JP4064645B2 - New production method of polysubstituted cycloalkenes - Google Patents

Description

（式中、Ｒ^１は、置換基を有していても良いアルキル基、置換基を有していても良いアリール基又は置換基を有していても良いアラルキル基を表す。）
で示される化合物が挙げられる。
【０００６】
本発明の製造法において用いられる、ケト基を有するα，β−不飽和化合物としては、例えば下記一般式［２］
【化５】

（式中、Ｒ^２は、置換基を有していても良いアルキル基、置換基を有していても良いアリール基又は置換基を有していても良いアラルキル基を表し、Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６，Ｒ^７，Ｒ^８，Ｒ^９及びＲ^１０はそれぞれ独立して水素原子、置換基を有していても良いアルキル基、置換基を有していても良いアリール基又は置換基を有していても良いアラルキル基を表す。また、Ｒ^６とＲ^８又はＲ^８とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になって芳香環若しくはシクロアルキル環を形成していても良く、更には、Ｒ^２とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になってシクロアルキル環を形成していても良い。Ｘは電子吸引性の官能基を表し、ｍ及びｎはそれぞれ独立して０又は１を表す。）
で示される化合物が挙げられる。
なお、上記一般式［２］で表されるアルケンの立体構造はシスでもトランスでもどちらでも良い。
【０００７】
本発明の製造法により得られる多置換シクロアルケン類としては、例えば下記一般式［３］
【化６】

（式中、Ｒ^１〜Ｒ^１０、Ｘ、ｍ及びｎは前記と同じ。）
で示される化合物が挙げられる。
【０００８】
上記一般式［１］〜［３］において、Ｒ^１〜Ｒ^１０で表される、置換基を有していても良いアルキル基のアルキル基としては、例えば、炭素数が１〜２０、好ましくは１〜１０、より好ましくは１〜６の直鎖状、分枝状又は環状のアルキル基が挙げられ、より具体的には、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、第二級ブチル基、第三級ブチル基、ペンチル基、ヘキシル基、シクロプロピル基、シクロペンチル基、シクロヘキシル基等が挙げられる。
また、置換基を有していても良いアリール基のアリール基としては、例えば、炭素数６〜３０、好ましくは６〜２０、より好ましくは６〜１４の単環、多環又は縮合環式の芳香族炭化水素基が挙げられ、より具体的には、例えば、フェニル基、トリル基、キシリル基、ナフチル基、メチルナフチル基、アントリル基、フェナントリル基、ビフェニル基等が挙げられる。
置換基を有していても良いアラルキル基のアラルキル基としては、例えば、炭素数７〜３０、好ましくは７〜２０、より好ましくは７〜１５の単環、多環又は縮合環式のアラルキル基が挙げられ、より具体的には、例えば、ベンジル基、フェネチル基、ナフチルメチル基、ナフチルエチル基等が挙げられる。
また、これらアルキル基、アリール基、アラルキル基の置換基としては、本発明に係る反応の進行に支障を来さないものであればどのような置換基でも良いが、例えば、アルケニル基、アルキニル基、アルコシ基、ハロゲン原子等が挙げられる。
【０００９】
上記一般式［２］及び［３］において、Ｘで表される電子吸引性の官能基としては、例えば、−ＣＯＯＲ基、−ＣＨ＝ＮＲ基、−ＣＮ基、−ＳＯ_２Ｒ基（但し、Ｒは、何れの場合も、水素原子、アルキル基、アリール基又はアラルキル基を表す。）等が挙げられ、−ＣＯＯＲ基が特に好ましい。
ここで、Ｒで表されるアルキル基、アリール基、アラルキル基としては、上記した、Ｒ^１〜Ｒ^１０で表されるアルキル基、アリール基、アラルキル基のそれと同じものが挙げられる。
【００１０】
本発明の製造法において用いられるイノラートアニオンは、例えば下記反応スキームに従って容易に合成することが出来る。Tetrahedron 1998,43,2411-2422
【化７】

【００１１】
即ち、例えば、α，α−ジブロモエステルにターシャリーブチルリチウム（４当量）を加え、−７８度で３時間、更に０度で３０分反応させることにより合成できる。反応は通常、テトラヒドロフラン（ＴＨＦ）、ジエチルエーテル、ジイソプロピルエーテル等のエーテル系溶媒中で行われる。
【００１２】
本発明の多置換シクロアルケン類の製造法において、イノラートアニオンと、ケト基を有するα，β−不飽和化合物とのタンデム型環化付加−マイケル反応は、通常−４０度〜−７８度の間、好ましくは−７８度により近い温度で行われる。反応時間は通常１０分〜１時間程度であるが、３０分位が一般的である。反応は通常、テトラヒドロフラン（ＴＨＦ）、ジエチルエーテル、ジイソプロピルエーテル等のエーテル系溶媒中で行われる。
なお、α，α−ジブロモエステルからイノラートを合成する反応と、生成したイノラートと、ケト基を有するα，β−不飽和化合物とのタンデム型環化付加−マイケル反応は、通常ワンポットで行われる。
タンデム型環化付加−マイケル反応後の脱炭酸反応は、通常、酸触媒存在下加熱還流させることにより行われる。酸としては、酸性シリカゲル、塩酸、硫酸が適しているが、一般的には酸性シリカゲルが用いられる。溶媒はベンゼンかトルエンが一般的である。反応時間は１〜１０時間程度である。
【００１３】
本発明の製造法を比較的構造の簡単な化合物を例にして反応スキームで示すと大略下記の如くなる。
【化８】

【００１４】
また、一般式［２］において、Ｒ^２とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になってシクロアルキル環を形成している場合について、本発明の製造法を反応スキームで示すと下記の如くなる。
【化９】

【００１５】
更に、一般式［２］において、Ｒ^６とＲ^８又はＲ^８とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になって芳香環を形成している場合について、本発明の製造法を反応スキームで示すと下記の如くなる。
【化１０】

