Unsaturated compounds Claisen rearrangement

The product is a y,8-unsaturated carbonyl compound (a 1,5-diene), hinting that the last step is a Claisen rearrangement. 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

Some applications of the thio-Claisen rearrangement to the syntheses of thiocarbonyl compounds, particularly unsaturated dithiocstcrs and thionesters, and of its stereocontrol aspects are reviewed in [120]. A particularly high stereoselectivity was observed with S-allyl derivatives of P-hydroxydithioesters syn products were obtained exclusively, according to the accompanying scheme [495,496]. 

The aliphatic Claisen Rearrangement is a [3,3]-sigmatropic rearrangement in which an allyl vinyl ether is converted thermally to an unsaturated carbonyl compound. 

The aliphatic Claisen rearrangement is simpler in that there is no rearomatisation at the end but there is an ionic step first as the vinyl ether 67 has to be made and the easiest way to do that is from the allylic alcohol 65 by acetal exchange with another vinyl ether to give 66 and elimination to give 67. All these steps, including the rearrangement occur under the same conditions16 and the product is a y,S-unsaturated carbonyl compound 68. 

Allylic C-H insertions have been used in key steps of the enantioselective synthesis of the pharmaceuticals (+)-ceitedil (26) [21] and (+)-indatraline (27) [22] (Scheme 11). The allylic C-H insertion reaction is an exciting alternative to the Claisen rearrangement as a rapid method for the synthesis of y,c>-unsaturated ester [23 ]. Similarly, the allylic C-H insertion with vinyl silyl ethers generates protected 1,5-dicarbonyl compounds, a complimentary reaction to the Michael addition [24]. Both types of C-H insertion can be achieved with high diastereoselectiv-ity and enantioselectivity [23, 24]. 

Ireland-Claisen rearrangements are extraordinarily interesting from a synthetic point of view for several reasons. First, the Ireland-Claisen rearrangement is an important C=C bondforming reaction. Second, Ireland-Claisen rearrangements afford y,<5-unsaturated carboxylic acids, which are valuable bifunctional compounds. Both of the functional groups of these acids can then be manipulated in a variety of ways. 

Claisen Rearrangement Section 22.9 Cleavage of a tert-Butyl Ester in Acid Section 23.3 Conjugate Addition to a,/3-Unsaturated Compounds Section 18.10... 

The Claisen rearrangement is a general synthesis of y,5-unsaturated carbonyl compounds... 

The Claisen rearrangements of allyl vinyl ethers yield y, 8-unsaturated carbonyl compounds. When R = NR2 the rearrangement is known as the Eschenmoser-Claisen... 

The Claiscn rearrangement of allyl vinyl ethers is usually an irreversible reaction due to the energetic benefit of forming aC-O double bond. However, in strained bicyclic systems the retro-Claisen rearrangement (3-oxa-Cope rearrangement) of y,<5-unsaturated aldehydes has been observed32. Sometimes equilibrium mixtures of vinyl ether and carbonyl compound were found. For example, the ratio of the valence tautomers, bicyclo[3.1.0]hex-2-ene-6-cWo-methanal to 2-oxabicyclo[3.2.l]octa-3,6-diene, is approximately 7 333. Nevertheless this reaction was used in the preparation of a key intermediate in a prostacyclin synthesis34. 

The treatment of vinyl anions with elemental selenium also leads to seleno-carbonyl compounds via eneselenolate anions (Eqs. 4-6). Deprotonation of l,3-selenothio-2-thione with EDA followed by the reaction with elemental selenium proceeds accompanied with the rearrangement of vinylic skeleton to form l,3-dithio-2-selone derivatives (Eq. 4) [38]. The vinyl anions from oxa-zolines and imidazoles were treated with elemental selenium to give the oxazo-line selone and imidazoline selone after the aqueous workup (Eq. 5) [39]. The reaction of vinyl magnesium halides with elemental selenium and allyl bromide gives allyl vinyl selenides that undergo a seleno-Claisen rearrangement to generate y,6-unsaturated selenoaldehydes (Eq. 6) [40]. 

The Claisen rearrangement of allyl vinyl ethers 480 is a fairly general method for the preparation of y, -unsaturated carbonyl compounds of the general formula 481 from simple precursors (Scheme 2.154). ° Synthetically, this transformation is equivalent to the well-known a-allylation of enolates, which gives ultimately the same product. However, the mechanisms and conditions of these two reactions differ and their synthetic potentials are complementary to each other. 

The synthetic utility of this process can be seen by evaluating the examples in Table 2. For example, because the cyclopropane serves as a pseudo alkene and because the [1.5] shift requires a six-memb ed transition state, it relates conceptually to the Cope and Claisen rearrangements. The 7,8-unsaturated carbonyl compounds in Table 2 are those that would otherwise be obtained via Claisen or orthoester Claisen rearrangements, which are normally effected under strongly acidic or strongly basic conditions (Scheme 3). 

Lewis acid-mediated reactions can be classified into two groups (Fig. 4). In the first (type 1) the complex between substrate and Lewis-acid reagent produces the product. Claisen rearrangement promoted by a Lewis-acid catalyst is a typical example of this type. Some complexes formed between Lewis acids and substrates are, however, stable enough to react with a variety of reagents from outside the system to generate the product (type 2). The Diels-Alder reaction between Lewis acid-activated unsaturated carbonyl compounds and dienes is an example of type 2 reactions. 

Application of Claisen methodology led to a number of successful total syntheses of natural compounds. Thromboxane B2 has been synthesized from a 4,5-unsaturated sugar derived from D-glucose [126]. The Ireland-Claisen rearrangement [127] is also the key reaction used to control the introduction of the right wing of pseudomonic acids [128]. 

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