Spiropentane, reaction

The earlier examples of [2 + 1] cycloaddition of a carbene (or carbenoid) on the double bond of alkylidenecyelopropanes to yield spiropentane derivatives were observed as undesired side reactions in the synthesis of alkylidenecyelopropanes through the addition of a carbene to a substituted allene [161]. In some cases the spiropentane derivative was obtained as the major product [161a, c] especially when a large excess of the carbene reagent was used. For example, when methyl 3,4-pentadienoate (610) was treated with a ten-fold excess of methylene iodide and zinc-copper couple the two products 611 and 612 were isolated in 1 4.5 ratio (Scheme 86) [161a]. 

The rhodium acetate catalyzed addition of ethyl diazoacetate to MCP (1) gave spiropentane 619 in high yield (Scheme 89) [6e]. The same compound 619 was obtained in lower yield by a Simmons-Smith reaction to methylenecyclo-propane 217 [164],... 

An asymmetric synthesis of the spiropentanes 630, albeit with low enantiomeric excess, was achieved by the reaction of allenes 629 with diazomethane in the presence of an optically pure copper (II) chelate complex (R) or (S)-631 (Scheme 94) [170],... 

Vinylbuta-1,3-diene produces the 1,2- and 3,4-mono-insertion adducts with dichlorocarbene in a 4 1 ratio [37]. A similar preference in reactivity is observed with 3-methylene-cyclohexenes [90]. 1,2-Dienes react with two equivalents of dichlorocarbene to form spiropentanes [21, 90] (Scheme 7.6). Spiropentanes (50-95%) are also obtained from methylenecyclopropanes [36,106] and by the reaction of electron-deficient alkenes with an excess of chloroform [31] (see Scheme 7.12)... 

Many reducing agents are capable of severing a carbon-halogen bond. Cathodic cleavage provides perhaps the most versatile method, and has been put to excellent use. The electrochemical variation of the Wurtz reaction constitutes a powerful method for the construction of a variety of rings, particularly strained systems. Dramatic examples are provided by the assembly of bicyclobutane (308) [89], bicyclohexene (310) [90-92], [2.2.2]propellane (312) [93], spiropentane (316) [94], j -lactams 318 [95], and a variety of small-ring heterocycles (320) [96,97]. 

Reaction of the chloro ester 1-Me with the enol silyl ether 23 a in the presence of dimethylaluminum chloride afforded the [2-1-2] cycloadduct 20 (67% yield) (Scheme 6). Deprotection of the alcohol moiety with uBu4NF in THF gave an 83% yield of a mixture of the 5-keto ester 21a and the spiropentane derivative 22 (ratio 1 90). Upon running the reaction in a mixture of THF/water (ratio 1 1) instead of anhydrous THF, the 5-keto ester 21a was isolated exclusively [331. 

MIRC and MIMIRC Reactions Leading to Spiropentanes, Tricyclo[3.2.1.0 ]octanes and Other Tricyclic Skeletons... 

The Michael addition followed by Intramolecular Ring Closure (MIRC) reactions have been recognized as a general synthetic approach to carbocyclic three-membered ring derivatives [1]. The enhanced Michael reactivity of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) towards thiolates, alkoxides, lithiated amides and cyclohexadienolates (see below) allows one to perform highly efficient assemblies of spiropentane, tricyclo [3.2.1.0 ]octane, bicyclo [2.2.2] octane... 

Scheme 63. The formation of spiropentane derivatives 218,219,224 via MIMIRC reactions of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) [10c,21 a, 53]...

The reaction has been extended to the chemo- and enantioselective cyclopropanation of polyenes (equations 84 and 85) and allenic alcohols that afforded spiropentane derivatives . 

Substituted cyclopropylidenes have been shown to participate in both inter-and intramolecular addition reactions with olefins. The resulting products are spiropentane derivatives as well as carbene dimers which are formed as side-products [99, 100]. In the absence of olefinic reaction products the latter may even become the main products [99 b],... 

