Williams enantioselective synthesis

Williams.Knowles (1917- was born in Taunton, Massachusetts, and received his Ph.D. from Columbia University in 1942. ol-lowing his graduate studies, he began work at the Monsanto Coiii janv ill St. Louis, Missouri, wheie hu remained until his retirement in 1986. He received ihe 2001 Nobel Prize in chemistry for his work on enantioselective synthesis, one of the few non-academic scientists to be thus hoiiored. 

Nishioka, T., Iwabuchi, Y, Irie, H., and Hatakeyama, S., Concise enantioselective synthesis of (-t)-aspicilin based on a ruthenium catalyzed olefin metathesis reaction. Tetrahedron Lett.. 39, 5597, 1998. Williams, D.R., and Clark, M.P., The macrocyclic domain of phorboxazole A. A stereoselective synthesis of the Cj-Cjj macrolactone. Tetrahedron Lett., 40, 2291. 1999. 

Unfortunately, it s usually the case that only one enantiomer of a given drug or other important substance has the desired biological properties. The other enantiomer might be inactive or even dangerous. Thus, much work is currently being done on developing enantioselective methods of synthesis, which yield only one of two possible enantiomers. So important has enantioselective synthesis become that the 2001 Nobel Prize in Chemistry was awarded to three pioneers in the field William S. Knowles, K. Barry Sharpless, and Ryoji Noyori. 

Barrett AGM, Blaney F, Campbell AD, Hamprecht D, Meyer T, White AJP, Witty D, Williams DJ. Unified route to the pal-marumycin and preussomerin natural products, enantioselective synthesis of (—)-preussomerin G. J. Org. Chem. 2002 67 (9) 2735-2750. 

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

The biological activity and the interesting structure stimulated efforts towards its total synthesis. Evans and Calter reported the first synthesis by an efficient aldol method.4 Toshima and co-workers also succeeded in the total synthesis of bafilomycin Aj.5 This chapter is based on the enantioselective total synthesis by William R. Roush and co-workers, which was published in 1999.6... 

This chapter is based on the enantioselective total synthesis by William R. Roush and co-workers, which was published in 1999. ... 

Enantioselective homogeneous hydrogenation catalyzed by chiral transition metal complexes is one of the most well established transformations in asymmetric synthesis [1]. Excellent enantioselectivities have been achieved in the hydrogenation of a wide range of substrates, often with very low catalyst loadings. High reliability, mild reaction conditions, and perfect atom economy are further attractive attributes of this method. In particular complexes based on Ru or Rh have found broad application in industrial processes [1] and the impact of these catalysts has been recognized by the Nobel Prize awarded to Ryoji Noyori and William S. Knowles in 2001 [2]. 

Williams and co-workers reported the non-enantioselective total syntheses of the heptacyclic indole alkaloids notoamide B (227) and stephacidin A (225) (Scheme 43) [168], and of their probable biogenetic precursor, notoamide C (213) (Scheme 41) [169]. The notoamides are fungal indole alkaloids from Aspergillus species collected fi-om the common mussel Mytilus edulis off Noto Island in the Sea of Japan [170, 171]. There is also a synthesis of the closely related notoamide J (217) (Scheme 42) [172]. 

After screening a range of metal complexes based on iridium, aluminum, rhodium, or ruthenium toward their suitability to racemize (S)-l-phenylethanol, Williams and Harris et al. [12] demonstrated a proofof concept for the combination of such a metal-catalyzed racemization of 1-phenylethanol with an in situ enzymatic acylation of preferentially one enantiomer, although some Hmitations appeared such as limited conversion and the need for a range of additives. A representative example for this type of DKR is shown in Scheme 19.4 with the successful synthesis of the ester (R)-IO with enantioselectivity of 98% ee at 60% conversion. 

This synthesis illustrates the power of the elegant enantioselective seven-membered ring construction developed by the Davies group. The Williams phosphonium salt will also have general applicability. In a simpler manifestation, conversion of an aldehyde to, e.g., the enol benzoate, followed by exposure to dilute methoxide, will allow the conversion of an aldehyde to the aldehyde one carbon longer, without the acidic hydrolysis usually recpured for such a transformation. 

Meyers At, Williams DR, Erickson GW, White S, Druelinger M. Enantioselective alkylation of ketones via chiral, nonra-cemic lithioenamines. An asymmetric synthesis of a-alkyl and a,a -dialkyl cyclic ketones. J. Am. Chem. Soc. 1981 103 3081-3087. 

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