Catalytic asymmetric hiyama cross-couplings of racemic α-bromo esters

Journal of the American Chemical Society

Volumn 130, Issue 11, 2008, Pages 3302-3303

  Dai, Xing ^a   Strotman, Neil A ^a   Fu, Gregory C ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA BROMO ESTER; ESTER DERIVATIVE; SILANE DERIVATIVE; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ARTICLE; ARYLATION; CATALYSIS; CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; CROSS COUPLING REACTION;

CATALYSIS; CROSS-LINKING REAGENTS; ESTERS; HYDROCARBONS, BROMINATED; MOLECULAR STRUCTURE; ORGANOSILICON COMPOUNDS; SILANES; STEREOISOMERISM;

EID: 41449104100     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja8009428     Document Type: Article

References (18)

1. For leading references to their pharmacology, see: Landoni, M. F.; Soraci, A. Curr. Drug Metab. 2001, 2, 37-51.
2. Strotman, N. A.; Sommer, S.; Fu, G. C. Angew. Chem., Int. Ed. 2007, 46, 3556-3558.
3. For reviews of the Hiyama reaction, see: (a) Denmark, S. E.; Sweis, R. F. In Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: New York, 2004; Chapter 4.
4. (b) Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61-85.
5. See the following for previous reports of catalytic asymmetric cross-couplings of alkyl electrophiles. (a) α-Halo amides: Fischer, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 4594-4595.
6. (b) Benzylic halides: Arp, F. O.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 10482-10483.
7. (c) Allylic halides: Son, S.; Fu, G. C. J. Am. Chem. Soc., ASAP. In each case, a chiral pybox ligand and an alkylzinc reagent are employed.
8. The susceptibility of α-aryl carbonyl compounds to racemization can complicate the development of catalytic asymmetric methods for their synthesis. For example, to date, highly enantioselective arylations of enolates have been limited to the formation of quaternary stereocenters. For an early study, see: Ahman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 1918-1919.
9. For leading references, see: Liao, X.; Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 195-200.
10. Notes: (a) In a gram-scale reaction, the cross-coupling illustrated in entry 1 of Table 2 proceeds in 80% yield and 90% ee.
11. (b) The ee of the product correlates linearly with the ee of the ligand.
12. (c) The ee of the product is constant during the course of the reaction.
13. (d) In the absence of an organosilane, no phenylation by TBAT is observed.
14. 3 furnished racemic product, perhaps due to the lability of the α stereocenter (in the case of aryl groups that are not electron-poor, control experiments establish that racemization of the product does not occur);
15. 3 was unsuccessful;
16. 3 underwent cross-coupling in moderate yield (44%) and ee (63%).
17. Under our standard conditions, n-hexyltrimethoxysilane and allyltrimethoxysilane did not participate in asymmetric Hiyama cross-couplings in good ee/yield.
18. Hydrolysis of BHT esters generally requires vigorous reaction conditions. For an example, see: Hattori, T.; Hayashizaka, N.; Miyano, S. Synthesis 1995, 41-43.