【００１６】
【実施例】
以下、実施例により本発明を更に具体的に説明するが、本発明はこれら実施例により何ら限定されるものではない。
【００１７】
実施例１ エチル（２，３−ジメチル−２−シクロペンテニル）アセテートの合成
２，２−ジブロモプロピオン酸エチル（２６０ｍｇ）のＴＨＦ溶液６ｍｌに−７８度冷却下、ターシャリーブチルリチウムのペンタン溶液（２．８２ｍｌ，１．４Ｍ）を加え、３時間撹拌、引き続き０度で３０分間撹拌した。次に−７８度に冷却し、６−オキソ−２−ヘプテン酸エチル（１３６ｍｇ）のＴＨＦ溶液を加え３０分間撹拌した。次に飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出（３×２０ｍｌ）し、有機層を飽和炭酸水素ナトリウム水溶液と飽和食塩水で洗浄後無水硫酸ナトリウムで乾燥した。濾過後、溶媒を減圧留去し、得られた粗生成物をベンゼン（１５ｍｌ）に溶かし酸性シリカゲルを２５ｍｇ加えて９時間加熱環流した。シリカゲルを濾去し、溶媒を減圧留去したのち、シリカゲルカラムクロマトグラフィで精製して無色油状の所望の生成物９３．４ｍｇ（収率６４％）を得た。
^１H~NMR (300 MHz, CDCl_３) d: 1.26 (t, J = 7.2 Hz, 3H), 1.42~1.53 (m, 1H), 1.56 (s, 3H), 1.61 (s, 3H), 2.01~2.12 (m, J = 10.0 Hz, 14.7 Hz, 2H), 2.22 (m, 2H), 2.52 (d, J = 4.4 Hz, 14.7 Hz, 1H), 2. 8 8 (m, 1H), 4.13 (q, J = 7.3 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 11.8 (q), 13.9 (q), 14.2 (q), 28.5 (t), 36.4 (t), 39.0 (t), 46.4 (d), 6 0. 0 (t), 132.2 (s), 132.4 (s), 173.4 (s)。
IR (Neat): 1737 cm^−１。
MS (EI) m/z 182 (M^＋), 95 (70%)。
HRMS (EI) calcd for C_１１H_１８O_２ 182.1307, found: 182.1283。
【００１８】
実施例２〜１１
一般式［３］において、ＸがＣＯ_２Ｅｔで、Ｒ^１，Ｒ^２が表１に記載の各組み合わせからなる２，３−ジ置換−２−シクロアルケニルアセテートを実施例１と同様にして合成した。
結果（収率）を表１にまとめて示す。
【００１９】
【表１】

