Enediynes cycloaddition

Enediynes 38 undergo [2+2+2] cycloaddition reactions to afford polycyclic cyclohexadienes 39 in presence of a cobalt catalyst (Scheme 5.11) [14]- In this system, the presence of a NHC ligand improved the catalytic power of cobalt when compared with phosphine ligands. In addition to increased yields, lower ligand... 

Scheme 5.11 [2+2+2] Cycloaddition reactions of enediynes in presence of a NHC-Co complex...

Bicyclic cis- and frans-isoxazolidinyldiynes have been prepared by intramolecular nitrone cycloaddition of the two side chains of an acyclic enediyne-nitrone precursor (Scheme 2.233) (731). 

Intramolecular [2 + 2 + 2] cycloadditions belong to the same type of valence isomerization as those of 1,5-unsaturated compounds to cyclobutanes.70 The cobalt-mediated cyclization of l-en-5-ynes stereoselectively converts enediynes directly to bicyclo[4.2.0]hexa-l,3-dienes, as single diastereomers, when a stoichiometric amount of dicarbonyl(cyclopentadienyl)cobalt is used. This cyclization90 has a high efficiency (92%). An example is the synthesis of the protoilludane framework 23 from the enediyne precursor 22.71... 

Cycloaddition of cncdiynes. Photolysis of the enediyne 1 in the presence of catalytic quantities of CpCo(CO)2 in refluxing toluene results in the tricyclic diene 2. The reaction involves a diene rearrangement in the expected product (a).1... 

Cycloaddition to a hydrocyclobutaindane.1 The framework of the sesquiterpenoid illudol (3) can be obtained in one step and high yield by a [2 + 2 + 2] cycloaddition of the acyclic enediyne 1 mediated by CpCo(CO)2. Transformation of 2 to 3 involves a number of standard reactions. The cycloaddition of 1 to 2 is the first instance of formation of three rings in a single step and with stereospecific generation of three contiguous chiral centers. 

Several groups have developed the combination two or more PKR or PK-type reactions in the same reaction step. The multiplication of the synthetic power of this transformation has found immediate application for the synthesis of natural [S.5.5.5] systems called fenestranes. Starting materials have been enediynes that give two [2 + 2 + 1] cycloadditions. The extension of the reaction to triynes has led to interesting tandem processes that may include [2 + 2 + 2] cyclizations. Other cycloadditions like the Diels-Alder have also been combined with the PK. 

Estrones. An A —> BCD approach to estrones involves a cobalt catalyzed intramolecular 2 + 2 -y 2] cycloaddition of the enediyne 1 to form the B, C. and D rings in one step. The high stereoselectivity suggests that the cyclization involves a Dicls-Alder-type reaction of the vinyl group with a cobaltacyclopentadiene formed by coupling of the two alkyne units. The homoannular diene obtained on demetalation is isomcrized easily to the diene 3. 

Malaciia and co-workers reported an improved diastereoselectivity of the Cocatalyzed cycloaddition of substituted linear enediynes by introducing substituents such as esters, sulfoxide, or phosphine oxide at the terminal position of either the double or the triple bond [76]. 

With an appropriate precursor C-ring, dienyl steroids have been made accessible in a remarkably highly stereoselective process [77]. Intramolecular cycloaddition reactions of enediynes containing a terminal alkyne group have also been observed by Vollhardt [78] (eq. (27)). 

Slowinski, R, Aubert, C.. and Malacria, M., Highly stereoselective induction in the cobalt-mediated [2 -I- 2 -I- 2] cycloaddition of chhal phosphine oxides substituted linear enediynes. Tetrahedron Lett., 40, 5849, 1999. 

Scheme 77. Intramolecluar, metal-mediated [2 + 2 + 2] cycloaddition of an enediyne to form polycycles of medical interest.

The bisiodonium ethyne 30 is even more reactive than 11 and undergoes Diels-Alder cycloaddition [24] with cyclopentadiene and furans in a matter of minutes at low temperatures (Scheme 3-10). The structure of adduct 122 was unambiguously established by X-ray analysis [24]. Cycloadducts 122 and 123 can be reacted with RC = CLi to give enediynes, 125, or with nucleophiles [90] to give 126 (Scheme 3-10). 

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