Alder Strategies

A similar intramolecular Diels-Alder strategy was employed in an efficient synthesis to an appropriately functionalized hydrindanone nucleus (212). After functionalization, Diels-Alder cyclization, and appropriate functional group manipulation, this hydrindanone was converted into ( )-cortisone. The overall process afforded ( )-cortisone in a total of 18 chemical steps in approximately 3% yield. 

Fallis A. G. From Tartrate to Taxoids a Donhle, Intramolecnlar Diels-Alder Strategy Pure Appl. Chem. 1997 6, 495-500... 

As can be seen below, a retro-Diels-Alder strategy was used to prepare 2,3- and 2,4-disubstituted furans with a SF5 group as one of the substituents, which was introduced into furan ring for the first time <06OL5573>. 

Several ingenious syntheses of natural products have been developed by exploiting benzcyclobutene ring opening to o-quinodimethane. Particularly, the intramolecular Diels-Alder strategy employing o-quinodimethane intermediates has been very effective for the construction of polycyclic structures. Selected examples are gathered in Table 12. 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

Retro-Diels-Alder strategy, 21 148 Retro-ene reactions, 21 150 Retrofit (revamp) design, 20 724 Retrofitted passive heat-transfer... 

Many groups have employed a Diels-Alder strategy toward the synthesis of the well-known antitumor compound paclitaxel, which has a tetracyclic core containing two... 

Jimenez-Alonso S, Estevez-Braun A, Ravelo AG, Zarate R, Lopez M (2007) Double domino Knoevenagel hetero Diels-Alder strategy towards bis-pyrano-l,4-benzoquinones. Tetrahedron 63 3066-3074... 

J. C. Lopez, A. M. Gomez, and B. Fraser-Reid, Silicon-tethered radical cyclization and intramolecular Diels-Alder strategies are combined to provide a ready route to highly functionalized decalins, J. Chem. Soc. Chem. Comtmm. p. 762 (1993). 

Lei, B. and Fallis, A.G., Direct total synthesis of (+)-longifolene via an intramolecular Diels-Alder strategy,... 

Sequential Grubbs metathesis/Diels-Alder strategies can be used to produce tetrahydroquinolines. For example, intramolecular enyne metathesis followed by reaction with alkynes followed by oxidation serves as a useful route to multisubstituted systems (Scheme 78) <2000CC503>. 

Piperidines can be produced stereoselectively with diastereomeric excess of >95% and in moderate yield using a three-component Diels-Alder strategy. A chiral auxiliary is required as part of a l-aza-4-borono-l,3-diene and the reaction was reported as a solid-phase synthesis with acceptable outcomes (Scheme 92) <2003CEJ466>. 

Scheme 17.17 Smith s asymmetric Diels-Alder strategy to phenylsulfcne 57.

Pericyclic reactions in the synthesis of heterocycles 87YGK60. Pummerer reaction in the synthesis of heterocycles 89KGS1299. Retro-Diels-Alder strategy in the synthesis of heterocycles 87S207. Solid-phase synthesis of heterocycles 89BSF237. 

Several examples of alkynic ketone formation have been recorded since Weinreb s first examples. A Diels-Alder strategy for Ae synthesis of mevinolin required the preparation of alkynic ketone (24). Standard methods, calling for the addition of the alkynide anion to an aldehyde followed by oxidation, lead to extensive degradation and by-product formation. The Weinreb methodology was clearly more effective (Scheme 8). ... 

Ichihara, A. Retro-Diels-Alder strategy in natural product synthesis. Synthesis 1987, 207-222. 

Marsault, E., Toro, A., Nowak, P., Deslongchamps, P. The transannular Diels-Alder strategy applications to total synthesis. Tetrahedron 2001,57,4243 260. 

These examples illustrate both the utility and the limitations of the rearrangement as part of a synthetic strategy. These may be summarized in the following terms. Firstly, there are many powerful methods with well-established regiospecificity that lead to the bridged ring system of defined stereochemistry, for example the Diels-Alder strategy (Scheme 4). 

Barluenga and coworkcrs recently extended the scope of the reaction between nitroalkenes and dienes like 305 by varying the substituents on the nitroalkene as well as on the diene. The 4-nihocyclohexanone derivatives were generally obtained with good yields and very high enantiomeric excesses. This Diels-Alder strategy was used to synthesize cyclic -amino acids -" . 

The second Stork synthesis employed the same Diels-Alder strategy however, an intramolecular varient of the cycloaddition was utilized, as shown in Scheme 3.2. ... 

Transannular Diels Alder strategy applied to total synthesis (transformations of macroheterocyclic trienes) 01T4243. 

These nitroso compounds undergo [4 + 2] cycloadditions readily with 2,3-dimethylbutadiene to yield the expected adducts. This method was used to synthesize arylnitroso compound 11, which was in turn used to prepare a 3-pyrrolidinone via a Diels-Alder strategy (Scheme 3-V). The initial cycloaddition was apparently regioselective, giving only the isomer shown (cf. Scheme 3-III)."... 

In a recent investigation, Kibayashi et al. have used a nitroso Diels-Alder strategy in the synthesis of tropane alkaloids (Scheme 3-VIII).27 The initial cycloaddition of a-chloronitrosocyclohexane with 6-benzy-loxy-l,3-cycloheptadiene showed a 4 1 facial selectivity. The major isomer of this cycloaddition could be converted to pseudotropane and tropa-cocaine by a straightforward sequence of steps. 

The quinone Diels-Alder strategy gives rise to the proper stereochemistry at C(8) and C(14) and provides a e/s-fused BC ring system that ensures selective reduction of the C(7) carbonyl from the convex face of the molecule. Indeed, reduction of (301) with sodium borohydride in ethanol at 15 °C afforded (302). 

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