Construction of Ring-Flourinated Heterocycles via Intramolecular Substitutions for Vinylic Flourines

通过乙烯基氟的分子内取代构建环状氟化杂环

基本信息

批准号：
09640641
负责人：
ICHIKAWA Junji
金额：
$ 2.43万
依托单位：
KYUSHU INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Selectively fluorinated heterocycles are widely used as important components in the agrochemical, pharmaceutical, and dyestuffs industries. Only a limited number of methods, however, have been reported for the synthesis of ring-fluorinated heterocyclic compounds. We have developed new synthetic reactions to construct these ring systems starting from functionalized gem-difluoroolefins. which are subject to replacement of the fluorines by nucleophiles via addition-elimination process. The employed substrates of difluoroolefins are easily prepared from 2,2,2-trifluoroethyl p-toluenesulfonate by the general synthetic method that we have recently developed.The replacement of fluorine is successfully effected in gem-difluoroolefins with a nucleophilic N-, 0-, S-, or C-functional group. gem-Difluorostyrenes, bearing HOCH_2, AcSCH_2, or TsNHCH_2 group at the ortho position, readily undergo intramolecular substitution, leading to six-membered rings such as 3-fluoroisochromene, -thioisochipmene, and -isoquinoline derivatives, respectively. The following in-situ generated nitrogen or carbon nucleophiles in gern-difluorostyrenes also effect this type of intramolecular substitution. When o-cyano, isocyano, formyl, and amino groups are transformed to the corresponding nucleophiles, the desired cyclizations readily proceed to afford 3-fluorinated isoquinolines, quinolines, isoquinoline N-oxides, and cinnolines in high yields.Furthermore, this methodology can be applied to the formation of five-membered rings even via 5-endo-trigonal cycization, which is disfavored in Baldwin's rules. The ring closure smoothly proceeds to give 2-fluoroindoles, -benzofurans, and -benzothiophenes, probably due to (i) the highly polarized double bond of difluoroolefins and (ii) the elimination of a fluoride ion.Substrates without a fused benzene ring are also emploed in this methodology.

在农业化学，药物和染料工业中，有选择的氟化杂环被广泛用作重要组成部分。然而，仅报告了有限的方法来合成环氟化合物化合物。我们已经开发了新的合成反应，以构建从功能化的宝石 - 二氟此化开始的这些环系统。通过添加 - 灭绝过程，由亲核试剂替代氟。通过我们最近开发的一般合成方法，可以轻松地从2,2,2-三氟乙基p-二甲磺酸盐中制备使用的Difluoroolefins的使用的底物。荧光的替换在Gem-Diffluorooloroolefins中成功实现，并用核网n-，0-，0-，0-，0-，s-，s-，或c-Funsils cunsement。在正位位置的宝石 - 二氟杆菌，轴承HOCH_2，ACSCH_2或TSNHCH_2组，很容易接受分子内替代，从而形成了六元的环，例如3-氟二柔蛋白的戒指，分别是-thiioochipmene和-isoquinoline derivations。以下原位在Gern-二氟抑菌素中产生的氮或碳亲核试剂也会影响这种类型的分子内取代。当O-Cyano，Isocyano，emyl和氨基群转化为相应的亲核器时，所需的循环易于提供3氟化的等喹啉，奎诺氨酸，等喹啉，N-氧化物，以及高收益的cinnoLines，该方法论是5个方法，甚至是五个方法，甚至是五型符合性的符合性的符号，即五型。循环，这在鲍德温的规则中不受欢迎。环闭合可以顺利进行，从而产生2-氟乙呋喃和-Benzothiophenes，这可能是由于（i）（i）（i）Difluoroolefins的高度极化的双键，以及（ii）消除氟化物离子。在这种方法中，没有融合苯苯环没有融合的苯苯环。