Carbonyl compounds from Claisen rearrangement

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. 

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. 

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. 

The efficient addition of allylic bromides to carbonyl compounds in a heated zinc column has been used to synthesize ( )-artemisia alcohol (81 R = H, X = CH2) in 91% yield.Artemisia ketone was synthesized efficiently from 3-methyl-l-trimethylsilylbut-2-ene and 3-methylbut-2-enoyl chloride in the presence of AlCls. Racemic methyl santolinate (82) was synthesized (along with the C-3 epimer ratio 8 1) via Claisen rearrangement, according to Scheme 2 (cf. Vol. 6, p. 7). ... 

In most of the examples of asymmetric Claisen rearrangements in the literature, a carbonyl compound is obtained starting from a chiral allylic alcohol with an excellent transfer of chirality. An example developed by Saucy and coworkers, shown in Figure 10.14, nicely illustrates this methodology [1639, 1645], Alcohol... 

This reaction was first reported by Johnson et al. in 1970. It is a highly stereoselective synthesis of y,5-unsaturated esters from the reaction between allylic alcohols and an orthoester in the presence of a trace amount of weak acid, such as propionic acid. Because this reaction is the modification or variant of the Claisen Rearrangement, it is often referred to as the Johnson orthoester Claisen rearrangement. Occasionally, this reaction is also known as the Claisen-Johnson orthoester rearrangement, " or Johnson orthoester protocol. This reaction involves the formation of mixed orthoester from allyl alcohol and the added orthoester, which loses an alcoholic component to form a ketene acetal then migrates to unsaturated carbonyl compounds via the Claisen Rearmagement with high syn selectivity. Posner further extended this reaction to use sulfonyl orthoester. Overall, this reaction has been applied to the synthesis of a variety of complicated natural products, such as squalenes. ... 

From a retrosynthetic point of view, the Meerwein-Eschenmoser-Claisen rearrangement shares the basic Claisen retron, a y,<5-unsaturated carbonyl compound, with other variants of the reaction. More specifically, its retron consists of a two-carbon chain branching off an allyhc stereocenter and terminating in an amide or a functional group derived thereof Such a motif can be readily identified in numerous natural products and other synthetic targets. 

Ester enolate have been generated under dissolving metal conditions with the reduction of a-halo carbonyl compounds. For example, the use of freshly activated Zn dust following Reformatsky protocol leads to the Claisen rearrangement of zinc enolate derived from 123 to yield acid 124. 

Finally, and as pointed out in Scheme 8.101 (Chapter 8), there is an aromatic version of the Claisen rearrangement. As the ketone intermediate is conjugated (prior to its tautomerization to the corresponding phenol), the process may be considered an addition to an unsaturated carbonyl compound. Equation 9.35 represents the aromatic Claisen rearrangement, which, as shown from left to right, allows the conversion of an arylvinyl ether into a substituted phenol. 

The Claisen rearrangement of vinyl allyl ethers is a powerful reaction for the preparation of yS-unsaturated carbonyl compounds. The regioselectivity of the ketal version of this reaction has been studied, the results aiding the understanding and prediction of products formed from ketals of unsymmetrical ketones [equation (34)]. The allyl vinyl ether may also be formed by proto-... 

PhenyIthioallyl alcohols are produced in high yields from carbonyl compounds and 1-phenylthiovinyl-lithium. Successful Claisen and Carroll rearrangements can be carried out leading to y-keto-aldehydes and 1,4-diketones, respectively, after hydrolysis (Scheme 17, p. 84). ... 

In retrosynthetic analysis, we recognize the need for the Claisen rearrangement when we see a y,6-unsaturated carbonyl compound. Compound 8.19 contains unsaturation y, 6 to the bromo-functional carbon. Consider a carbonyl compound as a likely intermediate and then write a retro-Claisen rearrangement (Scheme 8.19). The ketene acetal could come from ethyl orthoacetate. Continue with a disconnection at the alcohol. The actual synthesis is shown in Equation 8.37 [52]. 

The cascade process combining the [Ira(cod)]2-catalyzed vinylation and the Claisen rearrangement was also reported (Scheme 5.35) [35]. This one-pot approach could be applied for the synthesis of Y,S-unsaturated carbonyl compounds 51 from allyl alcohols 49 and vinyl or isopropenyl acetates 50. 

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