Cyclopen tenones reactions

A similar trend was observed in the reaction of tri- and tetrasubstituted etiolates derived from 2-unsubstituted or 2-bromo substituted 3,4-dihydro-6-methoxy-1(2//)-naphthalenone16. The trisubstituted cnolate underwent addition to (—)-(2 )-2-(4-methylphenylsulfinyl)-2-cyclopen-tenone via attack on the nonchelated conformation to give an adduct of d.r. [(2S)/(2/ )] 77 23. The tetrasubstituted enolate underwent addition to the corresponding ( + )-(5)-enone via attack on the chelated conformation to give an adduct with the same absolute configuration at C-2 but with d.r. [(2R) (2S)] 95.5-97 4.5-3. 

The reaction of 1,3-diamino-1,3-dienes with aryl or a,/J-disubstituted alkenylcarbene complexes leads to the formation of formal [4S+1C] cyclopen-tenones [25a] (Scheme 35). In the case of alkenylcarbene complexes, the substitution of the double bond of the complex in both a- and /J-carbons seems to play a fundamental role as reactions performed in the same conditions but using alkenylcarbene complexes with other substitution patterns leads to compounds of a different nature ([4+3], [4+2] and [2+1] cycloadducts). 

As described previously, the Co-mediated carbonylahve Co-cydization of an alkyne and an alkene, is a very powerful procedure in the preparation of cyclopen-tenones [268], However, depending on the reaction conditions it also allows the preparation of 1,3-dienes, which may be intercepted by a Diels-Alder reaction, as described by Carretero and coworkers [285]. As expected, reaction of 6/4-28 with Co2(CO)8 in refluxing acetonitrile led exclusively to the diastereomeric cyclopen-tenones 6/4-29 and 6/4-30 as a 59 41 mixture. However, using trimethylamine-N-... 

A very new example for the combination of an Au -catalyzed [3,3]-rearrangement and a Nazarov reaction has been disclosed by Zhang and coworker. Thus, cyclopen-tenones could be easily achieved by converting en-ynyl acetates in the presence of AuCl(PPh3)/AgSbF6 [320]. 

The Pauson-Khand reaction (PKR) [96] consists of the synthesis of cyclopen-tenones by reaction of an alkene with a dicobalthexacarbonyl complexed alkyne (Scheme 57) and has recently emerged as one of the methods of choice for the obtainment of five-membered carbocyclic rings [97]. Its unique atom connectivity, which involves the two unsaturated carbons of the reagents and the carbon atom of a carbon monoxide ligand of cobalt usually in a regioselective manner (Scheme 57), has brought to refer to PKR as a [2 -I- 2 + 1] cycloaddition. 

Co2(CO)6 fragments at the C=C triple bonds further from the Pt center. The Pauson-Khand reaction between tra 5-Pt C=CC2H[Co2(CO)6] (PR3)2 (R = Et, Bu) (197) and norbomene or cyclopentene gives the corresponding cyclopen-tenones 198 (Scheme 44). ... 

This strategy culminated in the synthesis of the racemic tricycle 282 as a pair of diastereomers that were separated by chromatography. The cyclopen-tenone 274 served as A-ring building block and the C-ring was synthesized utilizing a Diels-Alder reaction between 279 and 280 as the key step. 

A formal 13+2 -cycloaddi lion can be accomplished by adding bis(2-carbethoxyethyl) zinc to acetylenic esters . This reaction allows the construction of complex cyclopen-tenones, such as 388, which is a precursor of ( )-bilobalide (Scheme 101) . The allylzincation of tiimethylsilylacetylenes can be performed intramolecularly providing a functionalized alkenylzinc which cyclizes in the presence of Pd(PPh3)4 at 25 "C within 3.5 h, leading to the bicyclic product 389 in 84% yield (Scheme 102). The addition of allylic zinc halides to various alkynes occurs in the absence of copper salts. The related... 

Alkyne-alkene carbonylative coupling. Intramolecular carbonylative coupling of dialkynes catalyzed by Fe(CO)3 provides a route to cyclopentadienones (equation I). The more difficult carbonylative alkyne-alkene coupling to provide cyclopen-tenones (Pauson-Khand reaction) can also be effected with Fe(CO)s, but in modest yield. In an improved coupling, acetone is treated with Fe2(CO)9 to form Fe-... 

