Unsymmetrically Substituted Derivatives

Focants of substituents of symmetrically substituted derivatives of symmetrical amines are distinguished by primes or else the names of the complete substituted radicals are enclosed in parentheses. Unsymmetrically substituted derivatives are named similarly or as A-substituted products of a primary amine (after choosing the most senior of the radicals to be the parent amine). For example. 

Nitrobenzofuroxan (355) undergoes a rearrangement (recognizable as an isomerization in unsymmetrically substituted derivatives) which is an example of this general rearrangement (Scheme 45) (64AG(E)693) see Table 10. 

Tautomeric equilibrium in the symmetrical phenoxy-substituted derivative 136 (R = Ph, r = R = OPh) is fast at ambient temperature on the NMR time scale however, at —84°C the proton exchange becomes frozen and both annular tautomers 136a and 136b can be observed (Scheme 40). The similar exchange was also found for P-aryl-substituted 136 (R = Me, Ft, Ph R = R = Ph). In these cases, the equilibrium is very slow, even at ambient temperature, which was attributed to increased steric demands of four phenyl substituents. Unsymmetrically substituted azaphosphorinanes (R R ) provide even more interesting examples. These compounds (R = Ph R = Me, -Pr R = MeO, -PrO) were found to... 

Benzyl radicals and a- and 3- substituted derivatives also undergo unsymmetrical coupling through the aromatic ring (Section 2.5). The formation of the (i-o and a—p coupling products is reversible. Consequently, these materials are often only observed as transient intermediates. 

A question of regioselectivity arises when both the diene and alkene are unsymmetrically substituted and two different orientations are possible. Thus a 1-substituted diene with a mono substituted dienophile may form an ortho and a meta adduct. The same dienophile with a 2-substituted diene can yield a meta and a para product. Actually it has been observed that 1 sustituted dienes preferentially form ortho adducts whereas with 2-substituted derivatives para adducts are formed. 

Note that one significant difference between the above rules for radical reactions and the Woodward-Hoffmann W.-H) rules is that, whereas the W.-H rules for closed-shell reactions are not strictly speaking symmetry rules (they work for unsymmetrically substituted derivatives as well as for the symmetrical... 

The reactive zwitterions arising from the nucleophilic attack of imines 479 on the benzyne generated in situ from 2-(trimethylsilyl)phenyl triflate 478 proved to be an appropriate molecular scaffold for the capture of CO2 with sufficient electrophilicity to yield 2-aryl-3,l-benzoxazin+-ones 480 (Equation 53). Both substituents of the C=N bond affected the course of the reaction considerably the best yields were achieved by using imines with electron-rich or neutral aryl groups on the carbon, and benzyl or nonbranched chain alkyl substituents on the nitrogen atom. With substituted derivatives of 478, the unsymmetrically substituted arynes led to regioisomeric products <2006JA9308>. 

In the present discussion the terms symmetrically substituted and unsymmetrically substituted products refer to the nature of the parent hydrocarbons attached in a strictly linear fashion to the azo compound from which the azoxy compounds may be derived. For example, in this context the following structures are considered symmetrically substituted azoxy compounds ... 

A few current examples are shown below and include unsymmetrically substituted derivatives 14227, the cationic derivative 15228, the neutral derivative 16226 and the classic anionic derivative 17229 230, (tetrabenzoporphyrinato)zinc(II) , an intermediate structure between that of porphyrins and phthalocyanines, and have also been investigated in this respect. However, its quantum yield for singlet oxygen generation (0.023) in liposomes is much lower than that of Photofrin (0.19)177. 

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

Homonuclear correlation spectroscopy (COSY) experiments (see Chapter 9) substantiate the theoretical predictions, based on molecular orbital calculation, of the pattern of spin delocalization in the 3e orbitals of low-spin Fe(III) complexes of unsymmetrically substituted tetraphenylporphyrins [46]. Furthermore, the correlations observed show that this n electron spin density distribution is differently modified by the electronic properties of a mono-orf/io-substituted derivative, depending on the distribution of the electronic effect over both sets of pyrrole rings or only over the immediately adjacent pyrrole rings [46]. No NOESY cross peaks are detectable, consistently with expectations of small NOEs for relatively small molecules and effective paramagnetic relaxation [47]. 

A simplification can be effected, for unsymmetrically subsituted derivatives, by introducing a mean value of the a bonds population, namely (1/3) (2 + bi + b2), the results obtained for the V populations being quite similar to those of the symmetrically substituted derivatives... 

As with thiophene, 2,3-dibromobenzo[/ ]thiophene also exhibits a high regioselectivity in coupling reactions <2005T2245>. For example, Sonogashira coupling with /-butylacetylene leads exclusively to the 3-bromo derivative 90. 2,3-Unsymmetrically substituted derivatives of benzo[/ ]thiophene can be obtained by two successive crosscoupling reactions (Scheme 18). 

L-forms. In myo-inositol, the plane of symmetry is C-2/C-5 unsymmetrically substituted derivatives on C-1, C-3, C-4, and C-6 are chiral. Substitution at C-2 and/or C-5 gives a meio-product. fl/to-Inositol appears to have a plane of symmetry, but at room temperature it is actually a racemate formed of two enantiomeric conformers in rapid equilibrium. 

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