Carbene-diene cyclization

Carbene-mediated cyclizations of molybdenum carbene complexes with l,3-nonadien-8-ynes 117 can be induced either by the presence of an electron-withdrawing group on the diene or... 

In the presence of an imidazolium salt and a base, oxidative cyclization of a Ni(0) species upon the diene and an aldehyde takes place first and forms an oxanickellacycle 25, which equilibrates with a seven-membered oxanickella-cycle 26, naturally possessing a cis double bond. cr-Bond metathesis through 26 with hydrosilane affords (Z)-allylsilane (Z)-23. The role of NHC ligand (AT-heterocyclic carbene, generated by H+ elimination from imidazolium C2H by a base) is not clear at present a Ni(0)-NHC complex is believed to effectively produce 26. 

Two type la syntheses of (3-hydroxypyrroles have appeared. An aza-Nazarov cyclization of l-azapenta-l,4-dien-3-ones produced (3-hydroxypyrroles including 2,2 -bipyrroles <06EJO5339>. A second approach to a (3-hydroxypyrrole involved an intramolecular N-H insertion into a rhodium carbene derived from the decomposition of a diazoketone <06JOC5560>. On the other hand, the photochemical decomposition of the diazoketone led to pyrrolidin-2-ones. 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Treatment of enynes 35 and 36 with first generation Grubbs carbene under the above diene ring-closing metathesis conditions did not furnish the desired spiro-cycles. Next, trials of cyclization were attempted by using its imidazolidinylidene... 

Nickel-catalyzed cyclization of a 1,3-diene side chain of the substituted pyrrolidones yields a precursor to the indolizidine alkaloid (—)-elaeokanine C (Equation 86) <1997TL3931>. Other metal-catalyzed reactions include the Rh-induced in situ carbene generation and subsequent cyclization onto the heteroatom to yield piperidines <1997T16565, 1997JOC67>. Pauson-Khand cyclizations have also been used (Equation 87) <1997T6611>. 

In the next step, 3 could insert into one of the C H bonds of 1 to provide vinylacetylene (4, butenyne), a compound that is indeed generated when 1 is pyrolyzed. Repetition of the carbene formation step could then produce 5, which, by another insertion step, would lead to hexa-l,3-dien-5-yne (6, mixture of isomers). This is already an isomer of benzene, and that it can cyclize to 2 was shown by us many years ago [6]. Obviously, 6 could also be a precursor of styrene and other oligomers of 1. The mechanism proposed in Scheme 2 could also be of importance in connection with soot formation from smaller hydrocarbon fragments, and account for the formation of 2 in interfeller space. 

The cyclization of this key intermediate to the fully protected conduritol F derivative 19 showcases the different performance of the standard metathesis catalysts. Despite the excellent track record of the original Grubbs benzylidene carbene complex 2 (7) for the cyclization of 6-membered rings, compound 18 reacts poorly with this particular catalyst in refluxing CH2C12, leading to only 32% conversion after 60h reaction time. This reluctance is likely caused by the preference of diene 18 to adopt a zig-zag-conformation holding the olefin units far apart. 

In line with our previous experiences, diene 56 readily cyclized to the desired 19-membered ring 57 on reaction with the ruthenium carbene 2 (5 mol%) in refluxing CH2C12. The fact that neither the free hydroxyl group nor any other functionality in the substrate interfere with RCM illustrates the excellent compatibility and selectivity of the Grubbs catalyst (7). Hydrogenation of the crude cycloalkene ( -mixture) thus obtained afforded the desired disaccharide 57 in 77% yield. The elaboration of this compound into tricolorin A 46 can be achieved according to literature procedures (25). 

Recently, a catalytic system consisting of a second generation Grubbs catalyst or an in situ non-carbenic ruthenium complex have allowed a cascade catalytic reaction of cyclopropanation/ring closing metathesis of dienynes containing a malonate or bissulfone moiety. In this reaction, the interaction between the triple bond and one double bond gives a bicyclic product via cyclopropanation, and then the subsequent diene RCM produces the last cyclization step [16] (Scheme 6). 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

Reaction of carbonylcarbenes with a triple bond results in either 1,1-cycloaddition product 326 or 1,3-cycloaddition product 327. Substituted furans 327 are also accessible through photolysis, thermolysis, or catalytic rearrangement of carbonylcyclopropenes 326. However, furan formation can be imagined as a cyclization of 6ir-electron system 328, incorporating a singlet carbene or carbenoid center and a conjugated heteroatomic diene... 

Alkenylcyclopropane-l -carbonitriles were obtained in moderate to good yields, in some cases even with good diastereoselectivity, by the photolysis of 3/f-pyrazole-5-carbonitriles in unsaturated solvents (Table 4). On UV irradiation, the pyrazoles isomerize to jS,> -unsaturated a-diazocarbonitriles, which cannot be isolated but decompose rapidly to l-alkenyl(cyano)car-benes, which then either cyclize to cyclopropenecarbonitriles 1 or react with the alkene substrate to give 1 -alkenylcyclopropane-1 -carbonitriles 2. As a rule, the cyclopropanation of electron-rich alkenes, dienes, thiophene, and furan dominates the intramolecular carbene reaction. A generalized procedure can be found in Houben-Weyl, Vol. 19b, p 1209. 

Pentacarbonyl[cyclopropylethynyl(ethoxy)carbene]chromium complex 19 reacted with cyclo-penta-1,3-diene to give a cyclopropyl-substituted carbene complex of norbornadiene 22, which was converted to the corresponding carboxylic acid 23 upon oxidation or to a 1,4-quinone-type derivative 24 after Dotz-type cyclization with phenylethyne. ... 

In fact, the formation of benzene from hexa-l,3-diene-5-yne is possible by at least three different mechanistic pathways (i) at temperatures below 500 - 600°C preferably by an electrocyclization via the isobenzene followed by a 1,3-hydrogen shift, (ii) at temperatures above 500 - 600 °C preferably by the discussed carbene mechanism, and (iii) in the presence of hydrogen radicals by an intramolecular radical cyclization sequence. For further discussion including labelling studies see Nuchter U, Zimmermann G, Francke V, Hopf H (1997) Liebigs Ann/Recueil 1505 and the references cited herein. 

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