3685665732

WYKŁADY PLENARNE I ZAPROSZONE

CONQUERING ONE OF THE LAST BASTIONS IN ORGANIC SYNTHESES — CATALYTIC ASYMMETRIC C-C BOND FORMATION IN >99% EE VIA ZACA-PD OR CU-CATALYZED CROSS-COUPLING

Ei-ichi Negishi*. Shiqing Xu, Akimichi Oda, and Yohei Matsueda

H. C. Brown Laboratories of Chemistry, Purdue University, West Lafayette, IN, USA E-mail: [e-mail]_

Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) is a catalytic asymmetric C-C bond forming reaction, which has been used to significantly modernize and improve syntheses of natural products including deoxypolypropionates, isoprenoids, and other heterocyclic compounds of biological and medicinal interest.¹'¹ Some key features of the ZACA reaction include (i) catalytic asymmetric C-C bond formation, (ii) use of alkene substances of one-point-binding without requiring any other functional groups and, (iii) many potential transformations of the initially formed alkylalane intermediates.

Here we will present the recent advances in ZACA reaction for highly enantioselective syntheses of various /?- and more-remotely chiral 1-alkanols of >99% ee.¹²¹ ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected co-alkene-l-ols protocols were applied to synthesis of both (R)- and (S)-difunctional intermediates 1 and 3 in 80-90% ee, which were further purifted to provide enantiomerically pure (>99% ee) compounds 1-4 by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of a broad array of chiral compounds including those of isotopomers in excellent enantiomeric purity (>99% ee) by introducing various carbon groups via Cu- or Pd-catalyzed cross-coupling without epimerization.

(1)(-)*ZACA (SI"^1’ i^93*	,
	RŁA^oh
>99% ee (B), hydrolysis	'>99%ee
	MMbJ

Scheme 1. Strategy for the synthesis of 2-alkyl-1-alkanols of of >99% ee.

R^I^^^OZJ

) Oj		^<ii,=™m^,,Z6d	Rl^on
^i( ImM “on	(R|-3, >99% ee	fili) TBAF desilylalion

R^ai-^A^-OZ

AcO^J^OZ	asr.™.
(SH. *99% «9		>99% ee

of >99% ee.

Scheme 2. Strategy for the synthesis of y-

[2] (a) Xu, S.; Lee, C.-T.; Wang, G.; Negishi, E. Chem. Asian J. 2013, 8, 1829. (b) Xu, S.; Oda, A.; Kamada, H.; Negishi, E. Proc. Natl. Acad. Sci. USA 2014, 111,8368.

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(a) Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 10771. (b) Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1996, 118, 1577. (c) Negishi, E. Angew. Chem. Int. Ed. 2011, 50,6738. (d) Xu, S.; Negishi, E. Heterocycles 2014, 88, 845.