Claisen rearrangement-ene reaction

In the laboratory of T. Nakai, the asymmetric tandem Claisen-rearrangement-ene reaction sequence followed by a modified McMurry coupling was used to access (+)-9(11)-dehydroestrone methyl ether. The Claisen-ene product was subjected to ozonolysis and epimerization to the 8,14-anf/ configuration. The C-ring was constructed by treating the tricyclic diketo aldehyde with TiCl3-Zn(Ag) in DME to afford the desired final product in 56% yield. 

For an application of this method in the steroid total synthesis by a tandem Claisen rearrangement-ene reaction see ref 523. 

As mentioned previously, the Chugaev elimination has found particular use in the field of terpenoid chemistry, not only in structural studies, but also in synthesis. For example, a tandem Claisen rearrangement-ene reaction of geraniol derivative 23 gave... 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Claisen or Cope rearrangement Ester cracking Conia ene reaction... 

This reaction also is concerted and proceeds via a six-membered transition state, but here the species (59), corresponding to the ene-one intermediate (53a) in the aromatic Claisen rearrangement, is in fact the end-product. This is so because there is in (59) no energetic driving force, comparable to re-aromatisation in (53a— 52a), to promote its enolisation. 

A simple synthesis of fluorenes as 4-297 was developed by Schafer and coworkers, also using a combination of a Claisen rearrangement and a carbonyl ene reaction (Scheme 4.63) [100]. Heating 4-295 in xylene at 180 °C led to 4-297 as a single diastereomer in 73 % yield the phenol 4-296 can be assumed as an intermediate, but this could not be detected in the reaction mixture. 

Shortly after these results were published, Giguere and coworkers reported dramatic reductions in reaction times in other MW-assisted syntheses, including Diels-Alder, Claisen rearrangements and ene reactions [2]. These reactions were also performed at elevated pressures, but sealed glass vessels (inside a bath packed with ver-miculite) were used rather than Teflon. 

Two main mechanistic hypotheses were considered for this reaction type38, a zinca ene 39 reaction and a metallo-Claisen rearrangement (equations 31 and 32). 70 and 71 are drawn as monomers for the sake of simplicity. The former probably exists in oligomeric form (see Section . . ), whereas the transition state of the metallo-Claisen rearrangement may involve two molecules of 7138. Since the simplified structures are perfectly suitable to rationalize the selectivity and reactivity of these reactions, they are used throughout this chapter. 

A zinca ene reaction is by definition (M. B. Smith and J. March, Advanced Organic Chemistry—Reactions, Mechanisms, and Structure, 5th edition, Wiley, New York, 2001, p. 1377) not a rearrangement, because it involves two different molecules. Nevertheless, reactions of the type described in equation 30 are included in this review regardless whether the authors rationalized them by a metallo-ene or metallo-Claisen pathway. This is justified since the original mechanistic assumptions were modified later (see Section II.A.3). 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone applies a tandem Claisen rearrangement and intramolecular ene-reaction. Most 19-nonsteroid contraceptive agents are produced by total synthesis from nonsteroidal starting materials. 

An interesting aspect of the allylic C-H insertion is that the products are y,6-unsaturated esters. Traditionally, y,6-unsaturated esters are most commonly prepared by a Claisen rearrangement, especially if stereocontrol is required. Diastereocontrol is also possible in the C-H insertion as long as the reaction occurs at a methylene site where there is good size differentiation between the two substituents [21]. An example is the reaction between 17 and the silylcyclohex-ene 18 which forms the C-H insertion product 19 in 88% de and 97% ee [21]. Other catalysts such as Rh2(.R-BNP)4 and Rh2(S-MEPY)4 have been explored for allylic C-H activation of cyclohexene but none were was as effective as Rh2(S-DOSP)4 [22]. 

The review covers uses of these reagents as catalysts for ene reactions, [2 + 4] and [2 + 2] cycloadditions. A few years ago (C2H5)2A1C1 was reported to catalyze also the Claisen rearrangement (yields, 89 96%).2... 

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