Divinylcyclopropanes synthesis

In contrast to the synthesis of carbocyclic rings, the Cope rearrangement has been used sparsely for generating azepinones. Recently, the enantioselectivity of the conversion of 2-aza-divinylcyclopropane 286 has been investigated. The synthesis started from the optically active cyclopropanecarboxylic acid (90% ee), which had been converted into the isocyanate 286 by initial azidation to 285 and a consecutive Curtius rearrangement. Furthermore, the conditions of the iso-... 

Entry 2 illustrates the reversibility of the Cope rearrangement. In this case, the equilibrium is closely balanced with the reactant benefiting from a more-substituted double bond, whereas the product is stabilized by conjugation. The reaction in Entry 3 involves a cz s-divinylcyclopropane and proceeds at much lower temperature that the previous examples. The reaction was used in the preparation of an intermediate for the synthesis of pseudoguiane-type natural products. 

Rhodium(II) (iV-dodecylbenzenesulfonyl)prolinate has been found to act as an effective catalyst for the enantioselective decomposition of vinyldiazoacetates to c -divinylcyclopropanes. Combination of this process with a subsequent Cope rearrangement has resulted in a highly enantioselective synthesis of a variety of cycloheptadienes containing multiple stereogenic centres (see Scheme 40). The tandem... 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

Entry 3 in Scheme 6.11 illustrates the application of a c/s-divinylcyclopropane rearrangement in the prepartion of an intermediate for the synthesis of pseudoguaiane-type natural products. 

The Cope rearrangement is of great importance as a synthetic method e.g. for the construction of seven- and eight-membered carbocycles from 1,2-divinylcyclopropanes and 1,2-divinylcyclobutanes respectively (e.g. 11 12), and has found wide application in the synthesis of natural products. The second step of the para-Claisen rearrangement is also a Cope rearrangement reaction. 

More recently, an analogous combination of lithium, magnesium, zinc and copper reagents led to the stereocontrolled synthesis of cyclopropanes, illustrated for the synthesis of fran -divinylcyclopropane (equation 33)84. 

An elegant application of this chemistry to the formal synthesis of ( )-quadrone has been reported by Piers and coworkers.78a l2la Decomposition of ethyl diazoacetate in the presence of the bicyclic structure (119) resulted in selective cyclopropanation to form (120). Further modification of (120) generated the /ram-divinylcyclopropane (121), which on thermolysis followed by desilylation produced the tricyclic system (122). Conversion of (122) to the ketone (123) completed the formal synthesis because (123 Scheme 24) had been previously converted to ( )-quadione.l2lb... 

The following references contain additional examples of this method and corresponding reaction types Synthesis of 3-fluoroethyl-2-cyclopenten-l-ones [35], preparation of functionalized bicyclo[5.3.0]decane systems and conversion of 1,2-divinylcyclopropanes to functionalized cycloheptanes [36] e.g. karaha-naenone [37], ( )-/Thimachalene [38][39]. Metal-catalyzed ring expansions in which cyclopropane (e.g. [40] [41] [42] [43] [44]) or aziridines (e.g. [45] [46]) and diaziridines (e.g. [45]) function as essential moieties are well known reactions. 

The Cope reairangement of 1,2-divinylcyclopropane systems in which one of the vinyl groups is part of an a,3-unsaturated ketone moiety has found considerable use in synthesis. A significant number of substrates have been prepared and subjected to thermal rearrangement and some of the products have been employed effectively for natural product syntheses. 

The key intennediate for the synthesis of ( )-sinulaiene (159), a structurally unusual marine natural product, was the bicyclic divinylcyclopropane (160). Successful Cope rearrangement of this substance would be expected to proceed via the endo isomer (161) to produce the bicyclo[3.2.1]octa-2,6-diene (162), possessing the correct stereochemistry at C-4 (exo-isopropyl group) and fimctionality (exo-vinyl group at C-8, enol ether associated with C-6 and C-7) that would allow the straightforward preparation of the tricyclic ring system of ( )-(159). 

A successful formal total synthesis of ( )-quadrone (218) via a route in which a divinylcyclopropane rearrangement played a key role was achieved by employing the substrate (228 Scheme 32). This material is readily prepared from the ketone (227) and, in contrast to compounds (219) and (224), undergoes smooth Cope rearrangement to the tricyclic diene acetal (229), which is easily transformed into the keto acetal (230). A rather lengthy sequence of reactions effects conversion of (230) into the keto aldehyde (221), which, as mentioned previously, has served as an intermediate in a total synthesis of ( )-quadione (218)."... 

The stereocontroiied total synthesis of (+)-gelsemine was accomplished by T. Fukuyama and co-workers using the Knoevenagel condensation to prepare a precursor for the key divinylcyclopropane-cycloheptadiene rearrangement. The use of 4-iodooxindole as the active methylene component allowed the preparation of the (Z)-alkylidene indolinone product as a single stereoisomer. 

The Cope rearrangement of trans- and, notably, cu-l,2-divinylcyclopropanes 1 to 1,4-cyclohep-tadienes 2 (see Section 2.4.5) is a well-known reaction of importance in synthesis. i 11 , i s s. 159... 

This methodology was featured in the synthesis of perhydroazulene sesquiterpenes such as damsinic aid (66) and confertin (67). The rearrangement of divinylcyclopropanes 63 is more effective under combined thermal and photochemical conditions, which also minimizes the competing production of 65. 

A recent synthesis of colchicine (84) featured the divinylcyclopropane rearrangement as a key step. In a model study, cyclopropane 82 in refluxing xylene gave cycloheptadiene 83 in 93% yield. 3... 

A detailed description of the numerous examples of vinylcyclopropropanes used in transition metal mediated organic synthesis is far beyond the scope of this section and can be found in several reviews. Prominent examples are conversions to open-chain products, as well as formation of four-, five-, six- and seven-membered rings via ring expansion or incorporation of other substrates such as carbon monoxide, alkenes or alkynes. Thus divinylcyclopropanes, obtainable via transition metal catalyzed cyclopropanation reactions, undergo a facile thermal Cope rearrangement to form cycloheptadienes. ... 

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