) octene, prepared from bis [pinacolato] diboron and 4-octyne, to yield a pleiadene derivative. However, the yield was very low and not improved by modification of reaction conditions. Then we have adopted the intramolecular Friedel-Crafts type reaction for construction of the 7-membered ring. We have synthesized acepleiadiene (5, R=H) and acepleiadylene (6, R=H) by the latter method and found 5(R=H) showed a comparable 1^ oxidation peak as that of TTF by CV measurement. Efforts to obtain 1(R=H) via pleiadiene are in progress. Tellurophene-TCNQs (2, n=1, R=H) are only ones left unknown among Hetero-TCNQs, Synthesis of 2 is started from tellurophene. It was converted to 2,5-bis (hydroxymethyl) derivative via 3 reaction steps. Transformation of hydroxymethyl group to dicyanomethylene group to obtain 2 (n=1, R=H) is now actively sudying. Chrysene-TCNQ and -quinone (3) have a unique extended conjugated π-system and are expected to be very stable and have very low coulombic repulsion in their oxidation states. Its synthetic plan through a key intermediate, 2,8- dimethoxychrysene, was progressed. The key compound was obtained in a fairly short steps of reaction and its conversion to 3 is now scrutinized. Phenanthrene-TCNQ and -quinone (4) are unique and assumed to be a strong acceptor, because they have a oquinoid partial structure. Its synthetic plan via 3,6-dibromo- or 3,6-dimethoxy-phenanthrene was executed with success. Both key intermediates were obtained in good yields from the corresponding biphenyls. A green solid compound, which has a very low solubility to common organic solvents, appeared to be 4 (R=C(CN)_2) was obtained by the two successive reactions, substitution of bromine of the former key compound with dicyanomethyl anion and oxidation, We are now actively studying its structure and properties. JA01K

Recently, the rhodium(II)-catalyzed intramolecular C-H insertion of α-diazo carbonyl compounds has been widely studied and found to be great of value. Reported herein is the synthesis of α-phosphonocyclobutanones bearing 9,10-dihydro-9,10-ethanoanthracene moiety via rhodium(II)-catalyzed intramolecular insertion reaction. 11-Methyl- (3b), 11-ethyl- (3c), and 11-propyl-11-(dimethylphosphono)-acetyl-9,10-dihydro-9,10-ethanoanthracene (3d) were prepared from the Diels-Alder adducts of anthracene and methyl acrylate derivatives, and dimethyl lithiomethylphosphonate in good yields. Α-Diazo β-keto phosphonates 4b-d were readily prepared from 3b-d according to the conventional diazo transfer method by the use of p-toluenesulfonyl azide. Catalytic decomposition of f4b-d was carried out in ClCHィイD22ィエD2CHィイD22ィエD2Cl containing RhィイD22ィエD2(Oac)ィイD24ィエD2 at 80℃ to afford the mixture of cyclobutanones 5b-d and cyclopentanones 6c,d. The stereochemical assignment of 7,8 : 9,10-dibenzo-2-ethyl-4-(dimethylphosphono)tricyclo[4.2.2.0ィイD22,5ィエD2]deca-7,9-dien-3-one (5c) was made on the basis of their ィイD11ィエD1H NMR and IR spectral data. That is, the IR spectrum of 5c shows a peak for carbonyl absorption at 1774.7 cmィイD1-1ィエD1. The ィイD11ィエD1H NMR spectrum of 5c shows a signal for methyl (t, J=4.9 HィイD2ZィエD2, 3H) at δ1.09 and a signal for methine (d, J=3.9 HィイD2ZィエD2, 1H) of 6-position at δ4.51. Accordingly, cyclobutanones were exclusively produced via insertion into the ethane bridge methylene C-H bonds. A similar decomposition of 4b-d with chiral Rh(II) catalysts, such as RhィイD22ィエD2[N-Phtn-(L)-Phe]ィイD24ィエD2 and RhィイD22ィエD2[N-Phth-(L)-Ala]ィイD24ィエD2, afforded the desired optically active 5b-d up to 43%ee. In this reaction, the use of RhィイD22ィエD2[N-Phth-(L)-Phe]ィイD24ィエD2 gave the optically active 5b-d in higher optical yield than that of RhィイD22ィエD2[N-Phth-(L)-Ala]ィイD24ィエD2 irrespective of the kind of alkyl substituents at 11-position of diazo compounds 4b-d.

