Grob-type fragmentation

It was suggested that benzonitrile (28) is formed from the Zf-conformer (31) in a Grob-type fragmentation <69AG543> and the isothiocyanate (27) is formed from the Z-conformer (32) in a Curtius rearrangement. 

Grob-type fragmentations induced by nucleophilic attack of Nhfr on the carboxyl group of quaternary /J-aminoaldcliydes and jS-aminoketones (119) have been reported (Scheme 14)." /V-(2-lmino-1 -oxopropyl)glycinc is fonned as an intennediate in the base-catalysed decomposition of (A -X)-Ala-Gly.100... 

Compound 403 is readily reduced with sodium borohydride at -78°C and yields the monoalcohol 405 (115). It also reacts with potassium t -butyl hydroperoxide at -20°C and gives the cis-enone-perester carbonate 406 in high yield (116). This last transformation can be explained by retro-Claisen fragmentation of intermediate 407 followed by the elimination of methoxide ion from 408. It is also possible that 407 undergoes a direct stereoelectronically controlled Grob type fragmentation to compound 406. 

Ozonolysis of diketone carbonate 417 in methanol afforded an almost quantitative yield of the bicyclic diene triketone hydroxy-ester 418 (119). This remarkable transformation can also be readily explained. Ozonolysis of 417 produces the tetraketone intermediate 419 followed by methanol addition to produce the hemi-ketal 420 which undergoes a retro-Claisen reaction to 421. Then, loss of carbon dioxide from 421 yields 418. Again, 420 could also undergo a Grob type fragmentation to yield 418 directly. 

A problem of considerable difficulty in this synthetic sequence (Eq, 21) has been the preparation of the exceedingly sensitive a-hydroperoxy acids (13) that serve as precursors to the a-peroxylactones. Unfortunately these substances undergo readily base- and acid-catalyzed Grob-type fragmentations (Eq. 22) and must, therefore, be prepared under mild, preferably neutral, conditions. The successful routes are summarized in Eq. 23. 

Unsymmetrical alkenes can be prepared by mixed intermolecular reactions if one of the components, commonly acetone, is used in excess (equation 83). As the isopropyl group is a common subunit of many terpenes this method provides a valuable route for its introduction. Pattenden and Robertson used such a reaction followed by a Grob-type fragmentation in their preparation of the daucenone (42) from the readily enolized ketone (43). The bicycle (42) was used as an intermediate for the synthesis of the diterpene ( )-isoamijiol (44 equation 84). Mixed couplings are not restricted to acetone, and almost any carbonyl may be used. For example, Paquette et al. employed the aldehyde (45) in a synthesis of ( )-a-vetispirene (46 equation 85). More complex mixed couplings are also possible. For example, the aldehydes (47) and (48) are coupled efficiently to the stilbene (49), which in turn is converted to phenan-threne alkaloids such as atherosperminine and thalictuberine (equation 86). ... 

The reaction of cis- and fra j-methyl-substituted l-(trimethylsiloxy)bicyclo[n.l.O]alkanes (n = 3,4,5) is stereospecific. When treated with lead(IV) acetate, followed by diazomethane, these substrates give the methyl ( )- and (Z)-alkenoates, respectively. The reaction is interpreted by assuming electrophilic attack of lead(IV) acetate on the cyclopropane carbon to cleave the ring, followed by a Grob-type fragmentation with lead(II) acetate as the leaving group. 

A recent synthesis of piperolein A (128) utilized an aldol-Grob type fragmentation with piperonal, cyclohexanone, and 13-propanediol to give an ester which was readily transformed into the amide [404]. Piperolein B (129) was found to display larvacidal activity against second stage larvae of the dog roundworm Toxocara canis [405]. 

The bis-trimethylsilyl ethers of stereoisomeric 5,7-undecanediol 78 (as well as the free diols) give upon chemical ionization (protonation with QH9) MH+ ions, which show two major processes (reaction 41). One corresponds to a Grob-type fragmentation 05-cleavage) of the ion 79 (formed by loss of Me3SiOH from protonated 78) to yield the silylated aldehyde 80. The second major reaction path involves loss of CH4 from MH+, followed by cyclization of the intermediate 81 (siloxy transfer) to 82 and ft-cleavage (loss of 1-hexene) to generate 8467. This reaction sequence, in which a centrally located structural unit rather than a peripheral one is eliminated, is rarely observed under chemical ionization and deserves further study. 

An aldol condensation/Grob-type fragmentation sequence, originally disclosed by Nagumo et al. [139] and illustrated by the example depicted in Scheme 15, was found by Strunz and Finlay to provide convenient synthetic access to pipercide, 50(n=4), piperolein A, 35(n=4), and other... 

This reductive alkylation was used in a synthesis of 8, which contains the 10-membered ring system of germacrane sesquiterpenes. Thus the tetralonc 5 was converted by way of 6 into the tosylate 7. On treatment with LDA in THF at 24°, 7 underwent a Grob-type fragmentation to give 8. 

Fragmentation of five-and six-membered rings. Semmelhack and Tomesch have reported a mild and efficient Grob-type fragmentation. The reaction of 1,2-epoxycyclohexane (I) with the anion of bis(phenylthio)methane (6, 267) gives... 

Grob-type fragmentation, 154—155 Ground-state spectroscopies, 213—220 Ground-state theory, 207—210 GSH. See Glutathione (GSH)... 

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