【００２０】
また、各生成物の物性値を以下に示す。
◎エチル（２−ブチル−３−メチル−２−シクロペンテニル）アセテート（実施例２の化合物）
^１H~NMR (300 MHz, CDCl_３, TMS) d: 0.89 (m, 3H), 1.26 (m, J = 7.2 Hz, 7H), 1.44~1.53 (m, 1H), 1.61 (s, 3H), 1.84 (m, 1H), 2.05 (m, J = 10.4 Hz, 14.8 Hz, 2H), 2.11~2.28 (m, 3H), 2.52 (dd, J = 4. 1 Hz, 14.8 Hz, 1H), 2.99 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 13.9 (q), 14.0 (q), 14.2 (q), 22.6 (t), 25.8 (t), 28.6 (t), 30.2 (t), 36.4 (t), 38.9 (t), 43.8 (d), 60.0 (t), 132.6 (s), 136.7 (s), 173.4 (s)。
IR (Neat): 1737 cm^−１。
MS (EI) m/z 224 (M^＋), 137 (100%)。
HRMS (EI) calcd for C_１４H_２４O_２ 224.1776, found: 224.1806。
【００２１】
◎エチル（２−シクロヘキシル−３−メチル−２−シクロペンテニル）アセテート（実施例３の化合物）
^１H~NMR (300 MHz, CDCl3, TMS) d: 1.26 (m, J = 7.2 Hz, 7H), 1.51~1.74 (m, 10H), 1.89~1.96 (m, 1H), 2.09 (m, J = 11.1 Hz, 14.9 Hz, 1H), 2.23 (m, 1H), 2.32 (m, 1H), 2.57 (dd, J = 3.3Hz, 14.9 H z, 1H), 3.02 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.2 (q), 26.2 (t), 26.8 (t), 27.1 (t), 29.0 (t), 31.2 (t), 32.6 (t), 36.5 (t), 38.2 (d), 39.6 (t), 43.6 (d), 60.0 (t), 132.4 (s), 141.3 (s), 173.4 (s)。
IR (Neat): 1737 cm^−１。
MS (EI) m/z 250 (M^＋), 162 (100%)。
HRMS (EI) calcd for C_１６H_２６O_２ 250.1933, found: 250.1929。
【００２２】
◎エチル（２−メチル−３−フェニル−２−シクロペンテニル）アセテート（実施例４の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 1.28 (t, J = 7.2 Hz, 3H), 1.59~1.68 (m, 1H), 1.80 (s,3H), 2.17~2.2 9 (m, J = 9.9 Hz, 14,9 Hz, 2H), 2.61~2.72 (m, J = 4.4 Hz, 14.9 Hz, 3H), 3.08 (m, 1H), 4.16 (q, J = 7. 2 Hz, 2H), 7.19~7.36 (m, 5H)。
^１３C~NMR (75 MHz, CDCl_３) d: 13.6 (q), 14.2 (q), 28.7 (t), 35.2 (t), 38.7 (t), 47.6 (d), 60.2 (t), 126. 3 (d), 127.6 (d), 127.9 (d), 136.0 (s), 136.3 (s), 138.3 (s), 173.1 (s)。
IR (Neat): 1733, 1599, 1493, 763, 700 cm^−１。
MS (EI) m/z 244 (M+), 173 (100%)。
HRMS (EI) calcd for C_１６H_２０O_２ 244.1463, found: 244.1478。
【００２３】
◎エチル（２−ブチル−３−フェニル−２−シクロペンテニル）アセテート（実施例５の化合物）
^１H~NMR (300 MHz, CDCl_３, TMS) d: 0.85 (t, J = 7.2 Hz, 3H), 1.28 (m, J = 7.2 Hz, 7H), 1.61~1. 6 8 (m, 1H), 1.96 (m, 1H), 2.14~2.25 (m, J = 10.6 Hz, 14.9 Hz, 2H), 2.38 (m, 1H), 2.59~2.71 (m, J = 4.0 Hz, 14.9 Hz, 3H), 3.22 (m, 1H), 4.16 (q, J = 7.2 Hz, 2H), 7.19~7.35 (muti, 5H)。
^１３C~NMR (75 MHz, CDCl_３) d: 13.8 (q), 14.2 (q), 22.7 (t), 26.6 (t), 28.8 (t), 30.2 (t), 35.7 (t), 38.5 (t), 44.5 (d), 60.2 (t), 126.3 (d), 127.7 (d), 128.0 (d), 136.7 (s), 138.7 (s), 140.5 (s), 173.2 (s)。
IR (Neat): 1736, 762, 699 cm^−１。
MS (EI) m/z 286 (M^＋), 199 (100%)。
HRMS (EI) calcd for C_１９H_２６O_２ 286.1933, found: 286.1927。
【００２４】
◎エチル（２−シクロヘキシル−３−フェニル−２−シクロペンテニル）アセテート（実施例６の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 1.11~1.43 (m, J = 7.2 Hz, 9H), 1.60~1.72 (m, 5H), 2.06~2.18 (m, 1 H), 2.28 (dd, J = 11.2 Hz, 15.0 Hz, 1H), 2.46 (m, 1H), 2.57~2.68 (m, 2H), 2.75 (dd, J = 3.3 Hz, 15. 0 Hz, 1H), 3.24 (m, 1H), 4.17 (q, J = 7.2 Hz, 2H), 7.18~7.35 (muti, 5H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.3 (q), 26.1 (t), 26.5 (t), 26.7 (t), 29.8 (t), 31.6 (t). 33.2 (t), 35.9 (t), 38.7 (d), 39.4 (t), 43.4 (d), 60.2 (t), 126.3 (d), 127.8 (d), 128.0 (d), 137.0 (s), 139.1 (s), 145.1 (s), 17 3.1 (s). IR (Neat): 1732, 761, 700 cm^−１。
MS (EI) m/z 312 (M+), 224 (100%)。
HRMS (EI) calcd for C_２１H_２８O_２ 312.2089, found: 312.2117。
【００２５】
◎エチル（２，３−ジメチル−２−シクロヘキセニル）アセテート（実施例７の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 1.26 (t, J = 7.2 Hz, 3H), 1.55 (m, 4H), 1.59 (s, 3H), 1.62 (s,3H), 1. 90 (m, 2H), 2.17 (dd, J = 10.3 Hz, 14.5 Hz, 1H), 2.40 (m, 1H), 2.51 (dd, J = 3.5 Hz, 14.5 Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.2 (q), 17.3 (q), 19.2 (t), 19.5 (q), 27.9 (t), 31.8 (t), 37.0 (d), 38. 2 (t), 60.1 (t), 127.1 (s), 127.9 (s), 173.5 (s)。
IR (Neat): 1737 cm^−１。
MS (EI) m/z 196 (M^＋), 109。
HRMS (EI) calcd for C_１２H_２０O_２ 196.1463, found: 196.1468。
【００２６】
◎エチル（２−ブチル−３−メチル−２−シクロヘキセニル）アセテート（実施例８の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 0.90 (t, J = 7.2 H, 3H), 1.26 (m, J = 7.2 Hz, 7H), 1.56 (m, 4H), 1. 60 (s, 3H), 1.78 (m, 1H), 1.89 (m, 2H), 2.18 (m, J = 10.3 Hz, 14.3 Hz, 2H), 2.49 (m, J = 3.3 H z, 1 4.3 Hz, 2H), 4.14 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 13.9 (q), 14.2 (q), 18.6 (t), 19.2 (q), 22.9 (t), 27.6 (t), 30.8 (t), 31.1 (t), 31.8 (t), 34.3 (d), 38.2 (t), 60.0 (t), 127.9 (s), 132.2 (s), 173.5 (s)。
IR (Neat): 1737 cm^−１。
MS (EI) m/z 238 (M^＋), 150, 108 (100%)。
HRMS (EI) calcd for C_１５H_２６O_２ 238.133, found: 238.1905。
【００２７】
◎エチル（２−シクロヘキシル−３−メチル−２−シクロヘキセニル）アセテート（実施例９の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 1.27 (m, J = 7.2 Hz, 9H), 1.51~1.75 (m, 11H), 1.93 (m, 2H), 2.16 ~2. 34 (m, J = 11.3 Hz, 15.3 Hz, 2H), 2.48 (dd, J = 2.3 Hz, 15.3 Hz, 1H), 2.60 (m, 1H), 4.14 (q, J = 7, 2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.2 (q), 17.5 (t), 19.5 (q), 26.2 (t), 27.1 (t), 27.3 (t), 30.8 (t), 31.9 (d), 32.1 (t), 32.2 (t), 38.6 (t), 42.0 (d), 60.0 (t), 127.5 (s), 136.4 (s), 173.2 (s)。
IR (Neat): 1736 cm^−１。
MS (EI) m/z 264 (M^＋), 176 (100%)。
HRMS (EI) calcd for C_１７H_２８O_２ 264.2089, found: 264.2115。
【００２８】
◎エチル（２−ブチル−３−フェニル−２−シクロヘキセニル）アセテート（実施例１０の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 0.74 (t, J = 7.2 Hz, 3H), 1.05~1.19 (m, 2H), 1.26~1.31 (m, J = 7. 2 Hz, 5H), 1.61~1.74 (m, 5H), 1.96~2.02 (m, 1H), 2.18 (m, 2H), 2.30 (dd, J = 10.5 Hz, 15.0 Hz, 1 H), 2.59 (dd, J = 3.7 Hz, 15.0 Hz, 1H), 2.71 (m, 1H), 4.16 (q, J = 7.2 Hz, 2H), 7.07 (dd, J = 1.5 Hz, 7. 3 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1H), 7.29 (t, J = 7.3 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 13.9 (q), 14.3 (q), 19.2 (t), 22.5 (t), 27.8 (t), 30.7 (t), 30.8 (t), 32.7 (t), 32.9 (d), 38.3 (t), 60.3 (t), 125.9 (d), 128.0 (d), 128.2 (d), 134.9 (s), 135.2 (s), 144.5 (s), 173.4 (s)。
