1994 Merck Frosst Award Lecture New strategies for the stereoselective synthesis of natural and unnatural products via organometallic reagents and catalysts

Abstract

Samarium in the presence of diiodomethane selectively cyclopropanates an allenic alcohol to yield a methylenecyclopropane with modest to excellent diastereoselectivity. The effect of substituents at the carbinol carbon and the allenic carbon on the diastereoselectivity was investigated. A palladium catalyst was shown to promote the intramolecular cycloaddition of the methylenecyclopropane with an electron-deficient alkyne to yield a methylenecyclopentane. The reaction was stereospecific with retention of stereochemistry as proven by X-ray diffraction. Nickel catalysts accelerate the hydroalumination of oxabicyclo[3.2. llalkenes, leading to bicyclic trialkylalanes. Upon treatment with a Lewis acid (diisobutylaluminum chloride), the trialkylalanes fragment to provide cycloheptenols. This reaction, followed by an enantioselective enzyme-catalyzed esterification, was used as a key step in a synthesis of the mevinic acid lactone.Key words: methylenecyclopropane, palladium, stereocontrol, oxabicyclic, nickel.Resume : Le samarium, en presence de diiodomtthane, transforme ~Clectivement un alcool allCnique en mtthylknecyclopropane avec une diasttrCosClectivitt allant de modeste ?I excellent. On a CtudiC l'effet d'un substituant port6 par le carbone carbinolique, et par le carbone alltnique, sur la diastCrCosClectivitC. On montre qu'une catalyse par le palladium favorise la cycloaddition intramoltculaire du mCthylknecylopropane, avec un alkyne deficient en tlectron, pour donner un mCthylknecyclopentane. La reaction est stCrCospCcifique avec rktention de la stCrCochimie tel que I'indique la diffraction de rayons X. La catalyse par le nickel acctlkre I'hydroalumination des oxabicyclo[3.2.l]alcknes conduisant aux trialkylalanes bicycliques. Ces trialkylalanes trait& par un acide de Lewis (chlorure de diisobutylaluminium) se fragmentent pour donner des cyclohepttnols. On utilise cette reaction suivie d'une esterification catalysCe par une enzyme CnantiosClective comme Ctape clC dans une synthkse de la lactone de I'acide mCvinique.Mots clbs : mCthylknecyclopropane, palladium, stCrkocontr6le, oxabicyclique, nickel.[Traduit par la rCdaction] New reactions and strategies are important for the stereoselective synthesis of natural and unnatural products having interesting architectures and (or) biological activity. Results are '

“Cut and Sew” Transformations via Transition-Metal-Catalyzed Carbon–Carbon Bond Activation

“…12 When ACPs 11 containing C 3 stereocenters were employed, retention of the stereo-information was obtained (Scheme 6). The acetylenic substituent has a marginal effect on the stereoselectivity.…”

“…The Lautens group later studied the stereochemistry of this reaction . When ACPs 11 containing C 3 stereocenters were employed, retention of the stereoinformation was obtained (Scheme ).…”

Synthesis of Methylene- and Alkylidenecyclopropane Derivatives

“…In order to gain selectivity and make the process synthetically useful, Lautens and co-workers have recently explored a large number of cyclopropanation procedures by methylene carbenoids to R-allenic alcohols. The Molander cyclopropanation procedure employing Sm and methylene iodide (or CH 2 ClI) in THF, proved to be highly selective, providing ACP alcohols with the exclusion of double cyclopropanation (Scheme 7), 19,20 as expected on the basis of the need of a free allylic hydroxyl moiety for effectiveness of the method. A detailed study of the diastereoselectivity of the cyclopropanation reaction has been carried out using a variation of the substituents at both ends of the allene and especially at the hydroxylbearing carbon atom.…”

“…The same cyclopropanation method has also been used to obtain enantiomerically enriched methylenecyclopropanic alcohols (see section V.B) 19 and deuterated methylenecyclopropanes by replacing the methylenation reagent with CD 2 I 2 . 21 MCPs 21 and 22 have been utilized for the synthesis of bicyclic cyclopentanotetrahydrofurans 29 by transition metal-catalyzed intramolecular [3 + 2] cycloaddition reactions [20][21][22][23] and for the synthesis of homoallylic alcohols 30 or bis(stannylated) compounds 31 by ring-opening hydrostannylation with different catalysts 24 (Scheme 8). The replacement of HgCl 2 in this Sm-mediated cyclopropanation procedure by different activating agents has recently been studied.…”

PdCl2-promoted reactions of diaryl-substituted methylenecyclopropanes

“…Methylenecyclopropanes (MCPs) 1 are highly strained but readily accessible molecules that have served as useful building blocks in organic synthesis. 1 The transition metal-mediated chemistry of MCPs 1 has been widely explored during the past few decades and the developments in this field have been comprehensively reviewed by Binger, 2 Donaldson, 3 Lautens, 4 Yamamoto, 5 Rubin and Gevorgyan. 6 Besides transition metals, Lewis acids such as Ln(OTf) 3 (Ln = Yb, Sc, La, etc.)…”