Page 383 - Advanced Organic Chemistry Part B - Reactions & Synthesis

This methodology has been used to create chiral centers in saturated hydrocarbon 355
chains such as those found in vitamin E, vitamin K, and phytol. 225
SECTION 4.6
85% CH
1) (CH ) Al CH 3 MgBr 3 Hydroalumination,
3 3
CH(CH ) cat K CH(CH ) Carboalumination,
CH 2 3 2 CH(CH ) 3 2 Hydrozirconation,
2) I ICH 2 3 2 Li 2 CuCl
2 4 and Related Reactions
1) (CH ) Al
3 3
cat K
2) O 2
CH CH
3 3
HO CH(CH )
3 2
76%. 74% e.e.
By converting the primary alcohol group to an alkene by oxidation and a Wittig
reaction, the reaction can be carried out in iterative fashion to introduce several methyl
groups. 226
CH
3 CH
5 mol % cat K CH 3 1) oxdn. 3
CH 2 OH + (C H ) Al 1 eq IBAO C H 2) Ph P CH C H 5
2
5 3
2
2
5
OH 3 2 CH 2
1) (CH ) Al, MAO
3 3
5 mol % cat K
2) O 2
CH
CH 3 3
C H 5 OH
2
At this point in time carboalumination of alkynes has been more widely applied
in synthesis. The most frequently used catalyst is Cp ZrCl . It is believed that a
2 2
bimetallic species is formed. 227
Cl
ZrCl + Al
(Cp) 2 2 R 3 (CH ) Al Zr(Cp) CH 3
2
3 2
Cl
Cl R R
(CH ) Al Zr(Cp) CH 3 + RC CR
2
3 2
Cl (CH ) Al CH 3
3 2
Small amounts of water accelerate carboalumination of alkynes. 228 This acceleration
may be the result of formation of aluminoxanes.
CH (CH )
1) 0.2 eq (Cp) ZrCl 2 3 2 3 CH 2 CH (CH )
3
2 3
2
) Al
CH (CH ) C CH + (CH 3 3 + CH 3
3
2 3
H O CH
2
2) H + 3
97:3
1) 0.2 eq (Cp) ZrCl 2 HOCH CH 2
2
2
CH C CH + ) Al
HOCH 2 2 (CH 3 3 I
H O
2
CH
2) I 2 3
225
S. Huo and E. Negishi, Org. Lett., 3, 3253 (2001).
226
E. Negishi, Z. Tan, B. Liang, and T. Novak, Proc. Natl. Acad. Sci. USA, 101, 5782 (2004);
M. Magnin-Lachaux, Z. Tan, B. Liang, and E. Negishi, Org. Lett., 6, 1425 (2004).
227 E. Negishi and D. Y. Kondakov, Chem. Soc. Rev., 25, 417 (1996).
228
P. Wipf and S. Lim, Angew. Chem. Int. Ed. Engl., 32, 1068 (1993).