IR (Neat): 1733, 762, 702 cm^−１。
MS (EI) m/z 300 (M^＋, 100%)。
HRMS (EI) calcd for C_２０H_２８O_２ 300.2089, found: 300.2113。
【００２９】
◎エチル（２−ブチル−３−メチル−２−シクロヘプテニル）アセテート（実施例１１の化合物）
^１H~NMR (300 MHz, CDCl_３) d: 0.91 (m, 3H), 1.21~1.32 (m, J = 7.2 Hz, 9H), 1.50~1.63 (m, 4H), 1. 66 (s, 3H), 1.86 (m, 1H), 2.04 (m, 2H), 2.21 (m, 1H), 2.50 (dd, J = 6.3 Hz, 14.6 Hz, 1H), 2.54 (dd, J = 9.6 Hz, 14.6 Hz, 1H), 2.75 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.1 (q), 14.3 (q), 22.2 (t), 22.9 (t), 26.1 (t), 30.8 (t), 31.1 (t), 34.2 (t), 34.5 (t), 36.6 (t), 40.4 (d), 60.1 (t), 132.0 (s), 136.6 (s), 173.4 (s)。
IR (Neat): 1738 cm^−１。
MS (EI) m/z 252 (M^＋), 164 (100%)。
HRMS (EI) calcd for C_１６H_２８O_２ 252.2089, found: 252.2108。
【００３０】
実施例１２ エチル（２−ブチルビシクロ[4.4.0]デス−１−エン−３−イル）アセテートの合成
一般式［２］において、Ｒ^２とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になってシクロアルキル環を形成している場合の本発明の製造法の例として、シクロアルキル環がシクロヘキシル環で、ｍ＝０，ｎ＝１で、Ｒ^１がブチル基である標題化合物を実施例１と同様にして合成した（無色オイル。収率８７％。）。
^１H~NMR (300 MHz, CDCl_３) d: 0.88~0.93 (m, 3H), 1.18~1.46 (m, J = 7.2 Hz, 12H), 1.54~1.86 (m, 8H), 2.15~2.26 (m, 2H), 2.42~2.52 (m, 2H), 2.59 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.1 (q), 14.3 (q), 23.0 (t), 24.4 (t), 25.5 (t), 27.1 (t), 28.7 (t), 30.6 (t), 30.7 (t), 32.1 (t), 35.1 (d), 35.6 (t), 37.9 (t), 38.0 (d), 60.1 (t), 130.1 (s), 135.9 (s), 173.6 (s)。
IR (Neat):1732 cm^−１。
. MS (EI) m/z 278(M+), 190(100%)。
HRMS (EI) calcd for C_１８H_３０O_２ 278.2246, found: 278.2249。
【００３１】
実施例１３ エチル（３，４−ジメチル−１，２−ジヒドロナフタレン−２−イル）アセテートの合成
一般式［２］において、Ｒ^８とＲ^１０とが結合してそれぞれが結合している炭素原子と一緒になって芳香環を形成している場合の本発明の製造法の例として、芳香環がベンゼン環で、ｍ＝０，ｎ＝１でＲ^１及びＲ^２がメチル基である標題化合物を実施例１と同様にして合成した（無色オイル。収率７０％。）。
^１H~NMR (400 MHz, CDCl_３) d: 1.24 (t, J = 7.1 Hz, 3H), 1.93 (s, 3H), 2.01 (s, 3H), 2.12 (dd, J = 10.1 Hz, 15.1 Hz, 1H), 2.20 (dd, J = 4.6 Hz, 15.1 Hz, 1H), 2.60~2.68 (m, J = 15.6 Hz, 2H), 2.99 (dd, J = 6.3 Hz, 15.6 Hz, 1H), 4.07~4.15 (m, 2H), 7.08~7.12 (m, 2H), 7.18~7.24 (m, 2H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.3 (q), 14.5 (q), 19.0 (q), 32.9 (t), 34.8 (t), 36.9 (d), 60.2 (t), 122. 4 (d), 125.8 (s), 125.9 (d), 126.3 (d), 128.1 (d), 132.6 (s), 133.5 (s), 136.0 (s), 172.7 (s)。
IR (Neat): 1731, 761 cm^−１。
MS (EI) m/z 244 (M^＋), 156 (100%)。
HRMS (EI) calcd for C_１６H_２０O_２ 244.1463, found: 244.1446。
【００３２】
参考例１ エチル（３，４−ジメチルナフタレン−２−イル）アセテートの合成実施例１３で得られた化合物のトルエン溶液にジクロロジシアノ−ｐ−ベンゾキノンを加えて１時間加熱還流させたところ黄色オイル状の標題化合物が４０％の歩留で得られた。
^１H~NMR (400 MHz, CDCl_３) d: 1.25 (t, J = 7.1 Hz, 3H), 2.40 (s, 3H), 2.62 (s, 3H), 3.82 (s, 2H), 4.17 (q, J = 7.1 Hz, 2H), 7.40 (t, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.74 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H)。
^１３C~NMR (75 MHz, CDCl_３) d: 14.2 (q), 15.1 (q), 16.5 (q), 40.8 (t), 60.8 (t), 123.8 (d), 124.8 (d), 125.6 (d), 127.5 (d), 128.1 (d), 131.6 (s) 131.8 (s), 132.0 (s), 132.2 (s), 132.6 (s), 171.8 (s)。
IR (Neat): 1732, 761 cm^−１。
MS (EI) m/z 242 (M^＋), 169 (100%). HRMS (EI) calcd for C16H18O2 242.1307, found: 242.1319。
【００３３】
【発明の効果】
本発明の製造法により得られる炭素環状化合物は、医薬品や各種材料などの有用有機化合物を合成する際の原料となりうるものである。更に、これらの生成物、特に置換基が多いものについては従来法では多段階を要し、選択性も低くなるが、本発明の製造法では僅か２段階で収率も高く、精製も容易であることから工業的な規模での製造にも適しており、産業上有用な製造法であると言うことが出来る。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel process for producing polysubstituted cycloalkenes that are expected to be used in various applications as raw materials for pharmaceuticals and various materials.
[0002]
[Prior art]
Examples of the method for producing polysubstituted cycloalkenes include the synthesis method of dehydroylide diol described in J. Am. Chem. Soc. 1987, 109, 2547-2549 and Chem. Pharm. Bull. 1982, 30, 723-726, etc. is there. However, these methods require 8 steps in the former and 7 steps in the latter, and the number of steps is large and the operation is complicated.
In addition, Tetrahedron, 1980, 36, 3115-3119 synthesizes dehydroylide diol in 4 steps using limonene as a raw material, but because it is a natural product, its application to other analogs is limited and versatile. Lack.
Further, in J. Chem. Soc., Chem. Commun., 1991, 1367-1368, in the synthesis of seratopicanol, its intermediate is synthesized from limonene in 6 to 7 steps.
As described above, all the known methods for producing polysubstituted cycloalkenes have many steps, complicated operations, poor selectivity, and poor yield.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for producing a polysubstituted cycloalkene having a small number of steps, excellent selectivity, and high yield.
[0004]
[Means for Solving the Problems]
The present invention relates to a polysubstituted cycloalkene characterized in that an enolate anion and an α, β-unsaturated compound having a keto group are subjected to a tandem cycloaddition-Michael reaction, followed by a decarboxylation reaction. It relates to the manufacturing method.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
Examples of the inolate anion used in the production method of the present invention include the following general formula [1].
[Formula 4]

