Keck stereoselective allylation

Asymmetric allylation of aldehydes with allylstannane in the presence of Lewis acid and chiral BINOL (or other chiral ligands). 

The enantioselectivity is imparted by the steric bias of the chiral ligands which displace wo-propoxide of titanium w -propoxide. Therefore, the chiral Lewis acid becomes Ti(0/-Pr)2(binol), which is substitutionally labile  

---

Evans aldol reaction Hajos-Wiechert reaction Keck stereoselective allylation Roush allylboronation... 

The total synthesis of Epothilone B 4, the first natural product (with Epothilone A) to show the same microtubule-stabilizing activity as paclitaxel (Taxol ), has attracted a great deal of attention since that activity was first reported in 1995. The total synthesis of 4 devised J. Org. Chem. 2008, 73, 9675) by Gary E. Keck of the University of Utah was based in large part on the stereoselective allyl stannane additions (e.g. 1 + 2 3) that his group originated. 

The Keck radical allylation is a representative example of a radical fragmentation reaction employing the reagent allyltributyltin in the allylation process. " The first synthesis of the Stemona alkaloid stenine by Hart in 1990 established an iodolactonization/Keck allylation (93 —> 94) sequence (Scheme 25.44) as a solution to the problem of stereoselective ethyl group installation. ... 

Keck has also described a mechanistic study of the intra-molecular allylations of Z-16 and -19 under a variety of conditions.These results are summarized in Scheme 5.2.4, as the Z-16 consistently gave the major product 18 upon treatment with Brpnsted and Lewis acids. The observed stereoselectivity is rationalized through the synclinal arrangement 17. 

The l,T-binaphthalene-2,2 -diol complexes of Lewis acids have received considerably more attention. Mikami hrst reported the apphcation of BtNOL/ri(IV) complexes for enantioselective allylations of glyoxylates.ii Keck" and Umani-Ronchi/Tagliavinin independently devised allylation procedures with (/ )-BtN0L/Ti(0-iPr)4 and (5)-BIN0L/Ti(0-iPr)2Cl2, respectively (Scheme 5.2.83). The use of molecular sieves is essential for high reactivity and stereoselectivity. 

The installation of the butyrolactone substituent at C3 started with the addition of the lithiated form of the ortho ester 121 to 120. The y-butyrolactone core was installed after stereoselective reduction of the ketone moiety and exposure to TsOH in methanol. Claisen rearrangement afforded 122 which resisted attempts to undergo iodocyclization, but afforded tetracylic 123 after selenolactonization followed by Keck allylation and a-methylation. The total synthesis of (—)-tuberostemonine (4) was concluded after 25 steps and in 1.7% overall yield from 113 after isomerization of the allyl group and cross-metathesis with ethylene promoted by ruthenium catalyst 117 to provide the terminal vinyl group which was stereoselectively hydrogenated. 

For the synthesis of (-)-magellanine and related Lycopodium alkaloids, Mukai et al. used a Ueno-Stork cycliza-tion coupled with a Keck allylation to generate an advanced intermediate. Thus, bromoacetal derivative 97 was exposed to conventional radical conditions in the presence of allyltributyltin to give the tricyclic compound 98 (after an oxidation step) with the quaternary carbon center formed and an allyl group installed stereoselectively (Scheme 25.46). 

---