Cyclopropane derivatives methylenecyclopropane

If one analyzes the rotation of D-a-(methylenecyclopropyl)glycine (82) the optical activity must come from (at least) four sources. One rotation contribution is associated with the atomic asymmetry of the open-chain moiety (methylenecyclopropane being viewed as a ligand). On the other hand, optical activity will also be induced by the asymmetric carbon atom of the ring and the asymmetry in the electron density distribution of the exocyclic double bond system (with diastereotopic faces). Finally also helix optical activity may be operative. The example of 82 demonstrates the complexity of the optical rotation of an apparently simple cyclopropane derivative. Further discussions of optical rotations of similar compounds, therefore, will cling to only the qualitative level. 

This section reviews the reactions of methylenecyclopropanes functionalized at the double bond generating cyclopropane derivatives. 

Abstract Transition metal-catalyzed cycloadditions of cyclopropanes have been well developed over the past several decades, leading to numerous new types of cycloadditions which are complementary to the traditional cycloadditions for the synthesis of carbocycles. Cycloadditions of vinylcyclopropanes (VCPs) and methylenecyclopropanes (MCPs) constitute two main aspects of this field. VCPs can act either as five-carbon synthons or three-carbon synthons, depending on whether the vinyl substituent is acting as an additional two-carbon synthon or not. As five-carbon synthons, VCPs are involved in [5-1-1], [5-1-2], [5-I-2-1-1], and [5+1+2-I-1] cycloadditions. As three-carbon synthons, VCPs are mainly involved in [3-1-2] and [3-1-2-t-l] cycloadditions. MCPs mostly act as three-carbon synthons and can have [3-1-2] cycloadditions with different jt systems. Other types of cycloadditions involving MCPs are also reviewed, such as [3-rl], [3+2+2], and [4+3+2] cycloadditions. CycloadditirMis of some other unusual cyclopropane derivatives are also introduced briefly. The cycloadditions of VCPs and MCPs have found applications in total synthesis and some representative molecules are tabulated as selected examples. 

Cyclopropanation ([2 +1] Cycloaddition). Cu - and Rh -catalyzed cyclopropanation of olefins with dimethyldiazo malonate was used efficiently for the preparation of cyclopropane dicarboxylates. Methylenecyclopropanes were employed in this reaction to afford bicyclopentane derivatives in moderate yields and high diastereoselectivity (eq 17). Utilization of dimethyl diazomalonate in enantioselective cyclopropanation is a very challenging task. Thus the highest ee s obtained in the presence of Rh2(45-MEAZ)4 did not exceed 50% (eq 18). Cyclopropanation of olefins was also performed in the presence of catalytic amounts of copper(II) and osmium(II). ... 

The kinetics of these reactions in comparison with those for methylenecyclo-propane analogs of compounds 160 have been studied by following the progress at pressures up to 3 kbar by on-line FT-IR spectroscopy [129]. The rate-enhancing influence of the additional strain in 160 overcompensates the expected retarding effect of the increased steric shielding by the second cyclopropane unit in 1 compared to methylenecyclopropane, and the cyclization rates for compounds 160 were faster by a factor of 6.8 to 8.1 in comparison with the corresponding methylenecyclopropane derivatives. 

These reactions of 1-Me resemble that of (dichloromethylene)cyclopropane [31] and radicophilic alkenes with a capto-dative substitution pattern [32]. Thus, it is not surprising that 1-Me reacts with a-ferf-butylthioacrylonitrile (18), yielding the two isomeric cyclobutane derivatives 19a, b (ratio 2.2 1) as a mixture of two diastereomers each [29] (Scheme 5), and this reaction occurs under milder conditions than the [2-1-2] cycloaddition of 18 onto methylenecyclopropane. 