The target molecules of this research projects are novel organic electron donors (1) and acceptors (2, 3, 4), which are expected to act as effective components to form charge-transfer complexes exhibiting high electric conductivities. The molecule, 1, carries two 7pi electron rings fused to a naplithalenene at its two peri-positions and is expected to behave as a good electron donor in the two stage redox processes. Synthesis of 1 is started from acenaphthene and are first dichiorinated its peri-positins then transformed its 5-membered ring to a cyclic anhydride via bromination with NBS and the following oxidation. The diol obtained by LAH reduction of the anhydride was transformed to 1, 8-Bis(dibromomethyl)4, 5-dichioronaphthalene. The dibromide was reacted with cis-4, 5-bis(boryl)octene, prepared from bis[pinacolato]diboron and 4-octyne, to yield a pleiadene. Efforts to obtain 1 (R=n-Pr) in progress. Tellurophene-TCNQs (2) are only ones left unknown amoung Hetero-TCNQs. Synthesis of 2 is started from tellurophene, which is prepared by 1,4-bis(TMS)-1, 3-butadiyne and Na_2Te and then converted to 2, 5-dicarboxylic acid via 6 steps. Transformation of carboxyl group to dicyanomethylene group to obtain 2 (xl, R=H) is now actively sudying. Crysene-TCNQ (3) has a unique extended conjugated pi-system and expected to be very stable and have very low coulombic repulsion in their oxidation states. Their synthesis are planned to couple a 2-bromo-6-methoxynaphthalene and 2-bromo-5-methoxybenzaldehyde by Suzuki-Miyaura method to yield a key intermediate to lead 2, 8-dimethoxyclirysene. The coupling reaction is now scrutinized. Phenanthrene-TCNQ (4) is unique and assumed to be a strong acceptor, because it has a oquinoid partial structure. Its synthesis is planned to execute via a biphenyl derivative, which is obtained from 2-bromo-5-methoxytoluene and N,N-diethy1-4-methoxybenzamide by a combination of Suzuki-Miyaura and Snieckus coupling methods. The biphenyl derivative is subjected to metalatation, intramnoleculari condensation followed dehydroxylic elimination to afford a key phenanthrene derivative, 3, 6-dimethoxyphenanthrene. Now we are actively investigating coupling reaction conditions and procedures to obtain the biphenyl derivatives. Although we do not yet have the target molecules in our hands, we are closely approaching our targets and very sure to be able to get them in near future.

本研究では、酸性修飾基としてカルボキシル基を有する新規鎖状光学活性モノホスフィン配位子の開発とそれらのパラジウム錯体触媒を用いた不斉アリリックアルキル化反応への利用について行なった。鎖状光学活性モノホスフィンカルボン酸配位子の合成は次のように行なった。クロトン酸tert-ブチル、4-メチル-2-ペンテン酸tert-ブチル等のα,β-不飽和カルボン酸エステルにTHF溶媒中、n-ブチルリチウム及びHMPA存在下、ジフェニルホスフィンを1,4-付加させ、対応する3-(ジフェニルホスフィノ)ブタン酸tert-ブチル、3-(ジフェニルホスフィノ)-4-メチルペンタン酸tert-ブチルをそれぞれ93%、69%の収率で得た。続いてエステルの酸分解を行ないラセミ体として3-(ジフェニルホスフィノ)ブタン酸(DPBA)、3-(ジフェニルホスフィノ)-4-メチルペンタン酸をそれぞれ71%、42%の収率で得た。得られたラセミ体は光学活性なフェニルエチルアミンを用いた優先晶出法により容易に光学分割できた。この光学活性モノホスフィンカルボン酸配位子と酢酸パラジウムより系中でパラジウム錯体を調製し、酢酸シクロペンテニル、酢酸シクロヘキセニル、酢酸シクロヘプテニル、酢酸シクロオクテニル等の環状酢酸アリルとジエチルホスホノ酢酸エチルとの不斉アルキル化反応を行なった。その結果、従来の配位子と比較して非常に高い不斉収率でアルキル化反応が進行することを見い出した。さらに、環状アリル化合物の環サイズが増大するに従い、不斉収率も向上することが判明した。基質として酢酸シクロオクテニル、配位子にDPBAを用いた時に99%ee以上という最高の不斉収率を得た。

α位の典型金属のケイ素、ゲルマニウム、スズ等の官能基を導入したビニルホスホナ-トはビニルシラン、ビニルゲルマン及びビニルスタナンとしての特性とビニルホスホナ-トとしての特性の両反応性を兼ね備えているところから、極めて有用な試薬として期待されるにもかかわらず、未開拓の分野として残されていた。本研究では、 (1)β位にアルキルチオ基(1a,b)、アルコキシ基(1c)、アリール基(1d)等の官能基を有するビニルホスホナ-トを合成した。 (2)合成したビニルホスホナ-トと有機リチウム化合物から、α-リチオビニルホスホナ-トを調製した。続いてアルデヒドとのWittig-Horner反応より、β位にエタンジチオ基及びプロパンジチオ基を有するアレン中間体が生成し、さらにラジカル的な[2+2]シクロ付加反応によりシクロブタン化合物が立体特異的に得られた。 (3)α-リチオビニルホスホナ-トとトリオルガノメタルハライドとの反応により、α-(トリオルガノメタロ)ビニルホスホナ-トを高収率で合成することに成功した。 (4)ビニルシラン、ビニルゲルマンはアシルカチオンと反応して、α-アシルビニルホスホナ-トを高収率で与えた。 (5)α-シリル-β-エトキシビニルホスホナ-トは種々の求核試薬のマイケル付加反応を受け、その後EtO基の脱離を伴い、立体特異的にβ-置換α-(シリン)ビニルホスホナ-トを与えた。 (6)1aよりα-ヨードビニルホスホナ-トの合成に成功した。α-ヨードビニルホスホナ-トはPd触媒存在下、末端アセチレン類と温和な条件で容易に高収率でクロスカップリング生成物を与えた。 以上のごとく、本実験は初期の目的を果たすことに成功したと言える。