Domino process reactions in organic synthesis 导师：高建荣 金红卫 有机化学 吴志 2008.4
What is Domino? 多米诺骨牌和多米诺骨牌效应 多米诺骨牌（domino）是一种用木制、骨制或塑料制成的长方形骨牌。玩时将骨牌按一定间距排列成行，轻轻碰倒第一枚骨牌，其余的骨牌就会产生连锁反应，依次倒下。 这种效应的物理道理是：骨牌竖着时，重心较高，倒下时重心下降，倒下过程中，将其重力势能转化为动能，它倒在第二张牌上，这个动能就转移到第二张牌上，第二张牌将第一张牌转移来的动能和自己倒下过程中由本身具有的重力势能转化来的动能之和，再传到第三张牌上。。。。。。所以每张牌倒下的时候，具有的动能都比前一块牌大，因此它们的速度一个比一个快，也就是说，它们依次推倒的能量一个比一个大。
What is domino reaction? In an ideal procedure, the entire transformation should be run without the addition of any further reagents or catalysts, and without changing the reaction conditions. We have defined this type of transformation as a “domino reaction” or “domino process”. Such a process would be the transformation of two or more bond-forming reactions under identical reaction conditions, in which the latter transformations take place at the functionalities obtained in the former bond forming reactions.
A visible example of this type is the highly stereoselective formation of lanosterol(羊毛甾醇) (0-6) from (S)-2,3-oxidosqualene(2,3-环氧三十碳六烯) (0-5) in Nature, which seems not to follow a concerted mechanism (Scheme 0.2) . Like domino stones, where one stone tips over the next, which tips the next, and the next . . . such that they all fall down in turn. K. U. Wendt, G. E. Schulz, E. J. Corey, D. R. Liu, Angew. Chem. Int. Ed. 2000, 39,2812−2833
Why we search for domino process reactions? • The use of domino reactions has these main advantages. • First ,to the chemical industry, as the costs not only for waste management but also for energy supplies and materials are reduced. • Second , the beneficial effect on the environment, as domino reactions help to save natural resources. • Third , time-resolved transformations It is, therefore, not surprising that this new concept has been adopted very rapidly by the scientific community.
Classification of domino process reactions • 1 Cationic Domino Reactions • 2 Anionic Domino Reactions • 3 Radical Domino Reactions • 4 Pericyclic Domino Reactions
Cationic Domino Reactions The termination of cationic cyclizations by the use of pinacol rearrangements has shown to be a powerful tool for developing stereoselective ring-forming domino reactions. During the past few years, the Overman group has invested much effort in the design of fascinating domino Prins cyclization/pinacol rearrangement sequences for the synthesis of carbocyclic and heterocyclic compounds, especially with regard to target-directed assembly of natural products
Lewis acid-induced ring-expanding cyclopentane（环戊烷） annulation（环壮物） of the 1-alkenylcycloalkanyl silyl ether 1-8. The oxenium ion 1-9 produced performed a 6-endo Prins cyclization with the tethered alkene moiety, giving cyclic carbocation 1-10. the latter directly underwent a pinacol nrearrangement resulting in the formation of cycloalkanone 1-11. A one-carbon expansion of the substrate 1-8.
Triflic(三氟甲磺酸) anhydride(酐) and DTBMP, pyrrolidine amide 1-20 was converted into the keteniminium(烯酮亚胺) ion 1-22, Cyclization through a chairlike transition state provided carbocation 1-23, a pinacol rearrangement to give enamine 1-24.
Anionic Domino Reactions Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet−Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carbanion, an enolate, or an alkoxide) or a “pseudo” anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new “real” or “pseudo-anionic” functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X− group. Anionic/Anionic Processes---Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions0000000 is initiated by a Michael addition. Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN type sequences have been found in the literature.
Schneider and coworkers produced functionalized enantiopure cyclohexanes of type 2-94, starting from 2-93 and a cuprate with excellent selectivity of >95:5 (Scheme 2.21) .The stereochemical outcome can be explained taking the TS 2-95 and TS 2-96 into account.
Radical Domino Reactions Usually, free-radical domino processes are characterized by a sequence of intramolecular steps, the overall propagation coordinate being unimolecular (excluding initiation and termination steps) (Scheme 3.1) The most relevant counterpart of these unimolecular reactions is represented by reactions in which one step − in many cases the first − is an intermolecular radical addition to an appropriate functionalized acceptor (Scheme 3.2).
If the attacking radical contains an adequately placed radical acceptor functionality, the possibility of a radical cycloaddition is provided, offering a procedure to construct cyclic products from acyclic precursors. For this type of ring-forming process, in which twomolecular fragments are united with the formation of two new bonds, the term “annulation” has been adopted (Scheme 3.3). A. J. McCarroll, J. C. Walton, J. Chem. Soc. Perkin Trans. 1 2001, 3215−3229.
use of the oxidizing properties of ceric(铈) ammonium nitrate (CAN)(硝酸铵) to furnish radical-cation species 3-2 out of optically active 1-arylthiobicyclo[4.1.0]heptane(庚烷) 3-1 by single electron transfer (SET). Y. Takemoto, T. Ohra, H. Koike, S.-i Furuse, C. Iwata, J. Org. Chem. 1994, 59, 4727−4729.
Pericyclic周环 Domino Reactions The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocyclic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels−Alder reactions with 1,3-dipolar cycloadditions , no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed .
two successive [4+2] cycloadditions: an intermolecular Diels−Alder reaction of 4-1 and 4-2 to give 4-3 is followed by an intramolecular cycloaddition. The obtained 4-4 is then transformed into 4-5 (Scheme 4.1). F.-G. Klarner, U. Artschwager-Perl, W.-D. Fessner, C. Grund, R. Pinkos, J.-P. Melder, H. Prinzbach, Tetrahedron Lett. 1989, 30, 3137−3140
a domino [3+3]-sigmatropic rearrangement: the synthesis of the enantiopure antifungal antibiotic (−)-preussin (4-14) by Overman, from the amine 4-10 and decanal to give the iminium ion 4-11 (Scheme 4.3). This undergoes a [3+3]-sigmatropic rearrangement to provide 4-12, followed by a Mannich reaction with the formation of 4-13. W. Deng, L. E. Overman, J. Am. Chem. Soc. 1994, 116, 11241−11250.
Ene 反应 具有烯丙型氢原子的烯烃与具有缺电子重键的化合物发生的取代加成反应， 称为烯反应。例如： 反应机理一般是烯丙型烯烃与具有重键的化合物进行同面加成，经过一个 六电子的Hückel芳香体系过渡态形成产物。 在此反应中，烯丙型氢原子发生1， 5 --σ迁移，断裂一个旧的σ键而形成一个新的σ键，同时烯丙型烯烃的双键进行位移。烯反应类似于Diels-Alder环加成和烯丙型氢原子的1， 5 --σ迁移。但并非全部反应按这种协同机理进行。
Nazarov 环化反应 酸催化下双乙烯酮进行电环化反应生成环戊烯酮。
Prins 反应 在酸催化下，醛与烯烃加成得到1，3—二醇、不饱和醇或环状缩醛的反应，称为Prins 反应。