Page 72 - Advanced Organic Chemistry Part B - Reactions & Synthesis

44 Scheme 1.9. (Continued)

CHAPTER 1 Li +
– O
Alkylation of Enolates O O O
and Other Carbon f Ph PhCH SCH Br Ph
2
2
Nucleophiles 6 N O N O 83%
PhCH SCH 2
2
)
CH(CH 3 2 CH(CH ) 98:2dr
3 2
O O 1) LiHMDS O O
THF, – 78°C
O N CH 3 O N CH 3
7 g 2) PhCH 2 Br
CH Ph
CH 3 CH 3 CH CH Ph 2 94%
CH 3 CH Ph 3 2
2
94:6dr
O CH 3 O CH 3
CH 3 Ph 1) LDA, LiCl PhCH O Ph
2
8 h N N
2) PhCH OCH CH I CH
2
2
2
CH 3 OH 3 CH 3 OH
Li +
CH 3 CH 3 O – O CH 3 CH 3 O O
CH I PhCH O
3
9 h PhCH O N O 2 N O
2
CH 3
Ph Ph 64%, 3.6:1dr
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2886 (2003).
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stereochemical control by the auxiliary ring substituent. Entry 2 demonstrated the feasi-
bility of enantioselective synthesis of -aryl acetic acids such as the structure found
in naproxen. Entries 3 to 6 include ester groups in the alkylating agent. In the case
of Entry 4, it was shown that inversion occurs in the alkylating reagent. Entry 7 is
an example of the use of one of the more highly substituted oxazolidinone deriva-
tives. Entries 8 and 9 are from the synthesis of a neurotoxin isolated from a saltwater
bacterium. The pseudoephedrine auxiliary shown in Entry 8 was used early in the
synthesis and the 4-phenyloxazolidinone auxiliary was used later, as shown in Entry 9.
The facial selectivity of a number of more specialized enolates has also been
explored, sometimes with surprising results. Schultz and co-workers compared the
cyclic enolate H with I. 99 Enolate H presents a fairly straightforward picture. Groups
such as methyl, allyl, and benzyl all give selective -alkylation, and this is attributed
to steric factors. Enolate I can give either -or -alkylation, depending on the
conditions. The presence of NH or use of LDA favors -alkylation, whereas the use
3
99
A. G. Schultz, M. Macielag, P. Sudararaman, A. G. Taveras, and M. Welch, J. Am. Chem. Soc., 110,
7828 (1988).