EXTRACYCLIC STEREOCONTROLLED ALKYLATION OF (1R,5S)-4-ETHYL-6,6-DIMETHYL-3-(PHENYLSULFONYL)BICYCLO[3.1.1]HEPT-3-EN-2-ONE - A HIGHLY STEREOCONTROLLED SYNTHESIS OF (-)-KANSHONE-A
EXTRACYCLIC STEREOCONTROLLED ALKYLATION OF (1R,5S)-4-ETHYL-6,6-DIMETHYL-3-(PHENYLSULFONYL)BICYCLO[3.1.1]HEPT-3-EN-2-ONE - A HIGHLY STEREOCONTROLLED SYNTHESIS OF (-)-KANSHONE-A
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DOI：
10.1021/jo00071a025
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发表时间：
1993-09-10
影响因子：
3.6
通讯作者：
AWEN, BZ
中科院分区：
文献类型：
--
作者：
KATO, M;WATANABE, M;AWEN, BZ
以(+)-nopinone(1)为原料，通过(1R,5R)-6,6-二甲基-3-（苯基磺酰基）双环[3.1]经6步合成(1R,5S)-4-乙基-6,6-二甲基-3-（苯基磺酰基）双环[3.1.1]，总收率为70%。l] hept-3-en-2-one(2)。在K2CO3存在下，7在MeCN中与烷基溴16 （a，烯丙基，b， 3-甲基-2-丁基，c，丙炔基，d，苄基溴）以区域和外环立体控制的方式进行烷基化反应，主要产物为具有新R构型手性中心的17a-d和具有S构型手性中心的18a-d，其比例为17a-18a， 10:1, 17b-18b, 7:1；17 c-18c,十三1;17d-18d, 18:1，与α -烷基化产物19a-d和0-烷基化产物20a，b与16a，b反应。此外，7与溴乙酸甲酯（16e）反应得到17e为唯一产物。在组合试剂K2CO3-Cs2CO3（9:1）存在的情况下，在MeCN中检测到相当高的非对位选择，即7与16a，b反应产生17a和18a的混合物，17b和18b分别以20:1和12:1的比例。反应产物经硅胶层析分离，主要的非对映体17a、c-e本身具有高结晶性，通过重结晶可获得纯结晶。简要讨论了非对映选择的机理以及外环立体控制烷基化的范围和局限性。在应用17作为合成中间体进行不对称合成时，以(1R,5S)-6,6-二甲基-4-[(1R)-1-甲基-3-丁烯基]-3-（苯基磺酰基）双环[3.l.]摘要以(1R,4R,5R)-4,6,6-三甲基-4-[(1R)- 1-甲基-3-丁烯基]双环[3.1.1]庚烷-2-酮（30）及其环丁烷开环产物(4S,4aR,5R)-1-乙酰氧基-4-异丙烯-4a，5-二甲基-3,4,4a,5,6,7-六氢萘（34）为原料，经12步高立体选择性合成了一种纳多辛烷倍半萜烯(8)。
(1R,5S)-4-Ethyl-6,6-dimethyl-3-(phenylsulfonyl)bicyclo[3.1.1]hept-3-en-2-one (7) was prepared from (+)-nopinone (1) in six steps and 70% overall yield via (1R,5R)-6,6-dimethyl-3-(phenylthio)bicyclo-[3.1.l]hept-3-en-2-one (2). Alkylation reactions of 7 with alkyl bromides 16 (a, allyl; b, 3-methyl-2-butenyl; c, propargyl; d, benzyl bromide) in the presence of K2CO3 in MeCN proceeded in regio- and extracyclic stereocontrolled fashion to give, as the major product, mixtures of gamma-alkylated products 17a-d possessing a new chiral center of R configuration adjacent to a ring and 18a-d possessing that of S configuration, whose ratios are 17a-18a, 10:1, 17b-18b, 7:1; 17c-18c, 13:1; and 17d-18d, 18:1, along with alpha-alkylated products 19a-d and 0-alkylated products 20a,b on reactions with 16a,b. In addition, reaction of 7 with methyl bromoacetate (16e) provided 17e as the sole product. In the presence of a combined reagent, K2CO3-Cs2CO3 (9:1), in MeCN, considerably high diastereoselection was detected, i.e., reactions of 7 with 16a,b produced mixtures of 17a and 18a, and 17b and 18b, in 20:1 and 12:1 ratios, respectively. Reaction products were separated by chromatography on silica gel, while the major diastereomers 17a,c-e, highly crystalline themselves, were readily obtained as pure crystals by recrystallization. Mechanism of diastereoselection and the scope and limitations of the extracyclic stereocontrolled alkylation are briefly discussed. In the application of 17 as the synthetic intermediate for the asymmetric synthesis, starting with (1R,5S)-6,6-dimethyl-4-[(1R)-1-methyl-3-butenyl]-3-(phenylsulfonyl)bicyclo[3.l.l]hept-3-en-2-one (17a), (-)-kanshone A (8), a nardosinane sesquiterpene, was synthesized in a highly stereoselective fashion in 12 steps via (1R,4R,5R)-4,6,6-trimethyl-4-[(1R)-l-methyl-3-butenyl]bicyclo[3.1.1]heptan-2-one (30) and its cyclobutane-ring opening product, (4S,4aR,5R)-1-acetoxy-4-isopropenyl-4a,5-dimethyl-3,4,4a,5,6,7-hexahydronaphthalene (34).