論文 - 門田 功
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A convenient and efficient route for the allylation of aromatic amines and alpha-aryl aldehydes with alkynes in the presence of a Pd(O)/PhCOOH combined catalyst system 査読
NT Patil, HY Wu, Kadota, I, Y Yamamoto
JOURNAL OF ORGANIC CHEMISTRY 69 ( 25 ) 8745 - 8750 2004年12月
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記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：AMER CHEMICAL SOC
The allylation of aromatic amines with alkynes proceeded smoothly in the presence of catalytic amounts of Pd(PPh3)(4) and benzoic acid. The allylation products were obtained in high yields in a regio- and stereoselective manner. The effect of various groups on the nitrogen atom of anilines was studied. Regardless of the substituent (electron withdrawing or electron donating) on the aromatic ring, the reaction proceeded well. Various functionalities, including -CH3, -OMe, -Cl, -CN, -COOMe, -NO2 and -COCH3 were tolerated under the reaction conditions. Similarly, the allylation of alpha-aryl aldehydes proceeded well with the same level of regio- and stereoselectivity as the allylation of aromatic amines. This reaction provides the second example of the transition metal catalyzed direct alpha-allylation of aldehydes.
DOI： 10.1021/jo0485684
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37(D-7) ブレベトキシンBの合成研究(口頭発表の部)
高村 浩由, 西井 広樹, 門田 功, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 46 ) 197 - 202 2004年10月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Brevetoxin B (1), a potent neurotoxin was isolated from the red tide organism Gymnodinium breve Davis in 1981. The unique structural features and biological activity of this molecule have attracted the attention of synthetic chemists. We have already reported the efficient method for the convergent synthesis of polycyclic ethers via the intramolecular allylation and subsequent ring-closing metathesis. Herein we report the convergent synthesis of the polycyclic framework of 1 based on our own methodology. The reaction of the bicyclic compound 12, prepared from the known compound 9, with the allylic silane 13 in the presence of TMSOTf gave the desired product 14, stereoselectively. The JK ring segment 6 was synthesized in 11 steps including one-carbon elongation from 14. Palladium-catalyzed coupling of the ketene acetal triflate 22, prepared from the known compound 18, and the organozinc reagent 23 gave the enol ether 24, which was converted to the BC ring segment 7. The connection of 7 and the FG ring segment 8 followed by several transformations afforded the allylic stannane 29. The partial reduction of 29 with DIBALH followed by trapping of the resulting aluminum hemiacetal with acetic anhydride provided the acetoxy ether 30. However, the yield was very low. Alternatively, the chlorosulfide 31, prepared from 26, was treated with the alcohol 8 in the presence of AgOTf to provide the O,S-acetal 32. Cyclization of 33 using AgOTf as a Lewis acid gave the desired product 34, stereoselectively. The construction of the E ring and the A ring via ring-closing metathesis afforded the ABCDEFG ring segment 5. The alcohol 5 and the carboxylic acid 6 were connected successfully by Yamaguchi conditions to give the ester 41. The construction of the polycyclic framework of 1 was performed via the intramolecular allylation and subsequent ring-closing metathesis to yield 46. Completion of the total synthesis of 1 is currently under way.
