Page 247 - Advanced Organic Chemistry Part B - Reactions & Synthesis

amount of t-butyl bromide is also formed. 11 The extent of rearrangement increases 219
with increasing chain length and branching.
SECTION 3.1
PBr 3 Conversion of Alcohols
CH CH CHCH CH 3 CH CH CHCH CH 3 + CH CH CH CHCH 3
2
3
2
2
3
2
2
3
2
ether to Alkylating Agents
OH Br Br
85–90% 10–15%
Ref. 12
PBr 3
(CH ) CCH OH (CH ) CCH Br + (CH ) CCH CH + CH CHCH(CH )
3 3
3 3
2
2
2
3 2
3 2
3
3
quinoline
Br Br
63% 26% 11%
Ref. 13
Owing to the acidic conditions, these methods are limited to acid-stable molecules.
Milder reagents are necessary for many functionally substituted alcohols. A very
general and important method for activating alcohols toward nucleophiles is by
converting them to alkoxyphosphonium ions. 14 The trivalent phosphorus reagents are
activated by reaction with a halogen or related electrophile, and the alkoxyphos-
phonium ions are very reactive toward nucleophilic attack, with the driving force for
substitution being formation of the strong phosphoryl bond.
E
+
R′ P E Y R′ 3 P R′ P + E + Y –
3
3
Y
P + R′ P +
R′ 3 E + ROH 3 OR + HE
R′ P + OR + Nu – R′ P O + R Nu
3
3
+
A variety of reagents can function as the electrophile E in the general mechanism. The
most useful synthetic procedures for preparation of halides are based on the halogens,
positive halogens sources, and diethyl azodicarboxylate. A 1:1 adduct formed from
15
triphenylphosphine and bromine converts alcohols to bromides. The alcohol displaces
bromide ion from the pentavalent adduct, giving an alkoxyphosphonium intermediate.
The phosphonium ion intermediate then undergoes nucleophilic attack by bromide ion,
forming triphenylphosphine oxide.
PPh 3 + Br 2 Br PPh 3
2
–
+
Br PPh 3 + ROH ROP Ph Br + HBr
3
2
+
Br – + ROP Ph 3 RBr + Ph P O
3
The alkoxy phosphonium intermediate is formed by a reaction that does not break the
C−O bond and the second step proceeds by back-side displacement on carbon, so the
stereochemistry of the overall process is inversion.
11 D. G. Goodwin and H. R. Hudson, J. Chem. Soc. B, 1333 (1968); E. J. Coulson, W. Gerrard, and
H. R. Hudson, J. Chem. Soc., 2364 (1965).
12
J. Cason and J. S. Correia, J. Org. Chem., 26, 3645 (1961).
13 H. R. Hudson, J. Chem. Soc., 664 (1968).
14 B. P. Castro, Org. React., 29, 1 (1983).
15
G. A. Wiley, R. L. Hershkowitz, B. M. Rein, and B. C. Chung, J. Am. Chem. Soc., 86, 964 (1964).