Page 998 - Advanced Organic Chemistry Part B - Reactions & Synthesis

974 OH
NHOCH Ph
2
Bu SnH
CHAPTER 10 O CH(CH 2 3 2 NOCH 2 Ph 3
) NCH CH
Reactions Involving N
Carbocations, Carbenes, CO -t-C H
2
4 9
and Radicals as Reactive CO -t-C H
Intermediates 2 4 9
50% 1:2.6 cis.trans
Ref. 342
The reactivity of oxime ethers as radical acceptors is enhanced by Lewis acids, BF 3
being the most effective. 343
1) RI, Bu SnH
3
2) Et B
3
C H CH NOCH 2 Ph C H CHNHOCH Ph
2
2 5
2 5
3) BF 3
R = alkyl R
Addition to oxime ethers of glyoxylic acid generates N-benzyloxyamino acids. These
reactions have been done in both organic solvents 344 and aqueous mixtures. 345 The
reactions can be done with or without Bu SnH as a chain carrier.
3
1) RI, (Bu 3 SnH)
HO 2 CCH NOCH Ph + RI HO 2 CCHNHOCH Ph
2
2
2) Et 3 B
R
Scheme 10.18 gives some additional examples of cyclization reactions involving
radical intermediates. Section A pertains to reactions of alkyl halides. Entry 1 is an early
example of the application of a radical cyclization and was used in the synthesis of the
terpenes sativene and copacamphene. Entry 2 is an example of the use of the -bromo-
-ethoxyethyl group in radical cyclization. Ring strain effects dictate the formation of
the cis-fused five-membered ring, and the stereochemistry of the decalin ring junction
is then controlled by the shape of the tricyclic radical intermediate, resulting in good
stereochemical control. Entry 3 involves addition of an alkenyl radical. Entry 4 involves
generation of a vinyl radical that undergoes stereoequilibration faster than cyclization.
The 6-endo mode of cylization is favored by both steric and radical stabilization
effects. Entry 5 is an 5-exo cyclization. Several similar reactions showed a preference
of about 8:1 for generation of the anti stereochemical relationship at the two new
stereocenters. Another noteworthy feature of this reaction is the successful reaction
between a relatively electrophilic radical and the acrylate moiety. Entry 6 has several
interesting aspects. The reaction proceeds by iodine atom transfer and the cyclization
mode is 9-endo. The initiation is by triethylborane and the reaction gives much higher
yields in water than in benzene. The efficiency of the cyclization and the solvent
sensitivity are probably related to reactant conformation. Entry 7 is another iodine
atom transfer cyclization initiated by triethylboron. Entry 8 involves 5-exo addition to
a alkynylsilane.

342
H. Miyabe, M. Torieda, K. Inoue, K. Tajiri, T. Kiguchi, and T. Naito, J. Org. Chem., 63, 4397 (1998).
343 H. Miyabe, M. Ueda, and T. Naito, Synlett, 1140 (2004).
344 H. Miyabe, M. Ueda, N. Yoshioka, and T. Naito, Synlett, 465 (1999); H. Miyabe, M. Ueda, N. Yoshioka,
K. Yamakawa, and T. Naito, Tetrahedron, 56, 2413 (2000).
345
H. Miyabe, M. Ueda, and T. Naito, J. Org. Chem., 65, 5043 (2000).