A decade ago we initiated research, the goal of which was isolation of a stable carbene. Our success has helped to catalyze a resurgence of interest in readily available and easily handled carbenes. Research on stable (nucleophilic) carbenes is again a popular theme worldwide. Efforts in the general area of stable carbenes now focus not only on chemistry of the carbenes themselves but also on their applications to other chemical systems, where their chemical properties create technical opportunities that are unavailable with other functional groups. The quest for isolable carbenes is a long saga whose origin can be traced back to the first half of the 1800s. A recently published history of this quest provides an important backdrop for the research described in this Account.1 It is the intent of this Account to delineate the events and environment that led to the report from DuPont laboratories of the first isolation of a stable crystalline carbene. Getting Started

Looking for Stable Carbenes: The Difficulty in Starting Anew

Chemistry and Biology of Mycotoxins and Related Fungal Metabolites

The power of cycloadditions for ring formation derives from the potential for chemo-, regio-, diastereo-, and enantioselectivity. Trimethylenemethane (TMM) and its equivalents offer the possibility of extending such benefits to the synthesis of five-membered rings. Three types of conjunctive reagents appear to be promising candidates: (1) selected 4-alky-lidene-4,5-dihydro-3H-pyrazoles, (2) 2-[(trimethylsilyl)methyl]allyl esters and halides, and (3) alkylidenecyclopropanes. Thermal reactions, especially intramolecular ones, effect the cycloaddition of the pyrazoles to olefins–especially electron-poor olefins. The latter two precursors require a catalyst, notably a palladium complex, to unlock the synthetic potential. With the 2-[(trimethylsilyl)methyl]allyl esters, a general chemo-, regio-, and diastereoselective cycloaddition with typical Diels-Alder dienophiles forms methylenecyclopentanes in both inter- and intramolecular fashion. A tin analogue allows extension of this cycloaddition to aldehydes, and, in a related sequence, to ketones and imines to form 3-methylenete-trahydrofurans and 3-methylenepyrrolidines with excellent diastereoselectivity. The 2-[(tri-methylsilyl)methyl]allyl esters also serve to effect net methylenecyclopentane annulation to cyclic enols. Such adducts can further undergo three-carbon intercalation or combined ring contraction-spiroannulation simply by the use of either a nucleophilic or electrophilic trigger. Alkylidenecyclopropanes undergo cycloadditions to both electron-rich and electron-poor olefins when stimulated by metal catalysts, especially palladium. A complementary regiochemistry to the approach based upon silicon conjunctive reagents is observed. The availability of these cycloadditions provides new strategies for the synthesis of natural products.

[3+2] Cycloaddition Approaches to Five-Membered Rings via Trimethylenemethane and Its Equivalents [New Synthetic Methods (55)]

Synthesis of Polyquinane Natural Products: An Update.

The tremendous potential of cyclopropenes and methylene-cyclopropanes as multifunctional reagents in organic syntheses has only been recognized in the last decade. The use of transition metal catalysts allows an effective control of their transformations enabling highly selecitive syntheses ranging from three- to sevenmembered carbocycles. The activities in this field are summarized in this review for the first time with an emphasis on the preparative aspects of this work.

Cyclopropenes and methylenecylopropanes as multifunctional reagents in transition metal catalyzed reactions

An enantiocontrolled cycloaddition approach to (+)-brefeldin A

Palladium-mediated cycloaddition approach to cyclopentanoid natural products. (.+-.)-Albene

The seco acid (X) is synthesized stepwise starting with the reaction between the ester (I) and the acetate (II).

Patrice Renaut

Papers

An enantiocontrolled cycloaddition approach to (+)-brefeldin A

Palladium-mediated cycloaddition approach to cyclopentanoid natural products. (.+-.)-Albene

Enantiocontrolled Cycloaddition Approach to (+)-Brefeldin A.

Diastereoselectivity of a [3+2]Annulation. On the Question of a Dipole Effect on Diastereoselectivity of Olefin Addition