Dreiding synthesis

Karpf and Dreiding arrived at modhephene by thermal a-alkynone cyclization (Scheme XCIII) The synthesis of key intermediate 792 was unfortunately plagued by isomer problems. Also, the pyrolysis of 792 did not afford 786 cleanly. With the availability of this last intermediate, arrival at modhephene followed earlier precedent. 

A three-carbon unit can be introduced on ketosugars under Reformatsky conditions, as recently demonstrated by several groups [33,34], The analogous Dreiding-Schmidt procedure has also been applied in this case with successful double stereodifferentiation [35]. This is exemplified on ketone 18 which yields lactone 20 as a single isomer (see Scheme 10). The condensation on ketosugars of trimethylsilylacetate [36] or acrylate [33], in the presence of fluoride ion, has also been used with success for the synthesis of P-hydroxy acids or ra-methylene-y-lactones, respectively. 

The first total synthesis of betalains was announced in 1975 by Hermann and Dreiding (11), and it was later considerably improved by the same group. An independent synthetic approach to betalain pigments was developed by Buchi and co-workers (12). The enzymatic synthesis of betalains has not yet been investigated. Also, the physiological aspects of their formation are still poorly understood, despite the fact that numerous investigations have been carried out, for example, on their photoregulation and hormonal control (73). Betalains have recently received much attention by the food industry as the red to violet beta-... 

Only a few examples of intramolecular ene reactions of 1,7-enynes are known. Pyrolysis of terminal alkyne (131) in toluene for 48 h at 255 C results in 17% conversion to ene adduct (133). Ester (132) is more reactive, giving ene adduct (134) in 85% yield on heating for 62 h at 225 C. Ficini and coworkers have found that similar reactions can be carried out conveniently by flash vacuum pyrolysis. Pyrolysis of (135) at 420 "C at 200 Torr gives 80% conversion to ene adduct (136), a model for the synthesis of the a ring of lS,25-dihydroxycalciferol. Dreiding found that flash vacuum pyrolysis of ynone (137) at 550 °C gives ene adduct (IM) in 15% yield along with other products. 

Loeffler, A., Pratt, R. D., Pucknat, J., Gelbart, G., Dreiding, A. S. Preparation of a-methylenebutyrolactones by the Reformatskii reaction synthesis of protolichesterinic acid. Chimia 1969, 23, 413-416. 

The first preparative use of intramolecular C—insertion in organic synthesis was developed by Dreiding, who reported in 1979 that, on flash vacuum pyrolysis, a conjugated alkynyl ketone such as (36) is smoothly converted to a mixture of the cyclized enones (37) and (38) (equation 15). This elegant reaction apparently proceeds via isomerization of the alkyne to the corresponding alkylidene carbene. 

Intramolecular C—insertion is, essentially, a method for specific remote functionalization of hydrocarbons. An important implication of this for synthetic strategy is that the C—H insertion process can dissolve symmetry, thus leading from a simple precursor to a much more complex product. Both the clovene synthesis, by Dreiding, and the pentalenolactone E synthesis, by Cane, take advantage of this idea. It is further illustrated by the pentalenolactone E synthesis reported by Taber (Scheme 1). In the key step, P-keto ester (139), which has a single stereogenic center, is transformed into the tricyclic ketone (140), which has four stereogenic centers. 

Hermann, K., and Dreiding, A.S., Total synthesis of betalaines, Helv. Chim. Acta, 60, 673, 1977. 

Although a number of syntheses of the angular triquinane sesquiterpene isocomene (18) have now been published, the synthesis by Dreiding et al. is interesting since it features the sequential alkynone cyclisations (14)— -(15) and (16)——(17) as the two key 5-ring annulation reactions. In a new synthesis of the related sesquiterpene silphinene (23) intramolecular(2+2] photocycloaddition from (19) is first used to elaborate the tricycle (20), which on brief exposure to iodotrimethylsilane produces (21). Reduction of (21) to (22), and functional group elaboration then completed the... 

Several spectacular syntheses of the sesquiterpene sativene (51) have been published in the past, but few are more interesting than the one now described by Dreiding et al. This synthesis uses the novel conversion of (48) to (50), involving addition of buta-1,2-dienyltitanium, then acid treatment, and in situ intramolecular [4+2] cycloaddition of the resulting cyclopentadiene allene derivative... 

Schlessinger et al. have outlined a new approach to pentalenolactone (71), which has as a key step the conversion of (69) to (70) by intramolecular acylation, and Karpf and Dreiding describe an intriguing design for the synthesis of the propellane natural product, modhephene (74), based on the thermal or-alkynone cyclization (72) - (73). 

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