(In the formula, R ¹ represents an alkyl group which may have a substituent, an aryl group which may have a substituent, or an aralkyl group which may have a substituent.)
The compound shown by these is mentioned.
[0006]
As an α, β-unsaturated compound having a keto group used in the production method of the present invention, for example, the following general formula [2]
[Chemical formula 5]

(In the formula, R ² represents an alkyl group which may have a substituent, an aryl group which may have a substituent, or an aralkyl group which may have a substituent, and R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are each independently a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. Or an aralkyl group which may have a substituent, R ⁶ and R ^8, or R ⁸ and R ¹⁰ , and together with the carbon atom to which each is bonded, an aromatic ring or cyclo An alkyl ring may be formed, and R ² and R ¹⁰ may be bonded together to form a cycloalkyl ring together with the carbon atoms to which each is bonded, where X is an electron Represents an attractive functional group, and m and n each independently represent 0 or 1 .)
The compound shown by these is mentioned.
The steric structure of the alkene represented by the general formula [2] may be either cis or trans.
[0007]
Examples of the polysubstituted cycloalkenes obtained by the production method of the present invention include the following general formula [3]
[Chemical 6]

(In the formula, R ^{1 to} R ¹⁰ , X, m, and n are the same as described above.)
The compound shown by these is mentioned.
[0008]
In the general formulas [1] to [3], the alkyl group of the alkyl group which may have a substituent represented by R ^{1 to} R ¹⁰ has, for example, 1 to 20 carbon atoms, preferably 1-10, more preferably 1-6 linear, branched or cyclic alkyl groups are mentioned, more specifically, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, Examples include isobutyl group, secondary butyl group, tertiary butyl group, pentyl group, hexyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group and the like.
In addition, the aryl group of the aryl group which may have a substituent is, for example, a monocyclic, polycyclic or condensed cyclic group having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 6 to 14 carbon atoms. An aromatic hydrocarbon group is mentioned, More specifically, a phenyl group, a tolyl group, a xylyl group, a naphthyl group, a methyl naphthyl group, an anthryl group, a phenanthryl group, a biphenyl group etc. are mentioned, for example.
The aralkyl group of the aralkyl group which may have a substituent is, for example, a monocyclic, polycyclic or condensed cyclic aralkyl group having 7 to 30 carbon atoms, preferably 7 to 20 carbon atoms, more preferably 7 to 15 carbon atoms. More specifically, for example, benzyl group, phenethyl group, naphthylmethyl group, naphthylethyl group and the like can be mentioned.
In addition, as the substituent of these alkyl group, aryl group, and aralkyl group, any substituent may be used as long as it does not hinder the progress of the reaction according to the present invention. For example, alkenyl group, alkynyl group , An alkoxy group, a halogen atom, and the like.
[0009]
In the general formulas [2] and [3], examples of the electron-withdrawing functional group represented by X include a —COOR group, a —CH═NR group, a —CN group, a —SO ₂ R group (provided that R represents a hydrogen atom, an alkyl group, an aryl group, or an aralkyl group in any case, and the like, and the —COOR group is particularly preferable.
Here, examples of the alkyl group, aryl group, and aralkyl group represented by R include the same alkyl groups, aryl groups, and aralkyl groups as those represented by R ^{1 to} R ¹⁰ described above.
[0010]
The inolate anion used in the production method of the present invention can be easily synthesized, for example, according to the following reaction scheme. Tetrahedron 1998,43,2411-2422
[Chemical 7]

[0011]
That is, for example, it can be synthesized by adding tertiary butyl lithium (4 equivalents) to α, α-dibromoester and reacting at −78 degrees for 3 hours and further at 0 degrees for 30 minutes. The reaction is usually carried out in an ether solvent such as tetrahydrofuran (THF), diethyl ether, diisopropyl ether and the like.
[0012]
In the process for producing the polysubstituted cycloalkenes of the present invention, the tandem cycloaddition-Michael reaction between an inolate anion and an α, β-unsaturated compound having a keto group is usually carried out at -40 degrees to -78 degrees. And preferably at a temperature closer to -78 degrees. The reaction time is usually about 10 minutes to 1 hour, but about 30 minutes is common. The reaction is usually carried out in an ether solvent such as tetrahydrofuran (THF), diethyl ether, diisopropyl ether and the like.
The reaction for synthesizing an enolate from α, α-dibromoester and the tandem cycloaddition-Michael reaction between the generated inolate and an α, β-unsaturated compound having a keto group are usually carried out in one pot.
The decarboxylation reaction after the tandem cycloaddition-Michael reaction is usually performed by heating to reflux in the presence of an acid catalyst. As the acid, acidic silica gel, hydrochloric acid, and sulfuric acid are suitable, but acidic silica gel is generally used. The solvent is generally benzene or toluene. The reaction time is about 1 to 10 hours.
[0013]
When the production method of the present invention is shown in a reaction scheme by taking a compound having a relatively simple structure as an example, it is roughly as follows.
[Chemical 8]

[0014]
In the general formula [2], when the R ² and R ¹⁰ are bonded to each other to form a cycloalkyl ring together with the bonded carbon atoms, the production method of the present invention is reacted. The scheme is as follows.
[Chemical 9]

[0015]
Furthermore, in the general formula [2], the present invention relates to the case where R ⁶ and R ⁸ or R ⁸ and R ¹⁰ are bonded together to form an aromatic ring together with the bonded carbon atoms. The production method is shown in the reaction scheme as follows.
[Chemical Formula 10]

[0016]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, this invention is not limited at all by these Examples.
[0017]
Example 1 Synthesis of ethyl (2,3-dimethyl-2-cyclopentenyl) acetate A solution of ethyl 2,2-dibromopropionate (260 mg) in 6 ml of THF was cooled to −78 ° C. under a pentane solution of tertiary butyl lithium (2 .82 ml, 1.4 M) was added and stirred for 3 hours, followed by stirring at 0 ° C. for 30 minutes. Next, the mixture was cooled to −78 ° C., a solution of ethyl 6-oxo-2-heptenoate (136 mg) in THF was added, and the mixture was stirred for 30 minutes. Next, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate (3 × 20 ml). The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure, the resulting crude product was dissolved in benzene (15 ml), 25 mg of acidic silica gel was added, and the mixture was heated to reflux for 9 hours. The silica gel was removed by filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 93.4 mg (yield 64%) of the desired product as a colorless oil.
¹ H ~ NMR (300 MHz, CDCl ₃ ) d: 1.26 (t, J = 7.2 Hz, 3H), 1.42 ~ 1.53 (m, 1H), 1.56 (s, 3H), 1.61 (s, 3H), 2.01 ~ 2.12 (m, J = 10.0 Hz, 14.7 Hz, 2H), 2.22 (m, 2H), 2.52 (d, J = 4.4 Hz, 14.7 Hz, 1H), 2.8 8 (m, 1H), 4.13 (q , J = 7.3 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 11.8 (q), 13.9 (q), 14.2 (q), 28.5 (t), 36.4 (t), 39.0 (t), 46.4 (d), 6 0 0 (t), 132.2 (s), 132.4 (s), 173.4 (s).
IR (Neat): 1737 cm ⁻¹ .
MS (EI) m / z 182 (M ⁺ ), 95 (70%).
_{HRMS (EI) calcd for C 11} H 18 O 2 182.1307, found: 182.1283.
[0018]
Examples 2-11
In the general formula [3], a 2,3-disubstituted-2-cycloalkenyl acetate in which X is CO ₂ Et and R ¹ and R ² are each combinations shown in Table 1 was synthesized in the same manner as in Example 1. did.
The results (yield) are summarized in Table 1.
[0019]
[Table 1]