In contrast, carbon vapor generated in a carbon arc deposits mixtures of thermally equilibrated C(1S), C(3D), and C(3P) atoms on the walls of the reaction vessel, where they can be reacted with olefins.16 The most energetic and shortest-lived species, CX S), apparently forms allenes and inserts into C—H bonds. The Q1/)) atoms yield spiro-pentanes by two stereospecific addition steps. After long periods only ground state C(3P) atoms remain, and they add to olefins partially stereospecifically as shown below to yield isomeric spiropentanes. 

Concerted versus stepwise issue was studied for another radical reaction. The thermal denitrogenation of 4-spirocyclopropane-l-pyrazolines (27) gives alky-lidenecyclobutanone (28) and spiropentane (29) in three possible pathways (Scheme 5), via (a) diazenyl diradical intermediate (30), (b) 1,3-diradical intermediate (31), or (c) concerted cycloreversion TS. 

Computational study at (U)B3LYP/6-31G for the reaction of 27 (R = Z = H) showed that the activation barrier (AE + ZPE correction) for the diradical (31) formation (path b) is 40.2kcal mol, which is 2.1 kcalmol-1 lower than that for the diazenyl diradical (30) formation step (path a).44 The barrier from 31 to 29 is very small (0.6 kcal mol ), whereas the barrier from 31 to 28 is 7.0 kcal mol-1. Direct formation of 28 from 27 via a [2 + 2 + 2] reaction did not give TS. Thus, the calculations suggested that the reaction of 27 (R = Z = H) would give 29 as a major product via path b. This is consistent with experimental report, which showed that the denitrogenation of the parent 27 nearly exclusively gave spiropentane.45... 

In order to reconcile this discrepancy, dynamics effect was examined by means of ab initio MD simulations at (U)B3LYP/6-31G. 44 Trajectories were initiated at the TS for the denitrogenation from 27 (R = Z = H) to 31 with 353 K Boltzmann distribution for the reaction coordinate translation. Out of 10 trajectories, 1 went back to the reactant, 8 gave 31, and 1 led directly to 29. Thus, the trajectory calculations reproduced experimental trend reported in the literature,45 namely spiropentane is the major product for the reaction of the parent 4-spirocyclopropane-l-pyrazoline. 

Oxaspiropentanes have been obtained from the cyclopropylide 103, prepared by treatment of cyclopropyldiphenylsulfonium tetrafluoroborate 102 either with sodium methylsulfmyl carbanion in dimethoxyethane at —45 °C or with potassium hydroxide in dimethylsulfoxide at 25 °C. While the reaction of the ylide 103 with a,p-unsaturated carbonyl compounds has resulted in selective cyclopropylidene transfer to the a, 3-carbon-carbon double bond leading to spiropentanes, condensation of 103 with non-conjugated aldehydes and ketones led to oxaspiropentanes such as 104, which have been isolated in 59-100% yields, Eq. (30) 57). 

The reactions of a,P-unsaturated esters having an a-hydrogen with haloform and base can lead to spiropentanes or methylenecyclopropanes 203 204) ... 

Polymerization. Monomers. The cyclopropane type monomers are prepared either by addition of the dichlorocarbene or by the Simmons-Smith reaction on the corresponding olefins. Most of these compounds have been described. Spiropentane is prepared by the Applequist method (I, 2), by the reaction of zinc with C(CH2Br)4 in alcohol in the presence of ethylenediaminetetraacetic acid (EDTA). This hydrocarbon is purified until a single NMR signal is obtained at t = 9.28. 

The difficulty in obtaining this monomer in the pure state arises from the fact that the known methods of preparation involve the simultaneous formation of considerable amounts of the isomers of spiropentane which are difficult to remove. The method adopted as giving the most satisfactory yields is that of Applequist, Fanta, and Henrickson (I, 2). The spiropentane is prepared by reaction of zinc dust with pentaerythrityl tetrabromide in alcohol in presence of the sodium salt of ethylenediamine-tetraacetic acid as complexing agent. The yield of hydrocarbon (spiropentane plus various ethylenic compounds) is of the order of 84%. The spiropentane is obtained in the pure state by treating the mixture with bromine in dibromomethane. The yield of pure spiropentane was found to be 62%. 

In analogy with the spiropentane to methylenecyclobutane rearrangement, one may expect that kinetic studies on 1-methylenespiropentane will be on interest. Thermal reactions of substituted methylenespiropen-tane have just been reported 33>. 

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