There is no published example of a cyclopropanation of the double bond in chlorocyclopropylideneacetate 1-Me with retention of the chlorine atom. Thus, attempted cyclopropanations under Simmons-Smith [37] or Corey [38] conditions failed [25]. The treatment of the highly reactive methylenecyclopropane derivative 1-Me with dimethoxycarbene generated by thermal decomposition of 2,2-dimethoxy-A -l,3,4-oxadiazoline 26 (1.5 equiv. of 26,PhH, 100 °C,24 h),gave a complex mixture of products (Scheme 7) [39], yet the normal cycloadduct 28 was not detected. The formation of compounds 29 - 33 was rationalized via the initially formed zwitterion 27, resulting from the Michael addition of the highly nucleophilic dimethoxycarbene to the C,C-double bond of 1-Me. The ring closure of 27 to the normal product 28 is probably reversible, and 27 can rearrange or add a second dimethoxycarbene moiety and a molecule of acetone to form 33. 

At elevated temperatures, methylenecyclopropane and its derivatives undergo a rearrangement which maintains the methylenecyclopropane skeleton. Obviously, for the parent system this process is degenerate [216, 217-222]. The 2,2-dihalo-methylene-cyclopropanes behave analogously, providing either mixtures of the... 

Similarly, partially fluorinated and perfluonnated methylenecyclopropanes [87, 82], cyclopropenes [85, 84, 85], cyclobutenes [75, 86], and bicychc alkenes [87, 88, 89, 90] apparently derive dienophihc reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [2+4] cycloadditions [87, 82] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [2+2] cycloadditions [87]... 

Path a involves unimolecular decomposition of an initial ozonide (VI). It is important to note that since other methylenecyclopropane derivatives, such as 2,3-dimethylmethylenecyclopropane, do not undergo ring opening of the cyclopropane ring, both ring strain and the presence of the carbomethoxy groups must be necessary for such an unusual decomposition of an initial ozonide. The following sequence rationalizes... 

For R = H and Me, the derived values are [321.3 ( >1.9)] and [323.3 ( >1.4)] klmoF , respectively. A value of [326 ( > 4)] kJmoF for AHf(g, 1,2,3-butatriene) is thus credible. What is found for the cyclopropanation enthalpies of butatriene There are seemingly no relevant data for either of its monocyclopropanation products, dimethylenecyclopropane (25a) or vinylidenecyclopropane (25b). The two dicyclopropanation products have comparable enthalpies of formation dicyclopropylidene (26), 286.6 (1) and 324.3 (g), and meth-ylenespiropentane (27), 287.0 (1) and 320.9 (g), respectively". The 2-6 kJ moF decrease in enthalpies of formation for gaseous dicyclopropanated products is not particularly in accord with the 3 kJ moF increase per alkyl substituent of cyclopropanation of simple olefins. However, in that the allene —> methylenecyclopropane —> spiropentane (3 23 7) enthalpy of formation changes are still enigmatic, and error bars are absent for the dicyclopropanated products, we do not fret. But we eagerly await more thermochemical data. 

A remarkable dependence of the reactivity on ring size has been found in the series of methylenecycloalkanes (Fig. 9) [106]. The exceptionally low rate constant for methylenecyclopropane indicates that the low solvolysis rates of cyclopropyl derivatives [154] are not only caused by the unfavorable change of hybridization of one ring carbon in cyclopropane but also by the low stability of the cyclopropyl cation relative to a compound with the same hybridization (methylenecyclopropane). The destabilization of the cyclopropyl cation must actually be greater than indicated by the numbers in Fig. 9 as the transition state of the electrophilic attack may already profit from the stabilizing ring-opening process (cf., Section III.B.2). 

The nickel(0)-catalyzed codimerizations of methylenecyclopropane (26) or 2,2-dimethylmethylene-cyclopropane with the chiral derivatives of acrylic acid lead to optically active 3-methylenecyclopen-tanecarboxylic esters or amides (39 equation 16) in good yields (Table 3). When (-)-camphorsultam acrylate is used, 3-methylenecyclopentanecarboxylic amides are obtained in up to 98% de. °... 

An attempt has been made to extend the discussion to the unsaturated derivatives of cyclopropane, i.e cyclopropene and methylenecyclopropane however, the treatment is not extensive either due to a paucity of pertinent chemistry or to coverage elsewhere in this volume (Cyclopropenes, Chapter 21 Cyclopropenyl derivatives. Chapter 24). The reader will also note that the discussion on basicity of cyclopropanes is considerably more extensive due to the wealth of new chemistry and conceptualizations in the past dozen or so years. 

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