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26 ガンビエロールの合成研究(口頭発表の部)
高村 浩由, 大野 昭男, 佐藤 公美, 松田 久美子, 山本 嘉則, 門田 功
天然有機化合物討論会講演要旨集 ( 44 ) 151 - 156 2002年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Gambierol (1) is a marine polycyclic ether isolated as a toxic constituent from cultured cells of the ciguatera causative dinoflagellate, Gambierdiscus toxicus. This compound shows toxicity against mice (LD_<50>, 50μg/kg), and the symptoms resemble those caused by ciguatoxins. The unique structural features have attracted the attention of synthetic chemist. We have already succeeded in the convergent synthesis of the CDEFG ring system (8) via the intramolecular allylation of the α-acetoxy ether 4 and subsequent ring-closing metathesis. Encouraged by this result, we started the total synthetic study of gambierol (1). Treatment of the cyclization precursor 15, prepared from the ABC ring segment 10 and FGH ring fragment 11, with MgBr_2・OEt_2 gave the desired product 9 and its C16 epimer 16 in 22% and 47% yield, respectively. The yield of 9 was improved by using monochloroacetoxy group as a leaving moiety. Thus, the reaction of 19 gave 9 and 16 in 30% and 48% yield, respectively. The diene 9 was subjected to ring-closing metathesis with 7 to give 20 in 84% yield. The octacyclic compound 20 was converted to 28 by several steps. We next examined the construction of the triene side chain. Although the Stille coupling of 29 and 30 gave the cross-coupling product 31 in an allowable yield (63%), the reaction was very slow (4 days). After unfruitful attempts, we succeeded in developping an efficient method for the stereoselective synthesis of Z-iodoolefin 33. Treatment of 32 with Zn-Cu and AcOH gave 33 as a single stereoisomer in 80% yield. As expected, the reaction of 33 and 30 was very fast. The triene 31 was obtained in 95% yield after 1.5h. Similaly, the iodoolefin 35, prepared from 28, was converted to the fully protected gambierol 36 in good yield. The final deprotection of 36 giving 1 is currently under way.
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41 ポリ環状エーテルの収束的合成とガンビエロール全合成への応用(口頭発表の部)
門田 功, 大野 昭男, 高村 浩由, 佐藤 公美, 松田 久美子, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 43 ) 241 - 246 2001年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
A convergent synthesis of polycyclic ethers has been achieved by the intramolecular allylation of α-acetoxy ethers and subsequent ring-closing metathesis. The carboxylic acid 2 and alcohol 3 were connected by DCC coupling to give the ester 4 in 90% yield. After deprotection of the silyloxy group, the alcohol 5 was converted to the allylic stannane 8 via the mixed acetal 7 in good yield. The ester 8 was then subjected to the Rychnovsky protocol to give the α-acetoxy ether 9 as a mixture of diastereoisomers. The cyclization precursors 10-15 were prepared in a similar manner, and the results of the cyclization are summarized in Table 1. Treatment of 9 with 4 equiv of BF_3・OEt_2 gave a 70: 30 mixture of the cyclized products 16 and 17 in 79% yield (entry 1). Similarly, the cyclization of the substrates 10-15 proceeded stereoselectively to give the desired products in good yields (entries 2-7). We next examined the ring-closing metathesis of the products 18, 20, 22, 24, 25, and 27 (Table 2). Treatment of 18 with Grubbs catalyst 29 gave the tetracyclic ether 30 in 91% yield (entry 1). Similarly, the reactions of 20, 22, and 24 proceeded smoothly to afford the corresponding polycyclic ethers 31-33 in good yields (entries 2-4). Although the reactions of 25 and 27 with 29 were unsatisfactory, the use of the more active catalyst 34 provided the desired pentacyclic ethers 35 and 36 in high yield (entries 5 and 6). Based on these results, we have started the convergent synthesis of gambierol 1 and have synthesized the ABC and FGH ring segments, 48 and 60, from 2-deoxy-D-robose as shown in Schemes 2 and 3, respectively. Further studies toward the total synthesis of gambierol are now in progress in our laboratories.
