Intramolecular diyl trapping reaction

With the intent of exploiting the intramolecular 1,3-diyl trapping reaction, Little and Muller prepared azo compound 663 and decomposed the substance in refluxing acetonitrile (Scheme LXVI) Triquinane 664, isolated in 85% yield, was then degraded to a saturated ketone which was methylated in the angular position prior to olefination. 

During their studies on the stereochemistry of intramolecular 1,3-diyl trapping reaction as depicted in Scheme 13, Little and collaborators utilized the reductive decarboxylation in preparing the required compound 31.24 The usefulness of Barton decarboxylation was also realized by Braekman and colleagues during their studies on ichthyotoxic sesterterpenoids in providing the needed methyl ketone 32 from the carboxylic acid 33.25 Helmchen has developed an easy route to a stable... 

Table 5 Ring Junction Stereoselectivity in Intramolecular Diyl Trapping Reactions OH...

Intramolecular 1,3-Diyl Trapping Reaction (3/ , 3a/ , 6a/ , 7aS )-2,3.3a,5,6,6a,7,7a-Octahydro-2,2-dimethyl-17/-cyclopenta aJpentalen-3-ol Typical Procedure24 ... 

A second example of diastereoselection in intramolecular diyl trapping reactions is provided by diazene 12 (Tabic 2, entry 18)31. Heating to reflux in acetonitrile gives 85% of a single fused tricyclic product. In this process, two stereocenters control the formation of four new stereocenters. 

ABSTRACT In this chapter we describe the development and application of the intramolecular diyl trapping reaction (cycloaddition) to the total synthesis of hirsutene, capnellene, coriolin, and hypnophilin, as well as its application toward the synthesis of aphidicolin and an analog of taxol . 

With diazene 19 in hand, we were in a position to explore the first intramolecular diyl trapping reaction. These transformations are exceptionally easy to conduct, simply requiring heating or photolysis, removal of the solvent and isolation of the product(s). As with many diyl trapping reactions, the course of the process was monitored by TLC, reflux being discontinued when the diazene was consumed. In this... 

The intramolecular diyl trapping reaction was studied in a variety of solvents (THF, MeOH, acetonitrile), and the diyl was generated both thermally and photochemically [14]. The photo-induced deazetation of 41 in methanol at -6 °C afforded the desired tricyclopentanoid 40 in an excellent 84% yield. The transition state model portrayed by 49 nicely rationalizes the stereochemical outcome. The solvent study revealed that its choice had essentially no effect upon the product ratio at any given temperature. However, we did discover that methanol, a solvent which had not been utilized previously in intramolecular 1,3-diyl trapping reactions, was very useful for low temperature studies. 

To test the proposed route we capitalized upon our ability to use the intramolecular diyl trapping reaction to synthesize 95, the mono-ketal analog of 143. Ozonolytic cleavage of the C-C n bond of 95 followed by reduction with NaBIfy afforded diol 145 in an 85% yield. The primary alcohol was selectively protected as a silyl ether, and the secondary alcohol oxidized with PCC to provide ketone 146 as a 1 1 mixture of diastereomers. 

While the sequence just outlined has been carried out using the monoketal 95, rather than the bisketal 143, we believe that it will also be applicable to the latter. In fact, we have managed to utilize the intramolecular diyl trapping reaction to synthesize 143 and have, in preliminary experiments, demonstrated that it is possible to selectively convert the exocyclic ketal to a methyl ketone 151, as is needed to synthesize aphidicolin (89) [57]. At this time we are perfecting our route to diazene 144 and anticipate that the natural product is finally within our grasp. 

R.D.Little, The Intramolecular Diyl Trapping Reaction. A Useful Tool for Organic Synthesis, Chem.Rev., 1986, 86, 875. 

Little and his co-workers have extended the usefulness of their diyl-trapping reaction by the introduction of sulphone residues, and the intramolecular Wittig and Wadsworth-Emmons reactions have been found to be useful in the synthesis of bicyclo[3.3.0]oct-A -en-3-ones[e.g. (75) (76), and (77) - (78)]. 

Little, R.D. and Carroll, G.L. (1981) Intramolecular 1,3-diyl trapping reactions total synthesis of marine natural product ( )-A -capnellene. Tetrahedron Lett., 22, 4389-4392. 

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