Suppression Of Racemization During The Scholarblogs (Page 4 of 4) in pdf

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In an effort to determine the generality of thii hiihly atereoeebctiie methodokqy, other exan@ee of this 1,4-

addition were performed, one of which involves the use d a catalylii source of copper and a Grignard ra&nt

in cuprate

formation16 (Table I, entry 10). Thii catalytic system pmvkJes the same enantioaebctffe tmnd aa shown in the previous

examples. Additional examples not depicted in Table

include di-n-butyl and his-trimethylsilylmethyl cuprates. These

examples were carried out as in entries 6-9, Table I and their reaction with 1 followed the previously defined (see Table I)

trends.

Noteworthy also is the diistem

’ My of these

organocuprate reactions with 1. We observe only one

diistereomer in each instance which we assign to be the trans&ans isomer based on wall eatablii

literature

precedents.4 Furthermore, NMR assignment of the protons Ha and Hb (Table I, &&

pmduced coupling constants, in all

cases measured , greater than 11 Hz (e.g.. &

JHaHpl 1.4lHz; a

JHsHb=l 1.63 Hz) inditing

a trans rel&onahii of

those protons.

As the mechanism of organccupmte reactions has been surrounded by controversy, many ideas, such as the

single electron transfer mechanism.2o have been proposed. Though the constraints this article do not tend themselves to

mechanistic discussion, we note that the observed mte retardation. in the presence of TMSCI, is con&tent with the

trapping of a cuprate/ substrate complex prior to the ratedetermining step. The results of our continuing efforts to

elucidate mechanistic aspects of thii study will appear in later publications.

In conclusion, we have demonstrated the stereo and enantiosalective C-3 functionaliitbn

of thiiutenoliie

1 via

1.4-addiiion of organocuprate reagents. Our results indiite that: (a) although racemization can mr

at elevated

temperatures (0°C and higher), the use of bw temperatures suppresses any racemization in these systems, and (b) if

higher temperatures are necessary (i.e., when using less reactive cuprates) the inclusion

,TMSCI

suppresses

racemization.

Acknowledgments:

We wish to thank the National Institutes of Health ford the funding of this research.

10.

11.

12.

13.

14.

15.

16.

17.

16.

19.

20.

Hanessian, S., Murray, P. J., and Sahoo, S. P. Tdahedmn

Left. 1095,26,5627-5630.

Hanessian. S., Murray, P. J., and Sahoo, S. P. Tefmhedmn I&f. 1086.26,5823-5026.

Hanessian. S., Murray. P. J., and Sahco. S. P. Tetmhdw

Len. 1986,26,5631=6634.

Harmssian. S. Atirichinkx

Acta 1989.22.3-13.

T&g&hi,

‘i., K&

K., and Yamt&,

S.‘Tefmhedmn 1976, 44 3547-3552.

Enantiomertc excaaa data obtaii

by conparison ot HPLC apectm of racer& and enantiomerically enriched

mate&s which utilized a Daicel Chiml Pak AS column, IBM HPLC unit and Hexanel iecpropanol aolvent systems.

Hanesaian, S., Hodges, P.J.. Murray, P. J., and Sahoo, S. P. J. C/mm. Sac., C/mm. Commur~. l-,754-755.

Kochi, J., Tamum, M., and Wada, K. J. Am. Chem. See. 1970,92,6656-6857.

House, H. O., DuBose. J. C. J. Org. Chem. lQ7b, 40,76&790.

Lipshutz. B. H. Synthesis 1987.325341.

Liishutz, 6.

H.. Oilhelm, R. S., and Lozbwski, J. A.. Tetrahedron lg84,40,5005-5036.

House, H. 0.. Chu, C. Y.. Wilkins. J. M.. and Umen, M. J. J. Cm. Chem. 197S.40,1460-1469.

Corey,.E. J., &az; N. W; Tetmhdon

Left. l-,26,

eOlS-eOg2.

Corey, E. J., Boaz, N. W. Tetrahedron Leit. 1984.26,3083-3066.

Corey, E. J., Boaz, N. W. T&ahedmn Le!t. lm.

2e, 601!%6018.

Kuwajima, I.. Nakamum, E., Matauzawa, S., and Horiguchi, Y. Tetrahedron Left. 1988,27.4025-4028.

Kuwajima, I., Nakamum, E.. Matsuzawa, S., andHoriguchi, Y. Tetrahedron Left. lg66,27,402g-4032.

For preparation and use of similar cupmtea: Lipahutz, 8. H., Moretti, Ft., and Crow, R. Org. Sp. lgg& 69,60-66.

Lipshutz, B. H., Ellsworth, E. L., Siihaan, T. J.,, and Shirazi, A. Tetnrhedmn Lett. 1988.29,6677-6660.

House, H. 0. Act. &em. &a.

lW6.9.59-67.

(Received in USA 11 May 1992; accepted 24 June 1992)

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