Page 344 - Advanced Organic Chemistry Part B - Reactions & Synthesis

316 Related O-TBS and O-benzyl ethers cyclize with loss of the ether substituent.

CHAPTER 4 I
I 2
Electrophilic Additions CH CH CH = CHCH CH OR
2
2
3
2
to Carbon-Carbon
NaHCO 3
Multiple Bonds O CH CH 3
2
R = TBS, benzyl Ref. 87
Other nucleophilic functional groups can participate in iodocyclization. Amides
usually react at oxygen, generating imino lactones that are hydrolyzed to lactones. 88
O
I , H O R N + O R H O O R
2
2
2
R 2 NCCH 2 CH 2 CH CHR 2 O
DME I I
Ref. 89
Use of a chiral amide can promote enantioselective cyclization. 90
OCH Ph
CH 2 2 O CH 2 I
O I O
N 2
CH 2
THF, H O
2
CH 3 CH 3 90:10 trans:cis
66% e.e.
CH 2 OCH Ph
2
The TS preference is influenced by avoidance of A 1 3 strain between the -methyl
group and the piperidine ring.
PhCH O CH 3 PhCH O
2
2
PhCH 2 O O I + PhCH O O +
2
N N I
CH 3
preferred pro-trans TS pro-cis TS
Lactams can be obtained by cyclization of O,N-trimethylsilyl imidates. 91

O ICH 2 H
TMS – O SCF 3 1) I 2 N
3
CH 2 CHCH CH CNH 2 CH 2 CHCH CH C NTMS O
2
2
2
2
Et N 2) Na SO 3
2
3
OTMS 86%
As compared with amides, where oxygen is the most nucleophilic atom, the silyl
imidates are more nucleophilic at nitrogen.
Examples of halolactonization and related halocyclizations can be found in
Scheme 4.4. The first entry, which involves NBS as the electrophile, demonstrates the
anti stereospecificity of the reaction, as well as the preference for five-membered rings.
87 S. P. Bew, J. M. Barks, D. W. Knight, and R. J. Middleton, Tetrahedron Lett., 41, 4447 (2000).
88 S. Robin and G. Rousseau, Tetrahedron, 54, 13681 (1998).
89
Y. Tamaru, M. Mizutani, Y. Furukawa, S. Kawamura, Z. Yoshida, K. Yanagi, and M. Minobe, J. Am.
Chem. Soc., 106, 1079 (1984).
90 S. Najdi, D. Reichlin, and M. J. Kurth, J. Org. Chem., 55, 6241 (1990).
91
S. Knapp, K. E. Rodriquez, A. T. Levorse, and R. M. Ornat, Tetrahedron Lett., 26, 1803 (1985).