David Marcoux

TfNH2 as Achiral Hydrogen-Bond Donor Additive to Enhance the Selectivity of a Transition Metal Catalyzed Reaction. Highly Enantio- and Diastereoselective Rhodium-Catalyzed Cyclopropanation of Alkenes Using α-Cyano Diazoacetamide

A highly stereoselective (up to 98% ee and 99:1 dr) Rh(II)-catalyzed formation of nitrile-substituted cyclopropanes is described. Alpha-cyano diazoacetamide reagents react with a variety of mono- and disubstituted olefins in good yields and excellent enantio- and diastereocontrol. Less reactive substrates, such as aliphatic olefins, also undergo the reaction. This new methodology features the unprecedented use of an achiral hydrogen-bond donor additive to enhance the selectivity and exploits the powerful trans-directing ability of amides solving the diastereocontrol issue of the formation of substituted 1-cyanocyclopropane-1-carboxy derivatives.

General Method for the Synthesis of Phenyliodonium Ylides from Malonate Esters: Easy Access to 1,1-Cyclopropane Diesters

A general method to access phenyliodonium ylides from malonates has been developed. These ylides provide easy access to a variety of useful 1,1-cyclopropane diesters using rhodium or copper catalysis. Moreover, the iodonium ylide of dimethyl malonate was obtained in 78% yield using improved conditions that involve a simple filtration step to isolate the desired product. This ylide was shown to be a safer and convenient alternative to the corresponding diazo compound and a very efficient way to 1,1-cyclopropane diesters when used with a catalytic amount of Rh(2)(esp)(2).

trans-Directing ability of amide groups in cyclopropanation: application to the asymmetric cyclopropanation of alkenes with diazo reagents bearing two carboxy groups.

Book: M. P. Doyle, M. A. McKervey, T. Ye Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides; Wiley-VCH: New York, 1998. Comment: The authors propose an intriguing mechanistic pathways to explain the selectivity in the cyclopropanation with diazo reagents bearing two carboxy groups. It is proposed that the chiral rhodium complex preferentially binds to one face of 1, thereafter the amide substituent acts as a “trans-directing group” and promotes the formation of only one diastereomer. The enantioselectivity is shown to depend on both the ligand used and the substituents on the amide nitrogen. The yields are moderate to good for a variety of alkenes, although aliphatic olefins give poor results. Derivatizations of the resulting products, such as reduction, ring opening and esterification are demonstrated. R1 = OBu, Ph, Ar, Hetar, styryl R2 = H, Me 14 examples 24–92% yield 84–97% ee [Rh2(S-nttl)4] (1 mol%)

trans-Directing Ability of the Amide Group: Enabling the Enantiocontrol in the Synthesis of 1,1-Dicarboxy Cyclopropanes. Reaction Development, Scope, and Synthetic Applications

In this article, we describe our efforts toward the enantioselective formation of 1,1-cyclopropane diesters via the metal-catalyzed cyclopropanation of olefins. The strategies envisioned to achieve such a goal are discussed as well as the results that led us to the discovery of the powerful trans-directing ability of the amide group in Rh(II)-catalyzed cyclopropanation reactions. We show how this feature enables a solution for the stereoselective synthesis of 1,1-dicarboxy cyclopropane derivatives. The scope and limitations are discussed as well as the demonstration that these newly formed cyclopropanes display reactivity similar to that of 1,1-cyclopropane diesters. Conversely, 1,1-cyclopropane diesters could be accessed in two steps from commercially available alkenes. The potential utility of this methodology is illustrated by several functional group transformations and its use in the expedient stereoselective formal synthesis of (S)-(+)-curcumene, (S)-(+)-nuciferal, (S)-(+)-nuciferol, (+)-erogorgiaene, (+/-)-xanthorrhizol, and (+/-)-2-hydroxycalamenene.

Effect of counterion structure on rates and diastereoselectivities in α,β-unsaturated iminium-ion Diels-Alder reactions.

The use of cyclic α,β-unsaturated iminium-ion dienophiles is documented in two highly diastereoselective Diels-Alder (DA) reactions. The dienophilic counterion was found to have a significant effect on reactivity.

Protected Chloroethyl and Chloropropyl Amines as Conformationally Unrestricted Annulating Reagents

The purpose of this letter is to document the use of protected chloroethyl and chloropropyl amines as conformationally unrestricted ambiphilic reagents that undergo annulation reactions with Michael acceptors. This reaction is wide in scope and utilizes reagents that are commercially available, inexpensive, and stable. Furthermore, this reaction is easy to execute and proceeds rapidly.