Page 261 - Advanced Organic Chemistry Part B - Reactions & Synthesis

3.2.5. Sulfur Nucleophiles 233
Anions derived from thiols are strong nucleophiles and are easily alkylated by SECTION 3.2
halides. Introduction of
Functional Groups by
C H OH
2 5
+
–
CH S Na + ClCH CH OH CH 3 SCH 2 CH 2 OH Nucleophilic Substitution
2
3
2
at Saturated Carbon
Ref. 80
75–80%
Neutral sulfur compounds are also good nucleophiles, Sulfides and thioamides readily
form salts with methyl iodide, for example.
25°C
+ –
(CH ) S + CH I (CH ) S I
3 2
3 3
3
12–16 h Ref. 81
25°C
S + CH I + SCH 3
N 3 12 h N
CH 3 CH 3 Ref. 82
Even sulfoxides, in which nucleophilicity is decreased by the additional oxygen, can be
alkylated by methyl iodide. These sulfoxonium salts have useful synthetic applications
as discussed in Section 2.5.1.
25°C +
) S O +CH I (CH ) S O I –
(CH 3 2 3 3 2 Ref. 83
72 h
3.2.6. Phosphorus Nucleophiles
Both neutral and anionic phosphorus compounds are good nucleophiles toward
alkyl halides. We encountered examples of these reactions in Chapter 2 in connection
with the preparation of the valuable phosphorane and phosphonate intermediates used
for Wittig reactions.
room temp +
Ph P+CH Br Ph PCH Br – Ref. 84
3
3
3
3
2 days
O
) CHO] P + CH I [(CH ) CHO] PCH ) CHI Ref. 85
[(CH 3 2 3 3 3 2 2 3 +(CH 3 2
The reaction with phosphite esters is known as the Michaelis-Arbuzov reaction and
proceeds through an unstable trialkoxyphopsphonium intermediate. The second stage
is another example of the great tendency of alkoxyphosphonium ions to react with
nucleophiles to break the O−C bond, resulting in formation of a phosphoryl P−O
bond.
O
+
(R′O) P + XCH R (R′O) P CH R (R′O) PCH R + R′X
2
2
3
2
3
2
X –
80
W. Windus and P. R. Shildneck, Org. Synth., II, 345 (1943).
81 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 87, 1353 (1965).
82
R. Gompper and W. Elser, Org. Synth., V, 780 (1973).
83 R. Kuhn and H. Trischmann, Justus Liebigs Ann. Chem., 611, 117 (1958).
84 G. Wittig and U. Schoellkopf, Org. Synth., V, 751 (1973).
85
A. H. Ford-Moore and B. J. Perry, Org. Synth., IV, 325 (1963).