[0020]
Moreover, the physical-property value of each product is shown below.
Ethyl (2-butyl-3-methyl-2-cyclopentenyl) acetate (Compound of Example 2)
¹ H to NMR (300 MHz, CDCl ₃ , TMS) d: 0.89 (m, 3H), 1.26 (m, J = 7.2 Hz, 7H), 1.44 to 1.53 (m, 1H), 1.61 (s, 3H), 1.84 (m, 1H), 2.05 (m, J = 10.4 Hz, 14.8 Hz, 2H), 2.11 to 2.28 (m, 3H), 2.52 (dd, J = 4.1 Hz, 14.8 Hz, 1H), 2.99 ( m, 1H), 4.13 (q, J = 7.2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 13.9 (q), 14.0 (q), 14.2 (q), 22.6 (t), 25.8 (t), 28.6 (t), 30.2 (t), 36.4 ( t), 38.9 (t), 43.8 (d), 60.0 (t), 132.6 (s), 136.7 (s), 173.4 (s).
IR (Neat): 1737 cm ⁻¹ .
MS (EI) m / z 224 (M ⁺ ), 137 (100%).
_{HRMS (EI) calcd for C 14} H 24 O 2 224.1776, found: 224.1806.
[0021]
エ チ ル Ethyl (2-cyclohexyl-3-methyl-2-cyclopentenyl) acetate (compound of Example 3)
¹ H to NMR (300 MHz, CDCl3, TMS) d: 1.26 (m, J = 7.2 Hz, 7H), 1.51 to 1.74 (m, 10H), 1.89 to 1.96 (m, 1H), 2.09 (m, J = 11.1 Hz, 14.9 Hz, 1H), 2.23 (m, 1H), 2.32 (m, 1H), 2.57 (dd, J = 3.3Hz, 14.9 Hz, 1H), 3.02 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.2 (q), 26.2 (t), 26.8 (t), 27.1 (t), 29.0 (t), 31.2 (t), 32.6 (t), 36.5 ( t), 38.2 (d), 39.6 (t), 43.6 (d), 60.0 (t), 132.4 (s), 141.3 (s), 173.4 (s).
IR (Neat): 1737 cm ⁻¹ .
MS (EI) m / z 250 (M ⁺ ), 162 (100%).
_{HRMS (EI) calcd for C 16} H 26 O 2 250.1933, found: 250.1929.
[0022]
Ethyl (2-methyl-3-phenyl-2-cyclopentenyl) acetate (Compound of Example 4)
¹ H to NMR (300 MHz, CDCl ₃ ) d: 1.28 (t, J = 7.2 Hz, 3H), 1.59 to 1.68 (m, 1H), 1.80 (s, 3H), 2.17 to 2.29 (m, J = 9.9 Hz, 14,9 Hz, 2H), 2.61 to 2.72 (m, J = 4.4 Hz, 14.9 Hz, 3H), 3.08 (m, 1H), 4.16 (q, J = 7.2 Hz, 2H), 7.19 ~ 7.36 (m, 5H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 13.6 (q), 14.2 (q), 28.7 (t), 35.2 (t), 38.7 (t), 47.6 (d), 60.2 (t), 126. 3 (d), 127.6 (d), 127.9 (d), 136.0 (s), 136.3 (s), 138.3 (s), 173.1 (s).
IR (Neat): 1733, 1599, 1493, 763, 700 cm ⁻¹ .
MS (EI) m / z 244 (M +), 173 (100%).
HRMS (EI) calcd for C ₁₆ H ₂₀ O ₂ 244.1463, found: 244.1478.
[0023]
Ethyl (2-butyl-3-phenyl-2-cyclopentenyl) acetate (Compound of Example 5)
¹ H to NMR (300 MHz, CDCl ₃ , TMS) d: 0.85 (t, J = 7.2 Hz, 3H), 1.28 (m, J = 7.2 Hz, 7H), 1.61 to 1.6 8 (m, 1H) , 1.96 (m, 1H), 2.14 to 2.25 (m, J = 10.6 Hz, 14.9 Hz, 2H), 2.38 (m, 1H), 2.59 to 2.71 (m, J = 4.0 Hz, 14.9 Hz, 3H), 3.22 (m, 1H), 4.16 (q, J = 7.2 Hz, 2H), 7.19-7.35 (muti, 5H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 13.8 (q), 14.2 (q), 22.7 (t), 26.6 (t), 28.8 (t), 30.2 (t), 35.7 (t), 38.5 ( t), 44.5 (d), 60.2 (t), 126.3 (d), 127.7 (d), 128.0 (d), 136.7 (s), 138.7 (s), 140.5 (s), 173.2 (s).
IR (Neat): 1736, 762, 699 cm ⁻¹ .
MS (EI) m / z 286 (M ⁺ ), 199 (100%).
HRMS (EI) calcd for C ₁₉ H ₂₆ O ₂ 286.1933, found: 286.1927.
[0024]
エ チ ル Ethyl (2-cyclohexyl-3-phenyl-2-cyclopentenyl) acetate (compound of Example 6)
¹ H to NMR (300 MHz, CDCl ₃ ) d: 1.11 to 1.43 (m, J = 7.2 Hz, 9H), 1.60 to 1.72 (m, 5H), 2.06 to 2.18 (m, 1 H), 2.28 (dd, J = 11.2 Hz, 15.0 Hz, 1H), 2.46 (m, 1H), 2.57 to 2.68 (m, 2H), 2.75 (dd, J = 3.3 Hz, 15.0 Hz, 1H), 3.24 (m, 1H) 4.17 (q, J = 7.2 Hz, 2H), 7.18-7.35 (muti, 5H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.3 (q), 26.1 (t), 26.5 (t), 26.7 (t), 29.8 (t), 31.6 (t). 33.2 (t), 35.9 ( t), 38.7 (d), 39.4 (t), 43.4 (d), 60.2 (t), 126.3 (d), 127.8 (d), 128.0 (d), 137.0 (s), 139.1 (s), 145.1 ( s), 17 3.1 (s). IR (Neat): 1732, 761, 700 cm ⁻¹ .
MS (EI) m / z 312 (M +), 224 (100%).
HRMS (EI) calcd for C ₂₁ H ₂₈ O ₂ 312.2089, found: 312.2117.
[0025]
Ethyl (2,3-dimethyl-2-cyclohexenyl) acetate (Compound of Example 7)
¹ H ~ NMR (300 MHz, CDCl ₃ ) d: 1.26 (t, J = 7.2 Hz, 3H), 1.55 (m, 4H), 1.59 (s, 3H), 1.62 (s, 3H), 1.90 ( m, 2H), 2.17 (dd, J = 10.3 Hz, 14.5 Hz, 1H), 2.40 (m, 1H), 2.51 (dd, J = 3.5 Hz, 14.5 Hz, 1H), 4.14 (q, J = 7.2 Hz , 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.2 (q), 17.3 (q), 19.2 (t), 19.5 (q), 27.9 (t), 31.8 (t), 37.0 (d), 38. 2 (t), 60.1 (t), 127.1 (s), 127.9 (s), 173.5 (s).
IR (Neat): 1737 cm ⁻¹ .
MS (EI) m / z 196 (M ⁺ ), 109.
_{HRMS (EI) calcd for C 12} H 20 O 2 196.1463, found: 196.1468.
[0026]
Ethyl (2-butyl-3-methyl-2-cyclohexenyl) acetate (Compound of Example 8)
¹ H-NMR (300 MHz, CDCl ₃ ) d: 0.90 (t, J = 7.2 H, 3H), 1.26 (m, J = 7.2 Hz, 7H), 1.56 (m, 4H), 1.60 (s, 3H), 1.78 (m, 1H), 1.89 (m, 2H), 2.18 (m, J = 10.3 Hz, 14.3 Hz, 2H), 2.49 (m, J = 3.3 Hz, 14.3 Hz, 2H), 4.14 (q, J = 7.2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 13.9 (q), 14.2 (q), 18.6 (t), 19.2 (q), 22.9 (t), 27.6 (t), 30.8 (t), 31.1 ( t), 31.8 (t), 34.3 (d), 38.2 (t), 60.0 (t), 127.9 (s), 132.2 (s), 173.5 (s).
IR (Neat): 1737 cm ⁻¹ .
MS (EI) m / z 238 (M ⁺ ), 150, 108 (100%).
_{HRMS (EI) calcd for C 15} H 26 O 2 238.133, found: 238.1905.
[0027]
Ethyl (2-cyclohexyl-3-methyl-2-cyclohexenyl) acetate (Compound of Example 9)
¹ H to NMR (300 MHz, CDCl ₃ ) d: 1.27 (m, J = 7.2 Hz, 9H), 1.51 to 1.75 (m, 11H), 1.93 (m, 2H), 2.16 to 2.34 (m, J = 11.3 Hz, 15.3 Hz, 2H), 2.48 (dd, J = 2.3 Hz, 15.3 Hz, 1H), 2.60 (m, 1H), 4.14 (q, J = 7, 2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.2 (q), 17.5 (t), 19.5 (q), 26.2 (t), 27.1 (t), 27.3 (t), 30.8 (t), 31.9 ( d), 32.1 (t), 32.2 (t), 38.6 (t), 42.0 (d), 60.0 (t), 127.5 (s), 136.4 (s), 173.2 (s).
