Page 663 - Advanced Organic Chemistry Part B - Reactions & Synthesis

638 O O
–30°C
CH (CH ) MgBr + CH CH CH CCl CH (CH ) C(CH ) CH
CHAPTER 7 3 2 5 3 2 2 3 2 5 2 2 3
92%
Organometallic
Compounds of Group I
and II Metals
2-Pyridinethiolate esters, which are easily prepared from acyl chlorides, also react
with Grignard reagents to give ketones (see Entry 6 in Scheme 7.3). 92 N-Methoxy-
N-methylamides are also converted to ketones by Grignard reagents (see Entries 17
and 18).
Aldehydes can be obtained by reaction of Grignard reagents with triethyl ortho-
formate. The addition step is preceded by elimination of one of the alkoxy groups to
generate an electrophilic oxonium ion. The elimination is promoted by the magnesium
ion acting as a Lewis acid. 93 The acetals formed by the addition are stable to the
reaction conditions, but are hydrolyzed to aldehydes by aqueous acid.
R
Mg X
H O H
C 2 5 OC 2 5
H
OC 2 5 RMgX H +
H C OC 2 5 HC + RCH RCH O
H
OC H H O
2
2 5
C H O OC H
2 5
2 5
+ C H OMgR + X –
2 5
Aldehydes can also be obtained from Grignard reagents by reaction with formamides,
such as N-formylpiperidine. In this case, the initial adducts are stable and the aldehyde
is not formed until hydrolysis during workup.
O
H O
2
PhCH CH MgCl + HC N PhCH 2 CH CH O
2
2
2
66 –76%
Ref. 94
The addition of Grignard reagents to aldehydes, ketones, and esters is the basis
for the synthesis of a wide variety of alcohols, and several examples are given in
Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with
addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained
from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can
be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols
(Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries
12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-
thiol esters (Entry 16), N-methoxy-N-methyl carboxamides (Entries 17 and 18), or
anhydrides (Entry 19). Carboxylic acids are available by reaction with CO (Entries
2
20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures
that involve formation and dehydration of alcohols provide routes to certain alkenes
(Entries 24 and 25).

92
T. Mukaiyama, M. Araki, and H. Takei, J. Am. Chem. Soc., 95, 4763 (1973); M. Araki, S. Sakata,
H. Takai, and T. Mukaiyama, Bull. Chem. Soc. Jpn., 47, 1777 (1974).
93 E. L. Eliel and F. W. Nader, J. Am. Chem. Soc., 92, 584 (1970).
94
G. A. Olah and M. Arvanaghi, Org. Synth., 64, 114 (1985); G. A. Olah, G. K. S. Prakash, and
M. Arvanaghi, Synthesis, 228 (1984).