S-tert-Butyl (2R*,3R*)- and (2R*,3S*)-3-tosyloxy-2,3-2H2-
butanethioate 3 and 4
Values for (kH/kD)syn are subject to much greater relative error
than (kH/kD)anti, because the values of the syn KIE depend
directly upon the very small percentage of syn elimination from
the (2R*,3S*) diastereomers. A worst-case analysis showed that
whereas (kH/kD)anti could have as much as 5% relative error, the
relative error for (kH/kD)syn could be as high as 25%.
◦
To 3.0 g (9.5 mmol) of esters 1 and 2 at 0 C (N2, stirring) were
added 3.0 molar equiv. TFA, and the mixture was allowed to return
to rt. After 13 h 1.2 molar equiv. of TFAA were added at 0 ◦C. After
1 hr 1.2 molar equiv. of 2-methyl-2-propanethiol were added and
the reaction was continued for 22 h, followed by an aqueous
workup (Et2O, H2O, NaHCO3, evaporation). Recrystallization
from hexane produced 3 (2.05 g, 65%), mp 46–47 ◦C and 4 (2.4 g,
Conclusion
◦
76%), mp 46–48 C. 3: dD (76 MHz; C6H6; C6D6) 2.19 (s, 2CD),
In conclusion, we have shown that contrary to earlier suggestions,
activation by a carbonyl group has virtually no influence upon
the stereoselectivity of base-catalyzed, 1,2-elimination reactions
of b-tosyloxybutanoate esters and thioesters, even though these
reactions take place at the E2–E1cB interface. Under conditions
in which aggregation phenomena and the complex conformational
effects of cyclic compounds play no role, electronic effects by
themselves do not seem to be a major determining factor leading
to syn elimination.
5.00 (s, 3CD); dH (200 MHz; CDCl3; Me4Si) 1.29 (3 H, s), 1.40
(9 H, s), 2.44 (3 H, s), 2.85 (1 H, br s), 7.31 (2 H, d), 7.81 (2 H,
d). 4: dD (76 MHz; C6H6; C6D6) 2.61 (s, 2CD), 5.00 (s, 3CD); dH
(200 MHz; CDCl3; Me4Si) 1.29 (3 H, s), 1.40 (9 H, s), 2.44 (3 H,
s), 2.59 (1 H, br s), 7.31 (2 H, d), 7.81 (2 H, d).
General method for elimination reactions of deuterated substrates
Stereospecifically deuterated tosyloxyester and thioester sub-
strates (250–800 mg) were stirred in 3 : 1 v/v EtOH–H2O in a
22–25 ◦C water bath with 10% molar excess KOH. Concentrations
were 1.6 M for 1 and 2 and 1.13 M for 3 and 4. Reaction times for
esters 1 and 2 were 7–8 min and for thioesters 3 and 4 were 30 s.
Reactions were quenched with 2–4 drops of acetic acid and then
neutralized with NaHCO3. Flash chromatography (SiO2/hexane–
Et2O), careful evaporation at rt or short path distillation, analysis
by capillary GC, and separation by preparatory GC led to the
recovery of deuterated 5 from ester substrates and 6 from thioester
substrates. The (Z)-alkene product from 3 was also recovered in
one experiment and was ∼99% deuterated at C-2. Alkenes 5 and 6
were analyzed by multiple 2H NMR integrations (C6H6) of samples
from two or more separate experiments. 5: dD (76 MHz; C6H6;
C6D6) 5.73 (s, 2CD), 6.82 (s, 3CD); dH (200 MHz; C6D6; C6H6)
1.34 (3 H, s), 1.41 (9 H, s), 5.75 (s); dH (200 MHz; CDCl3; Me4Si)
1.45 (9 H, s), 1.85 (3 H, s), 5.75 (s). 6: dD (76 MHz; C6H6; C6D6)
5.91 (s, 2CD), 6.69 (s, 3CD); dH (200 MHz; CDCl3; Me4Si) 1.46 (9
H, s), 1.81 (3 H, s), 5.95 (s).
Acknowledgements
We acknowledge the generous support of the National Science
Foundation (NSF Grant CHE-8505408) and the National In-
stitutes of Health (NIH Grant GM40018). Acknowledgement is
made to the donors of the Petroleum Research Fund, administered
by the American Chemical Society, for partial support of this
research. Student stipends were also provided by the Howard
Hughes Medical Institute and the 3M Foundation. We are grateful
to the National Science Foundation (CHE-8409822) and the
3M Foundation for funding the purchase of a 200 MHz NMR
spectrometer. We thank Dr Stephen B. Philson and the University
of Minnesota for making possible the acquisition of 76 MHz 2H
NMR spectra.
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1
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2
determined directly by multiple 76 MHz H integrations (C6H6)
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the (2R*,3R*) and (2R*,3S*) substrates, respectively.
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