Abstract

Trimethylenemethane (TMM) is a non-Kekulé molecule composed of four carbons, six hydrogens, and four π-orbitals. Therefore, TMM can only be expressed as resonance structures involving 1,3-diyls and zwitterions. The two degenerate nonbonding molecular orbitals in the Hückel molecular orbital of TTM indicate the existence of singlet and triplet electronic configurations, which play significant roles in the TMM chemistry.

TMMs were imaginary molecules until the late 1960’s, and parent TMM was first isolated in a low-temperature matrix. It is stable for several weeks at 77 K, and is a ground-state triplet with a D_3h-planar structure as assigned by ESR spectroscopy. The unique structures coupled with the complex electronic states of TMM derivatives have been topics of theoretical, mechanistic, and synthetic studies.

By analogy with the Diels-Alder reaction for the synthesis of six-membered rings through [4 + 2] cycloadditions, the use of TMM as a three-carbon unit for [3 + 2] cycloadditions appears to represent a viable synthetic possibility, because the four π-electron orbital system of TMM is theoretically suitable for the [4π_s + 2π_s] cycloaddition. As expected, however, rapid ring closure to methylenecyclopropane (MCP) is preferred to cycloaddition with a 2π acceptor. Therefore, for synthetic use, tailor-made derivatives of TMM and its equivalents need to be designed to achieve [3 + 2] cycloaddition reactions.

The first breakthrough in the use of TMMs for [3 + 2] cycloaddition reactions was reported in the reaction of isopropylidenecyclopentane-1,3-diyl, which has a considerable lifetime and reacts with electron-deficient alkenes.

Because the parent TMM gives methylenecyclopropane and many MCP derivatives undergo thermal isomerization, MCPs have been considered to serve as precursors for TMMs. However, direct evidence for the formation of TMMs from MCPs and their synthetic use as TMM precursors was rather scant until recently.

Since TMM species are generally too short-lived and too reactive to be used for organic synthesis, various attempts have been made to stabilize them with transition metal templates.

Efficient transition metal catalyzed TMM cycloaddition is achieved using MCPs and Ni(0) or Pd(0) catalysts. The reaction proceeds via ring opening of the MCP to form (methylene)metallacyclobutane-type intermediates.

More recently, Pd(0)-catalyzed reactions of [2-(acetoxymethyl)allyl]trimethyl-silane with 2π acceptors have emerged as a powerful method for cyclopentane synthesis. This reaction is considered to involve the zwitterionic TMM-Pd intermediate. The reaction serves well for the [3 + 2] cycloaddition to electron-deficient acceptors, and it has been applied to the synthesis of several cyclopentanoid natural products.

This review surveys the [3 + 2] cycloaddition reactions of TMMs and their metal complexes to 2π acceptors. The reactions are divided into five categories, defined by reaction types and precursors: (1) cycloadditions of free TMMs generated from diazenes, (2) cycloadditions of free TMMs generated from MCPs, (3) transition metal catalyzed reactions of MCPs, (4) transition metal catalyzed reactions of silylated allylic acetates, and (5) cycloaddition of stable TMM-metal complexes. Transformations that accomplish a net cycloaddition but require several steps using TMM equivalents are not covered. Various aspects of TMMs, including physical and synthetic chemistry, have already been reviewed.