IR (Neat): 1736 cm ⁻¹ .
MS (EI) m / z 264 (M ⁺ ), 176 (100%).
_{HRMS (EI) calcd for C 17} H 28 O 2 264.2089, found: 264.2115.
[0028]
Ethyl (2-butyl-3-phenyl-2-cyclohexenyl) acetate (Compound of Example 10)
¹ H to NMR (300 MHz, CDCl ₃ ) d: 0.74 (t, J = 7.2 Hz, 3H), 1.05 to 1.19 (m, 2H), 1.26 to 1.31 (m, J = 7.2 Hz, 5H), 1.61 ~ 1.74 (m, 5H), 1.96 ~ 2.02 (m, 1H), 2.18 (m, 2H), 2.30 (dd, J = 10.5 Hz, 15.0 Hz, 1 H), 2.59 (dd, J = 3.7 Hz, 15.0 Hz, 1H), 2.71 (m, 1H), 4.16 (q, J = 7.2 Hz, 2H), 7.07 (dd, J = 1.5 Hz, 7.3 Hz, 2H), 7.20 (t, J = 7.3 Hz , 1H), 7.29 (t, J = 7.3 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 13.9 (q), 14.3 (q), 19.2 (t), 22.5 (t), 27.8 (t), 30.7 (t), 30.8 (t), 32.7 ( t), 32.9 (d), 38.3 (t), 60.3 (t), 125.9 (d), 128.0 (d), 128.2 (d), 134.9 (s), 135.2 (s), 144.5 (s), 173.4 ( s).
IR (Neat): 1733, 762, 702 cm ⁻¹ .
MS (EI) m / z 300 (M ⁺ , 100%).
_{HRMS (EI) calcd for C 20} H 28 O 2 300.2089, found: 300.2113.
[0029]
Ethyl (2-butyl-3-methyl-2-cycloheptenyl) acetate (Compound of Example 11)
¹ H ~ NMR (300 MHz, CDCl ₃ ) d: 0.91 (m, 3H), 1.21 ~ 1.32 (m, J = 7.2 Hz, 9H), 1.50 ~ 1.63 (m, 4H), 1. 66 (s, 3H ), 1.86 (m, 1H), 2.04 (m, 2H), 2.21 (m, 1H), 2.50 (dd, J = 6.3 Hz, 14.6 Hz, 1H), 2.54 (dd, J = 9.6 Hz, 14.6 Hz, 1H), 2.75 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.1 (q), 14.3 (q), 22.2 (t), 22.9 (t), 26.1 (t), 30.8 (t), 31.1 (t), 34.2 ( t), 34.5 (t), 36.6 (t), 40.4 (d), 60.1 (t), 132.0 (s), 136.6 (s), 173.4 (s).
IR (Neat): 1738 cm ⁻¹ .
MS (EI) m / z 252 (M ⁺ ), 164 (100%).
HRMS (EI) calcd for C ₁₆ H ₂₈ O ₂ 252.2089, found: 252.2108.
[0030]
Example 12 Synthesis of ethyl (2-butylbicyclo [4.4.0] des-1-en-3-yl) acetate In general formula [2], R ² and R ¹⁰ are bonded to each other. As an example of the production method of the present invention when a cycloalkyl ring is formed together with a carbon atom, the cycloalkyl ring is a cyclohexyl ring, m = 0, n = 1, and R ¹ is a butyl group. The title compound was synthesized as in Example 1 (colorless oil, yield 87%).
¹ H to NMR (300 MHz, CDCl ₃ ) d: 0.88 to 0.93 (m, 3H), 1.18 to 1.46 (m, J = 7.2 Hz, 12H), 1.54 to 1.86 (m, 8H), 2.15 to 2.26 (m , 2H), 2.42 to 2.52 (m, 2H), 2.59 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.1 (q), 14.3 (q), 23.0 (t), 24.4 (t), 25.5 (t), 27.1 (t), 28.7 (t), 30.6 ( t), 30.7 (t), 32.1 (t), 35.1 (d), 35.6 (t), 37.9 (t), 38.0 (d), 60.1 (t), 130.1 (s), 135.9 (s), 173.6 ( s).
IR (Neat): 1732 cm ⁻¹ .
MS (EI) m / z 278 (M +), 190 (100%).
_{HRMS (EI) calcd for C 18} H 30 O 2 278.2246, found: 278.2249.
[0031]
Example 13 Synthesis of ethyl (3,4-dimethyl-1,2-dihydronaphthalen-2-yl) acetate In general formula [2], carbon atoms to which R ⁸ and R ¹⁰ are bonded to each other As an example of the production method of the present invention in the case of forming an aromatic ring together with a title compound, the aromatic ring is a benzene ring, m = 0, n = 1, and R ¹ and R ² are methyl groups Was synthesized in the same manner as in Example 1 (colorless oil, yield 70%).
¹ H ~ NMR (400 MHz, CDCl ₃ ) d: 1.24 (t, J = 7.1 Hz, 3H), 1.93 (s, 3H), 2.01 (s, 3H), 2.12 (dd, J = 10.1 Hz, 15.1 Hz , 1H), 2.20 (dd, J = 4.6 Hz, 15.1 Hz, 1H), 2.60 to 2.68 (m, J = 15.6 Hz, 2H), 2.99 (dd, J = 6.3 Hz, 15.6 Hz, 1H), 4.07 to 4.15 (m, 2H), 7.08 to 7.12 (m, 2H), 7.18 to 7.24 (m, 2H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.3 (q), 14.5 (q), 19.0 (q), 32.9 (t), 34.8 (t), 36.9 (d), 60.2 (t), 122. 4 (d), 125.8 (s), 125.9 (d), 126.3 (d), 128.1 (d), 132.6 (s), 133.5 (s), 136.0 (s), 172.7 (s).
IR (Neat): 1731, 761 cm ⁻¹ .
MS (EI) m / z 244 (M ⁺ ), 156 (100%).
HRMS (EI) calcd for C ₁₆ H ₂₀ O ₂ 244.1463, found: 244.1446.
[0032]
Reference Example 1 Synthesis of ethyl (3,4-dimethylnaphthalen-2-yl) acetate Dichlorodicyano-p-benzoquinone was added to a toluene solution of the compound obtained in Example 13 and heated under reflux for 1 hour. Of the title compound was obtained with a yield of 40%.
¹ H to NMR (400 MHz, CDCl ₃ ) d: 1.25 (t, J = 7.1 Hz, 3H), 2.40 (s, 3H), 2.62 (s, 3H), 3.82 (s, 2H), 4.17 (q, J = 7.1 Hz, 2H), 7.40 (t, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.74 (d, J = 7.8 Hz, 1H) , 8.00 (d, J = 7.8 Hz, 1H).
¹³ C-NMR (75 MHz, CDCl ₃ ) d: 14.2 (q), 15.1 (q), 16.5 (q), 40.8 (t), 60.8 (t), 123.8 (d), 124.8 (d), 125.6 ( d), 127.5 (d), 128.1 (d), 131.6 (s) 131.8 (s), 132.0 (s), 132.2 (s), 132.6 (s), 171.8 (s).
IR (Neat): 1732, 761 cm ⁻¹ .
MS (EI) m / z 242 (M ⁺ ), 169 (100%). HRMS (EI) calcd for C16H18O2 242.1307, found: 242.1319.
[0033]
【The invention's effect】
The carbocyclic compound obtained by the production method of the present invention can be a raw material for synthesizing useful organic compounds such as pharmaceuticals and various materials. Furthermore, these products, particularly those having a large number of substituents, require many steps in the conventional method and have low selectivity. However, in the production method of the present invention, the yield is high in two steps and purification is easy. Therefore, it is suitable for manufacturing on an industrial scale and can be said to be an industrially useful manufacturing method.

