Aromatic Heterocycles as Productive Dienophiles in the Inverse Electron-Demand Diels–Alder Reactions of 1,3,5-Triazines

区域选择性 化学 反应性(心理学) 三嗪 组合化学 有机合成 有机化学 催化作用 医学 替代医学 病理
作者
Guoxing Xu,Xu Bai,Qun Dang
出处
期刊:Accounts of Chemical Research [American Chemical Society]
卷期号:53 (4): 773-781 被引量:26
标识
DOI:10.1021/acs.accounts.9b00604
摘要

ConspectusHeterocycles are often found as the structural nucleus in natural products and biological active compounds. Consequently, research toward the discovery and development of novel and efficient synthetic methodologies is of constant interest to organic chemists. Diels–Alder reactions are powerful at forming multiple bonds simultaneously, often with stereoselectivity, and thus are one of the most widely used synthetic methodologies in organic syntheses. Inverse electron-demand Diels–Alder (IEDDA) reactions, a subclass of Diels–Alder reactions, have been developed for the efficient synthesis of various heterocycles, with 1,3,5-triazines used as azadienes. The initial 1,3,5-triazine IEDDA reactions mostly included nonaromatic, electron-rich species such as vinyl ethers, enamines, ynamines, and amidines as dienophiles, producing in high yields pyrimidine derivatives with excellent regioselectivity. We hypothesized that some electron-rich aromatic heterocycles could be studied as potential dienophiles for 1,3,5-triazine IEDDA reactions; 5-aminopyrazoles proved to be productive dienophiles leading to high yields of pyrazolopyrimidines. Subsequently, many studies were reported to investigate the mechanism and scope of this new type of IEDDA reaction. Mechanistically, this new type of IEDDA reaction is quite interesting since it entails two aromatic compounds proceeding through a perceived high energy nonaromatic transition state, leading to a new aromatic compound, a counterintuitive process. Both theoretical and experimental studies provide key insights to this reaction mechanism, with learnings from these studies possibly stimulating unconventional thinking in other areas. Theoretical calculations of these cascade reactions of amino-substituted heterocycles with 1,3,5-triazines indicate that the reactions occur in a stepwise fashion via a highly polar zwitterionic intermediate; elimination of ammonia from IEDDA adducts and subsequent retro Diels–Alder reaction drive the reaction toward the fully aromatized IEDDA products. This amino substituent is critical in determining the regioselectivity and driving the cascade reactions to completion. With regard to reaction scope, many amino-heterocycles such as pyrroles, imidazoles, furans, thiophenes, and indoles all proved to be productive dienophiles for this new IEDDA reaction, leading to various fused-pyrimidines in a single step with moderate to high yields and high regioselectivity. Application of this new IEDDA reaction with 1,3,5-triazines was reported to lead to interesting heterocyclic compounds such as nucleoside natural product nebularine and analogues, as well as fluorine-containing fused pyrimidines with potential for biological activities.Herein, the scope of various aromatic heterocycles as dienophiles in the 1,3,5-triazine IEDDA reaction is reviewed. Moreover, both experimental and theoretical studies of the mechanisms for this interesting cascade IEDDA reaction are discussed. Finally, applications of this new type (aromatic heterocycles as dienophiles with 1,3,5-triazines as azadienes) of IEDDA reaction are also covered.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
apckkk完成签到 ,获得积分10
1秒前
深情安青应助550190946采纳,获得10
2秒前
3秒前
4秒前
jbq完成签到 ,获得积分20
4秒前
YM完成签到,获得积分10
6秒前
生动柔发布了新的文献求助10
6秒前
大旭完成签到 ,获得积分10
7秒前
Fn完成签到 ,获得积分10
9秒前
zero完成签到,获得积分10
11秒前
瘦瘦谷兰完成签到,获得积分10
11秒前
zcz完成签到 ,获得积分10
12秒前
白嘉乐完成签到,获得积分10
13秒前
考研小白完成签到,获得积分10
13秒前
高妍纯完成签到 ,获得积分10
15秒前
17秒前
风中的丝袜完成签到,获得积分10
17秒前
赵赵完成签到,获得积分10
20秒前
20秒前
shiizii应助科研通管家采纳,获得10
21秒前
xuzj应助科研通管家采纳,获得10
21秒前
Mars应助科研通管家采纳,获得30
21秒前
Hello应助科研通管家采纳,获得10
21秒前
叶梓轩完成签到 ,获得积分10
21秒前
上官若男应助科研通管家采纳,获得10
21秒前
21秒前
21秒前
机智的锦程完成签到 ,获得积分10
22秒前
时尚俊驰发布了新的文献求助10
24秒前
华仔完成签到,获得积分10
24秒前
甜甜友容完成签到,获得积分10
28秒前
程哲瀚完成签到,获得积分10
28秒前
28秒前
副本完成签到 ,获得积分10
28秒前
淡然画笔完成签到,获得积分10
29秒前
生动柔完成签到,获得积分20
29秒前
雨天完成签到,获得积分10
30秒前
喜悦寒凝完成签到,获得积分10
30秒前
LLSSLL完成签到,获得积分10
31秒前
lenetivy发布了新的文献求助20
31秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038201
求助须知:如何正确求助?哪些是违规求助? 3575940
关于积分的说明 11373987
捐赠科研通 3305747
什么是DOI,文献DOI怎么找? 1819274
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022