Carbon-bonded substituents Subject

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in entries 4—6. Single-crystal X-ray dilfiaction studies have unambiguously established that all the chlorine atoms of trans, cis, ira j-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal. Each chlorine in die molecule is bonded to an anomeric carbon and is subject to the anomeric effect. Equally striking is the observation that all the substituents of the tri-0-acetyl-/ -D-xylopyranosyl chloride shown in entry 5 are in the axial orientation in solution. Here, no special crystal packing forces can be invoked to rationalize the preferred conformation. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. 

Several epoxides hearing multiply-bonded substituents have Wu subjected to alcohol addition. Treatment of several vinyl-substituted ethylene oxides with sodium metboxide, for example, has been reported to yield alcohols corresponding to attack on the epoxide carbon iLtnnt furthest from the uiwaturated function. 6-l8S8- . > In the presence of a trace of mineral acid, however, methanol adds to the opposite terminal of the epoxide ring (Eq. 666),... 

Due the nature of the substituents, all the stable singlet carbenes exihibit some carbon-heteroatom multiple-bond character and for some time their carbene nature has been a subject of controversy. One has to keep in mind that apart from dialkyl-carbenes, all the transient singlet carbenes present similar electronic interactions. As early as 1956, Skell and Garner drew the transient dibromocarbene in its ylide form based on the overlap of the vacant p-orbital of carbon with the filled p orbitals of the bromine atoms (Scheme 8.31). 

In cases where more than one carbon-carbon double bond is present in the molecule, the possibility of selective cyclopropanation of one of them arises. Regiocontrol in intermole-cular cyclopropanation of substituted dienes has been the subject of much investigation and considerable differences can occur, depending on the structure of the substrate, catalyst and the carbene substituents. With a 1-substituted terminal diene such as 120, cyclopropanation, in general, occurs at the less-substituted double bond (equation 108)22 26,3, 16U62. In this case, the nature of the catalyst and of the carbenoid precursors are less important in determining the regioselectivity. 

Thus to permit cyclization, there must be at least one hydrogen a to the C=N bond. If there is only one, the product will be a 3,3-disubstituted-3H-indole. However, if both substituents at the hydrazone carbon have one or more a-hydrogens, product mixtures can result. Generally, it is expected that the more branched substituent is more likely to be involved in cyclization, so typically phenylhydrazones derived from methyl alkyl ketones give 2-methylindoles. However, the selectivity is subject to the reaction conditions and with certain reagents the selectivity can be reversed to favor the 2-alkylindole. 

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