Diels-Alder reaction Claisen rearrangement

Rearrangement reaction Addition reaction Diels-Alder reaction Claisen reaction Substitution reaction Elimination reaction Wittig reaction Grignard reaction... 

FIGURE 2.32. Representative processes mediated by hydrogen-bond donors nucleophilic additions to (a) carbonyls, (b) imines, (c) epoxide, (d) hetero-Diels-Alder, (e) Claisen rearrangement reactions, and (f) Michael additions. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Tables 12.1-12.3 below give some examples of the magnitude of each term for two bimolecular reactions (Diels-Alder and Sn2 reactions, forming either one or two molecules as the product) and a unimolecular rearrangement (Claisen reaction). All values have been calculated at the MP2 level with the 6-31G(d) basis for the Diels-Alder and Claisen reactions, and the 6-31+G(d) basis for the S l reaction. The values are given in kcal/mol at a temperature of 300 K (RT = 0.60 kcal/mol).

Like the Diels-Alder reaction discussed in Sections 14.4 and 14.5, the Claisen rearrangement reaction takes place through a pericyclic mechanism in which a concerted reorganization of bonding electrons occurs through a six-membered, cyclic transition state. The 6-allyl-2,4-cyclohexadienone intermediate then isomerizes to o-allylpbenol (Figure 18.1). 

Two other important sigmatropic reactions are the Claisen rearrangement of an allyl aryl ether discussed in Section 18.4 and the Cope rearrangement of a 1,5-hexadiene. These two, along with the Diels-Alder reaction, are the most useful pericyclic reactions for organic synthesis many thousands of examples of all three are known. Note that the Claisen rearrangement occurs with both allylic aryl ethers and allylic vinylic ethers. 

Claisen rearrangements with 74 -, Diels-Alder reactions with 74 -, enantioselective reactions 74... 

Catalysis by lithium perchlorate in dichloromethane Diels-Alder reactions and 1,3-Claisen rearrangements [100]... 

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

Due to the AV (volume change of activation) of Claisen rearrangements having a negative value, as in the Diels-Alder reactions, the Claisen rearrangement reaction is expected to be accelerated by water according to the same effect.151,152... 

Neier and coworkers have used a domino Diels-Alder/Ireland-Claisen process for the synthesis of (rac)-juvabione 4-46 and (rac)-epijuvabione [15]. Since neither the Diels-Alder reaction of the acetal 4-44 and methyl acrylate nor the sigmatropic rearrangement seemed to be stereoselective, these authors obtained the cyclohexene derivative 4-45 as a mixture of three diastereomers (Scheme 4.9). 

Some other ring expansions involving the intramolecular amino Claisen rearrangement of vinylarylaziridine [ 123], the Diels-Alder reaction of indoles with acetylene derivative [124-127] and the dibromocarbene insertion into quinoline enol ethers [ 128] have been used to prepare 1-benzazepines. On the other hand, treatment of 3-chloro-3-phenyl-l,2,3,4,5,6-hexahydro-l-benz-azocin-2-ones with piperidine causes a ring contraction to give 2-phenyl-2-(l-piperidinylcarbonyl)-2,3,4,5-tetrahydro-l//-l-bcnzazepines in an excellent yield [23]. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

---