Page 900 - Advanced Organic Chemistry Part B - Reactions & Synthesis

876 The cyclization of the -ketoester 6 can be effected by Mg(ClO , Yb(OTf) ,
3
4 2
Cu(OTf) , or Sc(OTf) . 45 The reaction exhibits a 20:1 preference for formation of the
2
3
CHAPTER 10
trans-2-(1-methylpropenyl) isomer. The reaction can be conducted with greater than
Reactions Involving 90% e.e. using Cu(OTf) or Sc(OTf) with the t-Bu-BOX ligand.
Carbocations, Carbenes, 2 3
and Radicals as Reactive
Intermediates OH OH
O C H CO 2 2 5
C H
CH 3 Lewis acid CO 2 2 5 +
C H
CO 2 2 5 CH 3 CH 3
CH 3 6 CH
CH 2 2
20:1
As an example of a thermal reaction, 7 cyclizes at 180 C. The reaction is stereoselective

and the two stereoisomers can be formed from competing cyclic TSs. 46
CH 3
CH 2
OR 1
OR 1 HO
H 2
CH 3 O CO R 2 R O 2 C CH 3 preferred by 5:1
O 2
1
R O CO 2 R 2
OR 1 CH 2
CH 3 OR 1
7 CO 2 R 2 HO
O 2
H CH 3 R O 2 C CH 3
Carbonyl-ene reactions can be carried out in combination with other kinds of
reactions. Mixed acetate acetals of , -enols, which can be prepared from the corre-
sponding acetate esters, undergo cyclization with nucleophilic capture. When SnBr
4
is used for cyclization, the 4-substituent is bromine, whereas BF in acetic acid gives
3
acetates. 47
O O CCH 3 X
2
1) DiBAlH Lewis R 1
O CH 3 O CH 3 acid
R' 2) Ac O, R'
R 2 R O CH
pyridine R 3
X Br, O CCH 3
2
The reaction stereochemistry is consistent with a cyclic TS.

O CCH 3 Br
2
+
O CH 3 + R 1 R 1 R 1
R' R O CH 3 R O CH 3 R O CH 3
R
A tandem combination initiated by a Mukaiyama reaction generates an oxonium ion
that cyclizes to give a tetrahydropyran rings. 48

45
D. Yang, M. Yang, and N.-Y. Zhu, Org. Lett., 5, 3749 (2003).
46
H. Helmboldt, J. Rehbein, and M. Hiersemann, Tetrahedron Lett., 45, 289 (2004).
47 J. J. Jaber, K. Mitsui, and S. D. Rychnovsky, J. Org. Chem., 66, 4679 (2001).
48
B. Patterson and S. D. Rychnovsky, Synlett, 543 (2004).