Fragmentation stereochemistry

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. 

After the stmcture and absolute stereochemistry of cleavamine (111), C22H24N2, was estabUshed, its synthesis was shortly completed and impetus to unravel the stmcture of the dimeric bases (22) was bolstered (77). Again, the fragment, now only slightly modified from that originally present in secologanin (102), is readily seen in catharanthine (107). 

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. 

There are also examples of electrocyclic processes involving anionic species. Since the pentadienyl anion is a six-7c-electron system, thermal cyclization to a cyclopentenyl anion should be disrotatory. Examples of this electrocyclic reaction are rare. NMR studies of pentadienyl anions indicate that they are stable and do not tend to cyclize. Cyclooctadienyllithium provides an example where cyclization of a pentadienyl anion fragment does occur, with the first-order rate constant being 8.7 x 10 min . The stereochemistry of the ring closure is consistent with the expected disrotatory nature of the reaction. 

The stereochemistry at C-20 does not affect the reaction. However, the 16j5-mesyloxy analogs give poor yields of fragmentation product, as would be predicted from the syn periplanar arrangement of the bonds involved. 

Pieces of various routes to moxalactam have been published from which the following may be assembled as one of the plausible pathways. The benzhydrol ester of 6-aminopenici 11 anic acid ( ) is -chlorinated and treated with base whereupon the intermediate sulfenyl chloride fragments to ). Next, displacement with propargyl alcohol in the presence of zinc chloride gives predominantly the stereochemistry represented by dia-stereoisomer The side chain is protected as the phenyl-... 

O-Isopropylidene derivatives of carbohydrates form structural isomers from carbohydrates which themselves are epimers. Since structural isomers often fragment differently whereas epimers do not, mass spectra of these derivatives may permit interpretation in terms of stereochemistry. Although molecular-ion peaks are not observed, the molecular weight can be determined readily from a relatively intense M-CH/ peak, resulting from loss of a methyl radical from a 1, 3-dioxolane ring (12). 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

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 three fragments were then coupled. The C(16)—C(17) bond was established by addition of the lithium enolate of the aryl ester in the C(9)—C(16) fragment with the aldehyde group of the C(17)-C(24) fragment. The stereochemistry is consistent with the cyclic aldol addition TS. The adduct was immediately reduced to the diol 14 by LiAlH4. 

We have designed PBUILD, a new CHEMLAB module, for easy construction of random copolymers. A library of monomers has been developed from which the chemists can select a particular sequence to generate a polymeric model. PBUILD takes care of all the atom numbering, three dimensional coordinates, and knows about stereochemistry (tacticity) as well as positional isomerism (head to tail versus head to head attachment). The result is a model of the selected polymer (or more likely a polymer fragment) in an all trans conformation, inserted into the CHEMLAB molecular workspace in literally a few minutes. 

What of the other suggested products in Fig. 29 The RG33-type fragmentation leading to 20 is still formally permitted by EROS. However, orbital symmetry constraints suggest that such a reaction would not occur in practice. As yet, EROS pays no heed to this type of orbital overlap consideration, which depends on knowledge of stereochemistry and conformation. 

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