Page 1224 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1200 Scheme 13.37. Prelog-Djerassi Lactone Synthesis: R. W. Hoffmann and Co-Workers a

CHAPTER 13 B OH
H H
A 6 4 2
Multistep Syntheses 1) O CH O C
3
2
CH O C CO 2 H 1) BH CH O O BCH CH
3 2 3 MeO C 2 3
2 CH CH CH 3
CH CH 2) PCC 2) N(CH CH OH) 3 3 3
2
2
3 3 CH 3 CH 3 +
diastereomers
1) KOH
C
2) H+
E′ D CH
OH CH 3 3 CH 3
1) O , CH 3 O ,
6 4 2 3 O O 3
H C CH H 2 2 H H 2 2
2 2 + CO 2 O O
2) H O O purified H
CH 3 CH 3 CH 3
H from CH
CH 3
3
diastereomers
H H
D′ O CH CH O
O BCH 3 C ′ B′ 3
2
CH CH
1) DIBAL 3 3 H + PhCHNC CH 2 OH
6 4 CH O 2) Ph P CH H
H 2 C 3 2 O CH CH
3) K Cr O O separation of 3 3
diastereomers 3
CH 3 CH 3 2 2 7 CH
b
A′ 1) (+)-PhCHNH 2
2) BH -SMe
3 2
3) H O
2 2
CH 3
CH 3
O O O
a. R. W. Hoffmann, H.-J. Zeiss, W. Ladner, and S. Tabche, Chem. Ber., 115, 2357 (1982).
b. Resolved via -phenylethylamine salt; S. Masamune, S. A. Ali, D. L. Snitman, and D. S. Garvey, Angew. Chem. Int.
Ed. Engl., 19, 557 (1980).
by the stereogenic centers at C(2) and C(4) in the glutaric acid portion of the structure.
One of the centers reacted with a 97:3 preference with the achiral amine piperidine.
Two amide bonds are in
nonequivalent stereochemical
environments
(S) (R) (S) (S)
more reactive less reactive
In Step D another thiazoline chiral auxiliary, also derived from cysteine, was used
to achieve double stereodifferentiation in an aldol addition. A tin enolate was used.
The stereoselectivity of this reaction parallels that of aldol reactions carried out with
lithium or boron enolates. After the configuration of all the centers was established,
the synthesis proceeded to P-D lactone by functional group modifications.
A very short and efficient synthesis based on the desymmetrization principle is
shown in Scheme 13.39. meso-2,4-Dimethylglutaraldehyde reacted selectively with
the diethylboron enolate derived from a bornanesultam chiral auxiliary. This reaction
established the stereochemistry at the C(2) and C(3) centers. The dominant aldol
product results from an anti-Felkin stereoselectivity with respect to the C(4) center.