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38 Gambierolの合成研究(口頭発表の部)
門田 功, 門脇 千恵, 朴 哲弘, 大野 昭男, 大高 学, 小黒 奈央, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 40 ) 223 - 228 1998年8月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Since 1981, a number of polycyclic ethers have been isolated from marine dinoflagellates. Much attention has been paid to the synthesis of these compounds due to their unusual structures, biological activities, and the rarity in nature. Gambierol, which has a 6,6,6,6,7,6,6,7-polycyclic ether skeleton including 18 stereocenters and a triene side chain, was isolated from the cultured cells of Gambierdiscus toxicus by Yasumoto in 1993. The compound shows toxicity against mice (LD_<50> 50μg/kg), and the symptoms resemble those caused by ciguatoxins inferring the possibility that it is also implicated in ciguatera poisoning. We now report the stereocontrolled construction of the AB, E, and H ring systems of Gambierol as parts of its total synthetic study. First, synthesis of the AB ring system of gambierol was achieved from 2-deoxy-D-ribose. The key steps were the stereoselective allylation of the aldehyde 2, corresponding to the B ring, and the intramolecular hetero-Michael reaction of 5. Next, the synthesis of the E ring was accomplished from D-ribose via the intramolecular reaction of allylic stannane 24 as a key step. The undesired stereoisomer 26 formed in this reaction was converted to the desired product 33 by using DBU mediated isomerization. Finally, stereoselective synthesis of the H ring was achieved from 2-deoxy-D-ribose by using the intramolecular reaction of allylic stannane 43 as a key step. Modified Stille coupling was successfully applied for the construction of the triene side chain to give 57.
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119(P62) ポリ環状エーテルの立体選択的合成とその応用(ポスター発表の部)
門田 功, 朴 正烈, 佐谷 志保子, 川田 美穂, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 38 ) 709 - 714 1996年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
The synthetic reaction using functionalized allylstannanes is widely appreciated as one of the most useful methods for the stereocontrolled C-C bond formation. We now report the stereoselective synthesis of functionalized heterocycles via the intramolecular reaction of allylstannane with aldehyde and imine. Stereocontrolled Total Synthesis of Hemibrevetoxin B The treatment of 6 with BF_3・OEt_2 gave 7 as a sole product. Similarly, the intramolecular reaction of 13 derived from 7 proceeded smoothly to give 14. The obtained tetracycle 14 was transformed to hemibrevetoxin B (1) by several steps. Intramolecular Reaction of Imine Derivatives To extend our methodology, we next examined the intramolecular reaction with imine, because the allylation of imine has been well studied as well as that of aldehyde, and such transformation would be an efficient method for the synthesis of cyclic amine derivatives. After several fruitless attempts, we found hydrazones are suitable as a carbon-nitrogen double bond functional group for the intramolecular reaction. The Lewis acid mediated reactions of 16 and 17 gave trans isomers 18a and 19a as a sole product in high to good yields. Stereoselective Synthesis of Hydroxylated Piperidine and Pyrrolidine Derivatives The structural framework of hydroxylated nitrogen heterocycle is widely found in naturally occurring piperidine/pyrrolidine alkaloids such as (-)-desoxoprosophilline and (+)-preussin. We examined the stereoselective synthesis of β-hydroxypiperidine and pyrrolidine derivatives via the intramolecular reaction of 20 and 22. To the best of our knowledge, this is the first example of a successful use of γ-aminoallylstannane in organic synthesis.
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Total synthesis of hemibrevetoxin B via the allylic tin methodology
Isao Kadota, Yoshinori Yamamoto
Main Group Metal Chemistry 19 ( 6 ) 361 - 366 1996年
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記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Walter de Gruyter GmbH
The total synthesis of Hemibrevetoxin B is described. A new cyclization approach, based on the Lewis acid mediated intramolecular cyclization of the γ-oxo-substituted allylic tin having an aldehyde group, produced the 6-6-7-7 polycyclic ether skeleton of the natural product with high stereoselectivity. The 1H and 13C-NMR spectra of synthetic hemibrevetoxin B was identical with those of natural product.
