By Grob fragmentation

Vamos M, Ozboya K, Kobayashi Y (2007) Synthesis of bicyclic pyroglutamic acid featuring the Ugi reaction and a unique stereoisomerization at the angular position by Grob fragmentation followed by a transannular ketene [2-1-2] cycloaddition reaction. Synlett 1595-1599. Kreye O, Westermann B, Wessjohann LA (2007) A stable, convertible isonitrile as a formic acid carbanion [-COOH] equivalent and its application in multicomponent reactions. S3mlett 20 3188-3192... 

The pioneering woik of Ohloff in this field is shown by his historic paper on the synthesis of both (118) and (119). Inter alia, the bicyclic tosylate (121) provides, by Grob fragmentation, the unsaturated ketone (122), which also has a strong musk odour. 

Xiong, Q., Wilson, WK, and Matsuda, S.P. 2006. An Arabidopsis oxidosqualene cyclase catalyzes iridal skeleton formation by Grob fragmentation. Angew Chem Int Ed Engl 45 1285-1288. 

Most diaziridines are not sensitive towards alkali. As an exception, diaziridines derived from 2-hydroxyketones are quickly decomposed by heating with aqueous alkali. Acetaldehyde, acetic acid and ammonia are formed from (162). This reaction is not a simple N—N cleavage effected intramolecularly by a deprotonated hydroxy group, since highly purified hydroxydiaziridine (162) is quite stable towards alkali. Addition of small amounts of hydroxybutanone results in fast decomposition. An assumed reaction path — Grob fragmentation of a hydroxyketone-diaziridine adduct (163) — is in accord with these observations (B-67MI50800). 

It should be noted that the Grob fragmentation reaction and the reductive cyclization (homoallylation) discussed in this section involve the same oxanickellacyclopentane 66 as a common intermediate (Scheme 17). The reversibility of these C - C bond cleavage reaction and C - C bond formation reaction is also supported by the isolation and characterization (by X-ray analysis) of an oxanickellacyclopentane-like 66 (without a tether), which is prepared from a stoichiometric amount of Ni(cod)2, a diene, an aldehyde, and a monodentate phosphine ligand [41]. 

The [i,y fragmentation is known as Grob fragmentation. Its synthetic application is usually in the construction of medium-sized rings by fragmentation of fused ring systems. 

The cyclodextrin-supported cleavage of 1,3-oxathianes with IBX (cf Scheme 76, Section 8.11.6.4.6) <2006SC3771>, as well as the copper-catalyzed aminolysis of 1,3-dithianes <2006OL2547> has been published. l,3-Dioxane-2-ones readily undergo a Grob fragmentation (Equation 100) <2006CC4303>. This reaction is catalyzed by Ni- (24-99% yield) or by Pd-complexes (42-93% yield). 

Table 13. Cycloheptenones by Grob- Wharton Fragmentation of Bicyclo[3.2.0]heptan-l-ol Derivatives...

The Formation of Unsaturated Groups by Heterolytic Fragmentation , K. B. Becker and C. A. Grob, in Chemistry of Double-Bonded Functional Groups , ed. S. Patai, Wiley, New York, 1977, vol. 2, pp. 653-723. 

Suggest a mechanism for the transformation of 1 into 2, which has been described as a "Sml2-promoted Grob-fragmentation reaction. followed by an in situ, stereocontrolled Sml2-mediated cyclisation "... 

A possible reaction course comes to mind. The A-vinyl-2-pyrrolidone also possesses at the oxygen a nucleophilic center which could attack the electrophilic carbene carbon and could release the carbene ligand from the metal. The intermediate product formed—irrespective of whether it is an open chain or a six-membered ring—then undergoes a heterolytic fragmentation by splitting similar to that observed by Grob (84) (Fig. 7). 

This modification resulted in a yield improvement for the pentacyclization process from 47 % to 66 %. Treatment of the amino ether 192 with diisobutylaluminum hydride in refluxing toluene accomplished Eschenmoser-Grob fragmentation and reduction of the initially formed immonium ion, to give the unsaturated amino alcohol 193 in 86% yield. It was gratifying to find that 193 was the only product formed in this reaction. In the tetrahydropyran derivative, reduction of 192 to 193 is accompanied by about 15 % simple elimination. Displacement of the tosyl group in 196 gives sulfide 197, which is oxidized to sulfone 198. This material is metallated and coupled with enantiomerically pure aldehyde to secure the codaphniphylline skelton [74]. 

One of the very rare cases where a triple bond is formed by a normal Grob fragmentation is described by Corey in the course of the synthesis of hybrida lactone (45), an eicosanoid, isolated fix)m the marine alga Laurencia hybrida. The strained enol tosylate (43) yields the ethynyl ketone (44) under very mild... 

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