Page 103 - Advanced Organic Chemistry Part B - Reactions & Synthesis

such as the N-acyloxazolidinones that serve as chiral auxiliaries (see Section 2.1.3.4). 75
Mixed aldehyde-aldehyde additions have been carried out using TiCl and
4
TMEDA. The reaction gives syn adducts, presumably through a cyclic TS. Treatment SECTION 2.1
Aldol Addition and
of the syn adducts with 1 mol % Ti O-i-Pr leads to equilibration to the more stable Condensation Reactions
4
anti isomer. 23
TiCl 4 OH OH
PhCH O + CH CH CH O Ti(O-i-Pr) 4 CH O
3
2
TMEDA Ph CH O 1 mol % Ph
–30 °C
CH
CH 3 3
69% >98:2 syn:anti 7:93 syn:anti
The equilibration in this case is believed to involve oxidation-reduction at the alcohol
center, rather than reversal of the addition. (See Section 5.3.2 for a discussion of
Ti O-i-Pr as an oxidation-reduction catalyst.)
4
Ketone-aldehyde additions have been effected using TiCl in toluene. 24 These
4
reactions exhibit the same stereoselectivity trends as other titanium-mediated additions.
With unsymmetrical ketones, this procedure gives the product from the more-
substituted enolate. 25

O O OH
TiCl
CH C(CH ) CH 3 + PhCH O 4 CH Ph
2 4
3
toluene 3 87%
(CH ) CH 3
2 3
72:28 syn:anti
Titanium enolates can also be used under conditions in which the titanium exists
as an “ate” species. Crossed aldehyde-aldehyde additions have been accomplished
starting with trimethylsilyl enol ethers, which are converted to lithium enolates and
26
then to “ate” species by addition of Ti O-n-Bu . These conditions show only modest
4
stereoselectivity.
OH
OTMS 1) CH Li RCH O CH O
3
C H R
8 17
H
2) Ti(O-n-Bu) 4 C 8 17
Silyl enol ether R syn:anti
Z C 2 H 5 28:72
Z CH 3 2 CH 20:80
Z CH 3 3 C 10:90
Z Ph 54:46
E CH 3 2 CH 47:53
E CH 3 3 C 28:72

Titanium “ate” species have also been used to add aldehyde enolates to ketones.
This reaction is inherently difficult because of the greater reactivity of aldehyde

23
R. Mahrwald, B. Costisella, and B. Gundogan, Synthesis, 262 (1998).
24 R. Mahrwald, Chem. Ber., 128, 919 (1995).
25 R. Mahrwald and B. Gundogan, J. Am. Chem. Soc., 120, 413 (1998).
26
K. Yachi, H. Shinokubo, and K. Oshima, J. Am. Chem. Soc., 121, 9465 (1999).