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24 ヘミブレベトキシンBの全合成(口頭発表の部)
門田 功, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 37 ) 139 - 143 1995年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Hemibrevetoxin B (1), isolated from cultured cells of the red tide organism Gymnodinium breve by Prasad and Shimizu in 1989, has a 6,6,7,7-tetracyclic ether skeleton and contains 10 stereocenters. Much attention has been paid to the synthesis of polycyclic ethers including hemibrevetoxin B owing to their unusual structural framework, novel functionalities, and biological activities. Recently, Nicolaou and coworkers have reported the first total synthesis of hemibrevetoxin B. We have reported stereocontrolled synthesis of the 6,6,7,7-tetracyclic ether skeleton of 1 via the intramolecular allylic tin-aldehyde (and ketone) condensation. Chain elongation to the left-hand side aldehyde from this intermediate was difficult, and therefore we utilized 2 having hydroxypropyl side chain as a starting material. The total synthesis of 1 has been accomplished via the allylic tin methodology. The 6,6-ring system 11 prepared via the modified Nicolaou method was converted to 18. Cyclization of 18 with BF_3・OEt_2, proceeded quite smoothly and stereoselectively to give 19 in 94% yield. No diastereoisomers were detected in the cyclization step. The BF_3・OEt_2 mediated cyclization of 25 prepared from 19 by usual transformation provided the 6,6,7,7 system 26 as a single stereoisomer. Oxidation followed by Grignard reaction gave methyl carbinol derivative as a 1:1 mixture of diasteroisomers. After silyl protection, the desired isomer 27 was isolated by column chromatography. Diene side chain was introduced by Wittig olefination followed by elimination to give 30. Construction of the α-methylene aldehyde moiety was achieved by Mannich reaction with Eschenmoser's salt. ^1H and ^<13>C-NMR spectra of synthetic hemibrevetoxin B(1) was identical with those of natural product.
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11 14族有機金属化合物を用いる新規環化反応の開発とポリエーテル系天然物合成への応用(口頭発表の部)
門田 功, Gevorgan V., 山田 順一, 山本 嘉則
天然有機化合物討論会講演要旨集 ( 33 ) 78 - 85 1991年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Recently, we have developed a novel and efficient method for the synthesis of β-alkoxy cyclic ethers. This methodology is based on the intramolecular reaction of the group 14 organometallics with acetals or aldehydes. Thus, treatment of γ-alkoxyallylsilane 1 with TiCl_4-PPh_3 afforded 6-membered cyclic ether 2a as a major product along with small amounts of its cis isomer 2b (95% total yield, trans:cis=98:2). Furthermore, this cyclization reaction was applicable for the synthesis of 7- and 8- membered cyclic ethers (Table II, Scheme 1). As a next stage, we carried out the construction of 6-7-7-6 fuzed ring system 16 which is the CDEF ring skeleton of brevetoxin B(Scheme 2, 3, 4). The BF_3・OEt_2 promoted reaction of 23 derived from optically active diol 17 gave 24 in 99% yield without accompaning the formation of any other stereoisomers. The most attractive aspect of the present procedure was iterative ring construction; the repeated use of the allic tin based cyclization gave 16 in good yield.
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64(P1-12) キラルなトリフレート誘導体を用いる光学活性天然物の合成(ポスター発表の部)
小槻 日吉三, 門田 功, 越智 雅光
天然有機化合物討論会講演要旨集 ( 31 ) 490 - 497 1989年9月
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記述言語：日本語 出版者・発行元：天然有機化合物討論会
Recently, we have developed a new and efficient method for the carbon-carbon bond forming reaction by using copper(I)-catalyzed Grignard reagents with triflates, which bear a β-oxygen fuctionality. Since those starting triflates are readily accessible from simple chiral building blocks, the procedure provides a very convenient approach to synthesize a variety of natural products in optically active forms. As an application of this methodology, we have accomplished the enantioselective syntheses of (+)-exo-brevicomin (7), one of the aggregation pheromones of bark beetles, and (5R,6S)-(-)-6-acetoxy-5-hexadecanolide (16), a major oviposition attractant pheromone of the mosquito Culex pipiens fatigans, via tosyl-triflate 6 as a common key intermediate. In both examples the use of 6 has enabled us to realize the sequential C-C bond formation in one-pot operation and hence the overall yields were considerably improved. The similar strategy could be applied to the synthesis of naturally occurring hydroxy-γ-lactone 12 (termed L-factor). As an alternative pathway, the stepwise methods towards these target molecules were also examined.