Page 333 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Table 4.2. Other Sources of Electrophilic Halogen 305
Reagents Synthetic applications a SECTION 4.1
A. Chlorinating agents Electrophilic Addition to
Alkenes
Sodium hypochlorite solution Formation of chlorohydrins from alkenes
N-Chlorosuccinimide Chlorination with solvent participation and cyclization
Chloramine-T b Formation of chlorohydrins in acidic aqueous solution.
B. Brominating agents
Pyridinium hydrotribromide (pyidinium Mild and selective substitute for bromine
hydrobromide perbromide)
Dioxane bromine complex Same as for pyridinium hydrotribromide
N-Bromosuccinimide Used in place of bromine when low bromide
concentration is required.
2,4,4,6-Tetrabromocyclohexadienone c Selective bromination of alkenes and carbonyl
compounds
Quaternary ammonium tribromides d Similar to pyridinium hydrotribromide
C. Iodinating agents
bis-(Pyridinium)iodonium e Selective iodination and iodocyclization.
tetrafluoroborate
a. For specific examples, consult M. Fieser and L. F. Fieser, Reagents for Organic Synthesis, John Wiley & Sons, New
York.
b. B. Damin, J. Garapon, and B. Sillion, Synthesis, 362 (1981).
c. F. Calo, F. Ciminale, L. Lopez, and P. E. Todesco, J. Chem. Soc., C, 3652 (1971) ;Y. Kitahara, T. Kato, and I. Ichinose,
Chem. Lett., 283 (1976)
d. S. Kaigaeshi and T. Kakinami, Ind. Chem. Libr., 7, 29 (1985); G. Bellucci, C. Chiappe, and F. Marioni, J. Am. Chem.
Soc., 109, 515 (1987).
e. J. Barluenga, J. M. Gonzalez, M. A. Garcia-Martin, P. J. Campos, and G. Asensio, J. Org. Chem., 58, 2058 (1993).

Electrophilic iodine reagents are extensively employed in iodocyclization (see
Section 4.2.1). Several salts of pyridine complexes with I + such as bis-
(pyridinium)iodonium tetrafluoroborate and bis-(collidine)iodonium hexafluorophos-
phate have proven especially effective. 53

4.1.5. Addition of Other Electrophilic Reagents

Many other halogen-containing compounds react with alkenes to give addition
products by mechanisms similar to halogenation. A complex is generated and the
halogen is transferred to the alkene to generate a bridged cationic intermediate. This
may be a symmetrical halonium ion or an unsymmetrically bridged species, depending
on the ability of the reacting carbon atoms to accommodate positive charge. The
direction of opening of the bridged intermediate is usually governed by electronic
factors. That is, the addition is completed by attack of the nucleophile at the more
positive carbon atom of the bridged intermediate. The regiochemistry of addition
therefore follows Markovnikov’s rule. The stereochemistry of addition is usually anti,
because of the involvement of a bridged halonium intermediate. 54 Several reagents of
this type are listed in Entries 1 to 6 of Scheme 4.2. The nucleophilic anions include
isocyanate, azide, thiocyanate, and nitrate.
Entries 7 to 9 involve other reagents that react by similar mechanisms. In the
+
case of thiocyanogen chloride and thiocyanogen, the formal electrophile is NCS .
The presumed intermediate is a cyanothiairanium ion. The thiocyanate anion is an
53 Y. Brunel and G. Rousseau, J. Org. Chem., 61, 5793 (1996).
54
A. Hassner and C. Heathcock, J. Org. Chem., 30, 1748 (1965).