Academic literature on the topic 'Enolate reactivity'

Jeffrey C. Pelletier of Wyeth Research, Collegeville, PA has developed (Tetrahedron Lett. 2007, 48, 7745) a easy work-up Mitsunobu procedure for the conversion of a primary alcohol such as 1 to the corresponding primary amine 2. Shlomo Rozen of Tel-Aviv University has taken advantage (J. Org. Chem. 2007, 72, 6500) of his own method for oxidation of a primary amine to the nitro compound to effect net conversion of an amino ester 3 to the alkylated amino ester 5. Note that the free amine of 3 or 5 would react immediately with methyl iodide. Keith A. Woerpel of the University of California, Irvine has uncovered (J. Am. Chem. Soc. 2007, 129, 12602) a Cu catalyst that, with 7, effected direct conversion of silyl ethers such as 6 to the allyl silane 8. An Ag catalyst gave 9, which also shows arllyl silane reactivity. Biswanath Das of the Indian Institute of Chemical Technology, Hyderabad has established (Tetrahedron Lett. 2007, 48, 6681) a compact procedure for the direct conversion of an aromatic aldehyde such as 10 to the benzylic halide 11. This will be especially useful for directly generating benzylic halides that are particularly reactive. α-Sulfinylation of ketones often requires intial generation of the enolate. J. S. Yadav, also of the Indian Institute of Chemical Technology, Hyderabad, has devised (Tetrahedron Lett. 2007, 48, 5243) an oxidative protocol for installing sulfur adjacent to a ketone. In a related development, Richard S. Grainger of the University of Birmingham has established (Angew. Chem. Int. Ed. 2007, 46, 5377) a simple procedure for the conversion of thio esters such as 14 to the corresponding ketone 16. Yoshiya Fukumoto of Osaka University has shown (J. Am. Chem. Soc. 2007, 129, 13792) that a terminal alkyne 17 can be directly converted into the enamine 18 by Rh-catalyzed addition of a secondary amine. Lukas Hintermann and Carsten Bolm of RWTH Aachen have found (J. Org. Chem. 2007, 72, 5704) that inclusion of water gave the aldehyde, which could be oxidized with the residual Ru catalyst to the acid.

Ansa-bridged prodiginines include (+)-roseophilin B 3 and streptorubin B. The observation that streptorubin B potentiated apoptopic signaling in cell culture led to the development of obatoclax, currently being evaluated for the treatment of leukemia. Patrick G. Harran of UCLA devised (J. Am. Chem. Soc. 2013, 135, 3788) what promises to be a general route to the prodiginines, a key step of which was the cyclization of 1 to 2. In planning the synthesis of 1, the authors took advantage of the relative inertness of a monosubstituted alkene. Friedel-Crafts acylation of 5 proceeded smoothly without affecting the distal double bond. Reduction then completed the preparation of 7. The preparation of 1 continued from the pyrrole 9, prepared from the pyridine 8. Addition of the derived enoate to the aldehyde 10 proceeded smoothly, to give, after oxidation and acid-mediated rearrangement, the furan 12. Selective metalation followed by carboxylation gave the acid 13, which was combined with 7 to give 15. Deprotonation of 15 gave an intermediate that reacted primarily on the pyrrole N. This intermediate was then reacted with diethylchlorophosphite to give, after oxidation, the phosphoramide 16. Advantage was then taken of the organometallic reactivity of the monosubstituted alkene of 16, as Ru-mediated cross metathesis with 17 followed by reduction completed the preparation of 1. The diheteroaryl ketone of 1 is not enolizable. On exposure to KHMDS, the dialkyl ketone will be deprotonated reversibly. Either enolate could add to the diheteroaryl ketone, but only the adduct from deprotonation of the methylene could go on to alkene formation. This net dehydration may likely be driven by phosphoryl transfer to the intermediate alkoxide. The enone 2 is prochiral. Hydrogenation with an enantiopure catalyst proceeded with high de and 67% ee. Remediated intramolecular Friedel-Crafts addition of the dialkyl ketone to the pyrrole followed by acid-mediated rearrangement then delivered (+)-roseophilin 3. There are several points along this synthesis at which diversity could be introduced. This should enable detailed structure–activity studies of the prodiginines.