Fragmentation reactions stereochemistry

Fragmentation reactions can also be used to establish stereochemistry of acyclic systems based on stereochemical relationships built into cyclic reactants. In both the examples shown below, the aldehyde group generated by fragmentation was reduced in situ. 

The evidence for such a mechanism results from both the reaction stereochemistry and also from the observation of minor diphenyltoluene by-products (Scheme 8). The major pathway is outlined using heavy arrows. This can be seen to afford the stereospecificity of equations 14a and 14b. Additionally, each of the diradical intermediates and intermediate excited states—B, C, E, F and G—undergo a minor extent of internal bond fission [i.e. Grob or 2,3- (1,4) fragmentation] to afford a diphenyltoluene with the corresponding ring skeleton. The basis for the choice of a main pathway versus the minor ones comes from the observed stereochemistry. 

Most syntheses make the side-chain alkene by an elimination reaction so the first disconnection is an FGI adding HX back into the alkene. The last C-C bond-forming operation in most syntheses is an intramolecular aldol reaction to make the enone so that can be disconnected next. It is the starting material for the aldol, a simple monocyclic diketone, which is usually made by a fragmentation reaction because this is a good way to set up the stereochemistry. 

The stereochemical outcome of a reaction can suggest much about its mechanistic pathway. If a molecular fragment, whose stereochemistry is clearly defined, can be attached to the reactant and remain attached during the course of the reaction without affecting the chemistry, then determination of product stereochemistry can be straightforward using spectroscopic means. 

Fragmentation reactions may be used to prepare cyclic or acyclic alkenes from cyclic precursors. The stereochemistry of the alkene can be set up by controlling the relative stereochemistry of the cyclic substrate, a process that is normally relatively easy. The ketone 35, for example, an intermediate in a synthesis of juvenile hormone, was obtained stereospecifically from the bicyclic compound 33 using two successive... 

Stereochemistry chi 4 Intermediates and transition states in substitution reactions How substitution reactions affect stereochemistry What sort of nucleophiles can substitute, and what sort of leaving groups can be substituted The sorts of molecules that can be made by substitution, and what they can be made from fragmentation reactions ch36... 

Similar fragmentations to produce S-cyclodecen-l-ones and 1,6-cyclodecadienes have employed l-tosyloxy-4a-decalols and 5-mesyloxy-l-decalyl boranes as educts. The ringfusing carbon-carbon bond was smoothly cleaved and new n-bonds were thereby formed in the macrocycle (P.S. Wharton, 1965 J.A. Marshall, 1966). The mechanism of these reactions is probably E2, and the positions of the leaving groups determine the stereochemistry of the olefinic product. 

In the olivanic acid series of carbapenems the ( )-acetamidoethenyl grouping can be isomerised to the (Z)-isomer (19) (22) and reaction with hypobromous acid provides a bromohydrin that fragments to give a thiol of type (20) when R = H, SO H, or COCH. The thiol is not isolated but can react to provide new alkyl or alkenyl C-2 substituents (28). In the case of the nonsulfated olivanic acids, inversion of the stereochemistry at the 8(3)-hydroxyl group by way of a Mitsunobu reaction affords an entry to the 8(R)-thienamycin series (29). An alternative method for introducing new sulfur substituents makes use of a displacement reaction of a carbapenem (3)-oxide with a thiol (30). Microbial deacylation of the acylamino group in PS-5 (5) has... 

The reaction of carbon atoms with A-unsubstituted aziridines leads to alkenes and hydrogen cyanide (72IA3455), probably via extrusion from the initially formed adduct (285). The fragmentation does not appear to be concerted, although this would be a symmetry-allowed process, since only about half the alkene formed retains the aziridine stereochemistry in the case of cM-2,3-dimethylaziridine. 

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