Differentiation substitution

Bicyclo[3.3.1]nonan-9-one is another ketone that exhibits interesting stereoselectivity. Reduction by hydride donors is preferentially syn to electron-attracting substituents at C-5 (X = EWG in the structure shown below) and anti to electron-releasing substituents (X = ERG below). These effects are observed even for differentially substituted phenyl... 

Another limitation of the traditional Cu-mediated cyclooligomerization reaction is generation of differentially substituted PDMs. In the above case, the substitution pattern in the starting o-diethynylbenzene must be maintained on each and every benzene moiety in the oligomeric mixture of PDMs that is produced. Thus, it is impossible to prepare less symmetric systems like 100 via this route. With the intramolecular synthetic approach, however, it should be possi-... 

Combinatorial approaches can be applied to the synthesis of any type of molecule that can be built up from a sequence of individual components, for example, in reactions forming heterocyclic rings.63 The equations below represent an approach to preparing differentially substituted indoles. 

A 2-step route to oxygenated bicyclo[n.3.0]alkanes via bicyclic 4-pyrones such as 133 has been reported (equation 2)62. Irradiation in hydroxy lie solvents caused ring contraction to the zwitterion, followed by solvent incorporation to give fused bicyclic cyclopentenone 134. Good regioselectivity in favor of solvent capture at the more substituted oxyallyl terminus was seen in differentially substituted examples, presumably due to increased... 

The absolute stereochemistry for 150 (entries 2 and 3) was determined by hydrolysis and conversion to known compounds. Assuming a tetrahedral or cis octahedral geometry for the magnesium [110], the product stereochemistry is consistent with si face radical addition to an s-cis conformer of the substrate. This is the same sense of selectivity as that obtained with oxazo-lidinone crotonates or cinnamates suggesting that the rotamer geometry of the differentially substituted enoates is the same. The need for stoichiometric amount of the chiral Lewis acid to obtain high selectivity with 148 in contrast to successful catalytic reactions with crotonates is most likely a reflection of the additional donor atom present in the substrate. 

Table I. Means and Standard Deviations of the Data for 23 Differentially Substituted Pyridazinones Before and After Analysis by Ward s Method.

Table II. Experimentally Determined 18 2/18 3 Ratios of Differentially Substituted 4-chloro-5-dimethylamino-pyridazin-3-ones and the Corresponding and o Values.

On the other hand, differential substitution adj acent to equivalently substituted a positions does not afford a good regiochemical control (compare 103 and 104, equation 35) . 

Brummond [28] was the first to illustrate that cross-conjugated trienes could be obtained via an allenic Alder-ene reaction catalyzed by [Rh(CO)2Cl]2 (Eq. 14). Selective formation of the cross-conjugated triene was enabled by a selective cycloisomerization reaction occurring with the distal double bond of the aUene. Typically directing groups on the allene, differential substitution of the aUene termini, or intramolecularization are required for constitutional group selectivity. However, rhodium(f), unlike other transition metals examined, facihtated selective cyclization with the distal double bond of the allene in nearly aU the cases examined. 

Gassner, N. C. and Matthews, B. W. (1999). Use of differentially substituted selenomethionine proteins in X-ray structure determination. Acta Crystallogr. D 55, 1967-1970. 

Many reagents known for the direct conversion of alcohols into halides have been used to achieve site-selective nucleophilic substitution in polyhydroxy compounds [44-46,62]. In some cases, it is possible to effect selective displacements of primary alcohols in the presence of secondary ones, and to achieve differential substitutions of secondary alcohols in unprotected sugars [44,45,64,65] (Scheme 4). 

Several related methods for the preparation of differentially substituted 5-thio-2,3-trisubstituted furans were developed, which involved the formation of a thionium ion and the cyclization of this reactive intermediate into the tethered carbonyl group <02JOC1595>. 

This is only a guideline, and in many cases it is not easy to be sure. Instead of concerning ourselves with these uncertainties, we shall move on to some differentially substituted cyclohexanes for which it is absolutely certain which conformer is preferred. 

In the case of 3.25 and the difunctionalized derivative 3.30, Richert, et al. have performed various functional group interconversion. This has afforded a number of differentially substituted porphycenes." For instance, it was found that when the porphycene tetraether 3.25 was treated with 0.74 equivalents of BBry, the mono-refunctionalized derivative 3.96 could be isolated in 18% yield (Scheme 3.1.18). However, the selectivity in this reaction was low. In fact, it afforded, in addition to 3.96, a 50-60% return of educt 3.25 along with the three possible isomeric dialcohols 3.97-3.99 (10-12% combined yield) and the trialcohol 3.100 in 4% yield. Fortunately, with the exception of the dialcohol isomers 3.97-3.99, these products could be readily separated by standard chromatographic means. These types of isomer problems were not encountered in the case of diether 3.30. Here, treatment... 

The fugacity of the leaving groups at allylic positions is demonstrated to be in the order —OPO(OEt)2 > —OAc > —OH and —Cl > —OAc > - H. Therefore, chemoselective stepwise substitution of differentially substituted bifunctional allylic substrates is possible as depicted in Scheme 51 In the... 

In principle, either of the C(sp2) atoms in an alkene may form a new bond to an electrophile. If the alkene is differentially substituted, though, one is usually more nucleophilic than the other. 

An indicator variable I was added to the above equation to differentiate substituted 2-phenethylamine derivatives sueh as amphetamine from unsubstituted 2-phenethyl-amine compounds. The eorrelation eoeffi-cient (r) for the equation was high (r = 0.965), whereas s, the standard deviation. 

Moody, C.J., and Miller, D.J., Reactivity of differentially substituted i>w(diazo) esters in rhodium(ll) mediated O-H insertion reactions. Tetrahedron, 54, 2257, 1998. 

UV-visible spectra have been used in studies of the amino-imino tautomerism of differentially substituted 2-aminothiazoles and 2-amlnobenzothiazoles <92JHC1461,94JCS(P2)615>. The spectra were recorded in different solvents and in the presence of variable amounts of salts in order to change medium polarity. 

Hilt took a slightly different approach toward the functionalization of cyclohexadienes [88, 89], He reasoned that subsequent DDQ oxidation of the insertion products would provide facile access to substituted benzene derivatives 101 that would be difficult to obtain by traditional means (Scheme 21). These sequential reactions typically took place in moderate to good yields with Rh2(OAc)4 (25a) or Cu(hfacac) (hfacac=hexafluoroacetylacetonate) as the catalyst, thus generating racemic products. Notably, when differentially substituted 1,4-cyclohexa-dienes (100, R2 =H) were used as the substrates, the insertion event occurred exclusively at the less sterically hindered site. 

---