Claims (9)

A process for producing a polysubstituted cycloalkene, which comprises subjecting an inolate anion and an α, β-unsaturated compound having a keto group to a tandem cycloaddition-Michael reaction followed by a decarboxylation reaction. The production method according to claim 1, wherein the decarboxylation reaction is carried out by heating under an acid catalyst. The inolate anion is represented by the following general formula [1]

(In the formula, R ¹ represents an alkyl group which may have a substituent, an aryl group which may have a substituent, or an aralkyl group which may have a substituent.)
The manufacturing method of Claim 1 or 2 which is an anion shown by these. The α, β-unsaturated compound having a keto group is represented by the following general formula [2]

(In the formula, R ² represents an alkyl group which may have a substituent, an aryl group which may have a substituent, or an aralkyl group which may have a substituent, and R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are each independently a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. Or an aralkyl group which may have a substituent, R ⁶ and R ^8, or R ⁸ and R ¹⁰ , and together with the carbon atom to which each is bonded, an aromatic ring or cyclo An alkyl ring may be formed, and R ² and R ¹⁰ may be bonded together to form a cycloalkyl ring together with the carbon atoms to which each is bonded, where X is an electron Represents an attractive functional group, and m and n each independently represent 0 or 1 .)
The production method according to any one of claims 1 to 3, wherein the compound is represented by the formula: The electron-withdrawing functional group is a —COOR group, —CH═NR group, —CN group or —SO ₂ R group (where R is a hydrogen atom, an alkyl group, an aryl group or an aralkyl group in any case). The production method according to claim 4, wherein The production method according to claim 4, wherein the electron-withdrawing functional group is a —COOR group (wherein R is as defined above). The polysubstituted cycloalkenes are represented by the following general formula [3]

(In the formula, R ^{1 to} R ¹⁰ , X, m, and n are the same as described above.)
The production method according to any one of claims 1 to 4, which is a compound represented by the formula: X is, -COOR group, -CH = NR group, -CN group or -SO ₂ R group (wherein, R represents the same. As above) Process according to Claim 7 is. The production method according to claim 7, wherein X is a -COOR group (wherein R is the same as defined above).