Union intermolecular

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

It is worth pointing out that the stereochemistry of intermediate 147 at C-9 and C-10 is inconsequential since both positions will eventually bear trigonal carbonyl groups in the final product. The synthetic problem is thus significantly simplified by virtue of the fact that any or all C9-C10 diol stereoisomers could be utilized. A particularly attractive means for the construction of the C9-C10 bond and the requisite C8-C10 functionality in 147 is revealed by the disconnection shown in Scheme 41. It was anticipated that the venerable intermolecular aldol reaction could be relied upon to accomplish the union of aldehyde 150 and methyl glycolate (151) through a bond between carbons 9 and 10. 

The precise mechanism of these intermolecular reactions is not known. Transient disproportionation processes, although well documented in less acidic media (see below and Section V.A.l), seem unlikely if alkyl cations alone are involved. Two possible explanations for the observed results may be considered. Small amounts of polymeric impurities may be present in the reaction mixture which could serve as a hydride source, catalyzing the intermolecular reaction as indicated in Eq. (16)4°). Alternatively, the intermolecular reactions may result from inefficient mixing during reaction initiation. In this case, unionized alcohols would serve as the hydride source. This latter alternative is consistent with the observation 4°1 that the deuterium in the 1-adamantanol obtained from the rearrangement of 38 is distributed between bridgehead and methylene positions. Unless more than one re-... 

Intermolecular condensation. A condensation reaction which occurs between separate molecules, resulting in their union (hence a process of accretion to form polymers). See example under Condensation. 

Static and dynamic light scattering studies by Milhem have shown that G4 PAMAM dendrimers do not exhibit intermolecular aggregation in aqueous solution at concentrations up to 7%w/w at pH 10.5, or even when fully unionized at pH 14. 

Intermolecular union of two aromatic nuclei can be effected by means of aluminum chloride in the same way as in the pyrochemical reactions discussed above except that presence of a catalyst permits reaction at lower temperatures. 

The extracted alkoxide ion may be solvated by unionized alcohol molecules via the intermolecular hydrogen bonding. 

Figure 1.4 A generalised 3DSEARCH query containing three substructures (1-3) with four specified connections. The substructures can be of any type and can be specified in the usual way (atom types, bond types, etc.). The connections are defined between specified atoms in each substructure and can be constrained using a range of criteria (intra- or intermolecular, distance, angle, torsion). Reproduced from [32] by permission of the International Union of Crystallography...

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