Sigmatropic Claisen

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. 

A thoroughly investigated reaction on the biosynthetic pathway to aromatics is the [3+3]-sigmatropic Claisen rearrangement from chorismic acid to prephenic acid (Figure 18.8). 

The metastable byproduct of [4+2] cycloaddition was detected when the reaction of cyclopentadiene with diphenylketene was (Equation (38)) was examined by low-temperature NMR experiment at — 30°C.67 The [4+2] cycloadduct was not observed at elevated temperature because easily isomerizes to [2+2] cycloaddition product via [3,3] sigmatropic (Claisen) rearrangement. This observation was supported by kinetic measurements NMR) and isolation of [4+2] cycloadduct.68 Mechanism proposed by Machiguchi and Yamabe was re-examined by Singleton.69... 

Before we embark on our journey into the world of six-membered transition states, I would like to speak briefly about one reaction, to illustrate how a transition state is drawn throughout the book. The enzyme-catalyzed transformation of chorsimate (2) to prephenate (3) is a classic example of a [3,3]-sigmatropic Claisen rearrangement6 (Scheme IV). As an old bond is being broken and at the same time a new bond is formed in the transition state, the transition state for the Claisen rearrangement of chorismate to prephenate would look more like transistion state A than like B. Still, for the convenience of following the bond connection event clearly, I prefer to draw the transition state like B. 

The Fischer indole synthesis. The Fischer acid-catalyzed conversion of an 7V-arylhydrazone 42 into an indole is one of the most powerful and versatile methods for the preparation of indoles . The mechanism involves a [3,3] sigmatropic Claisen-type rearrangement of a protonated enehydrazine tautomer 43 to give intermediate 44, which spontaneously cyclizes by loss of ammonia, probably via indoline 45, to an indole 46 (Scheme 27). For unsymmetrical ketones, two isomeric indoles are possible and the general result is that the indole derived from the more stable (usually the more highly substituted) enehydrazine is formed. 

The transposition of oxygen in allylic esters (R6 = alkyl, phenyl) or carbamates [R6 = N(CH3)2] has the same overall bonding changes as the thermal [3,3] sigmatropic Claisen or Cope rearrangements. Chirality transfer from C-l to C-3 is accompanied by 1,3 oxygen transposition (carbonyl O to allylic O ). 

The first step is a [3,3]-sigmatropic Claisen rearrangement with suprafacial transfer of the vinyl group across the allyl part of the molecule. Then there is a simple reduction and tosylation. 

Recently, Wipf and Ribe reported a novel tandem process in which water accelerates both a sigmatropic Claisen rearrangement catalysed by Erker s catalyst and a subsequent carbometallation reaction with trimethylaluminium providing optically active phenols. Examples of this tandem process are shown in equations 148-150. 

The next stage occurs on heating the triene 67 with ethyl acrylate. First a Diels-Alder reaction 68 with the orientation and enzfo-stereoselectivity expected of this famous process gives an adduct with only two alkenes positioned so that it undergoes a [3,3]-sigmatropic (Claisen-Ireland) rearrangement 69 to give the product 70 with only one alkene. 

Several variants of [3,3] sigmatropic Claisen-type rearrangements have been used for the stereoselective synthesis of di- and trisubstituted olefinic systems 11,28,279,28°. 

In 1940 Carroll reported the rearrangement of P-keto allyl esters (49) followed by decarboxylation to yield y,5-unsaturated ketones (53) via a [3,3]-sigmatropic (Claisen) rearrangement (Scheme 4.13) [31]. The reaction has found limited scope in organic synthesis due to the harsh conditions required (130-220 °C) to induce the rearrangement. 

Despite the plethora of examples to choose from. Figure 18.6 outhnes those diverse cases, which are aromatic sigmatropic Claisen rearrangements in which the migrating group migrates to an aromatic nucleus, applied to the synthesis of natural products. 

The initial reaction of diphenylketene with cyclopentadiene at low temperatures affords the [4+2] cycloadduct 131, which subsequently undergoes a [3,3] sigmatropic (Claisen) rearrangement to give the isolated Staudinger reaction product 132 . ... 

In both cases, very good yields went along with excellent selectivity. In a very simple approach to divert a 3,3-sigmatropic Claisen process into a 2,3-Wittig rearrangement, the carbonyl group of 401 was replaced by its dimethylhydrazone (see 404). 

The synthesis of the branched-chain conduritol 103 by treating the alcohol 104 with N,N-dimethylacetamide dimethylacetal to effect a [3,3]-sigmatropic Claisen rearrangement has been described. 

The strategy for the synthesis of benzannulated enyne-allenes includes the use of Lewis acids to catalyze the [3,3]-sigmatropic Claisen rearrangement, which is promoted by AgBp4 at 25°C [280]. 

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