Page 62 - Advanced Organic Chemistry Part B - Reactions & Synthesis

34 CH 3
+
–
2 LDA CH 3 O Li 1) CH 3 (CH ) Br
2 3
(CH ) CHCO H CH (CH ) CCO H
CHAPTER 1 3 2 2 + 3 2 3 2
–
O Li + 2) H
CH 3 CH
Alkylation of Enolates 3
and Other Carbon 80%
Nucleophiles
Nitriles can also be converted to anions and alkylated. Acetonitrile pK DMSO = 31 3
can be deprotonated, provided a strong nonnucleophilic base such as LDA is used.
1)
LDA O
CH C N LiCH C N (CH 3 3 2 2 2 N
) SiOCH CH CH C
3
2
THF 2) (CH 3 3
) SiCl
78%
Ref. 77
Phenylacetonitrile pK DMSO = 21 9 is considerably more acidic than acetonitrile.
Dialkylation has been used in the synthesis of meperidine, an analgesic substance. 78
NaNH steps
CH CN + CH N(CH CH Cl) 2 2 NCH 3 NCH 3
3
2
2
2
CN
CO CH CH 3
2
2
meperidine
We will see in Section 1.2.6 that the enolates of imides are very useful in synthesis.
Particularly important are the enolates of chiral N-acyloxazolidinones.
Scheme 1.6 gives some examples of alkylation of esters, amides, and nitriles.
Entries 1 and 2 are representative ester alkylations involving low-temperature
Scheme 1.6. Alkylation of Esters, Amides, and Nitriles
1 a 1) LDA, THF, –70°C CO CH 3
2
CO CH 3
2
2 6
2) CH (CH 2 ) 3 I, HMPA, 25°C (CH ) CH 3
3
~90%
2 b
+
1) NCH(CH ) Li , –78°C (CH ) CHCO C H
CH 3 (CH 2 ) 4 CO 2 C 2 H 5 3 2 CH 3 2 3 2 2 5
CH CH CH CH
2) CH CH CH CH Br 2 2 2 3
2
2
2
3
75%
3 c H H
CH 3 O 1) LDA, DME CH 3 O
O O
) CH
2) CH 2 CH(CH ) Br (CH 2 3 CH 2
2 3
CH 3 3) LDA, DME H 3 C CH 3 86%
4) CH 3 I
4 d O O
CH 3
H 1) LDA H
O O
H 2) CH 3 I, HMPA H
82%
(Continued)
77 S. Murata and I. Matsuda, Synthesis, 221 (1978).
78
O. Eisleb, Ber., 74, 1433 (1941); cited in H. Kagi and K. Miescher, Helv. Chim. Acta, 32, 2489 (1949).