With the exception of propynoic acid derivatives, all alkynes undergo the reaction. On the other hand, generally, only strained olefins react efficiently in the intermolecular PKR whereas electron deficient alkenes give the reaction only in limited examples. With respect to regioselectivity, the bulkier substituent of the alkyne is placed adjacent to the carbonyl in the cyclopen-tenone product. Unsymmetrical olefins usually give mixtures of regioisomers... 

Finally, a Nicholas-type reaction is presumably responsible for an unexpected result reported by Alcaide. During their work devoted to the application of the PKR in the field of -lactams and azetidines they reacted complexed azetidine 91 with TMANO, isolating a mixture of the expected PK product 92 and by-product 93. The formation of 93 is believed to be a consequence of the ionization of the propargylic C - N bond at the cobalt-acycle step. The crowded metallacycle formed after the insertion of the olefin (93), would prompt the cleavage of the C - N bond, forming an ionic species (94) that would trap a hydride, possibly from a cobalt hydride giving 95, which then would follow the usual pathway towards the cyclopen-tenone (Scheme 27) [124],... 

Kirmse and Streu have used the photocycloaddition of ethene to cyclopen-tenone and 3-methylcyclopentenone to yield the [2 + 2] adducts (32, R = H or Me) as a route to the synthesis of the norbornenones (33). Cyano Dewar heptalene (34) has been successfuUy synthesized using a multi-stage reaction in which the photocycloaddition of ethyne to the enone (35), yielding (36), played an important part. The Dewar heptalene (34) is photochemically labile and is converted into (37) on irradiation with 254 nm light, although it is... 

Lithium /i-butylborohydride is prepared by reacting equimolar amounts of n-butyl lithium and bo-rane dimethyl sulfide complex.This reagent effectively reduces enones in toluene-hexane mixtures at -78 °C to give, in most cases, high yields of the corresponding allylic alcohols.Conjugated cyclopen-tenones, however, give mixtures of 1,2- and 1,4-reduction products. Under identical reaction conditions, saturated ketones are reduced to alcohols. The latter process can take place in the presence of simple esters. 

Since many furans are not particularly sensitive to light they often form as products of photochemical reactions. A high pressure mercury arc can be used to eject nitrogen from pyridazine Ai-oxides and form cyclopropenyl ketones and their furan isomers.29 High yields of 2-acetylfuran can be achieved by irradiating the pyrilium ion in Scheme 5 (i.e., the requisite pyrone dissolved in sulfuric acid) although the conditions, mainly the acidity, have to be carefully controlled.30 Surprisingly, the intermediate cyclopen-tenone diol can be isolated with 50% sulfuric acid it is converted to the furan in a separate step. 

Several examples of intramolecular dicarbonylative addition of 1-alkenyl halides to double bonds are reported to give cyclopen tenones, cyclohexenones, or other carbocyclic ketones with additional carboxylic ester functions in the side chains. These reactions can either be catalyzed by palladium(II) catalysts26-28 or by tctracarbonylnickel29. 

These nucleophilic carbenes afford only poor yields of the expected cyclopropane derivatives when 2-cyclohexenone or 1-nitrocyclohexene is used as the electron-deficient olefin. On the other hand, reaction of the cyclopropene with diene esters provides [4 -I- 2] cycloadducts, and reaction with alkenes possessing two geminal electron-withdrawing groups gives cyclopen-tenone derivatives via a [3 + 2] cycloaddition8. 

Scheme 4-25 summarizes the most common metal-promoted /nfe/molecular cyclocoupling reactions of various species with alkynes. The most prominent organic products include arenes, cyclooctatetraenes, cyclohexadienes (with olefins), pyridines (with nitriles), cyclopen-tenones (with olefin ( CO the Pauson-Khand reaction [98]), pyrones (with CO2), and five-membered heterocycles (with X = S, Se) common organometallic products include cyclobutadiene complexes, cyclopentadienone complexes, and metallacyclopentadienes. 

Motoyoshiya et al. in the course of their studies on the Nazarov reaction [19] found a convenient method for the synthesis of 1, whose substituted cyclopen-tenone ring with the exocyclic a-methylene group was constructed in one operation [20]. This synthesis began with the acylation of dimethyl methanephos-phonate 9 with tigloyl chloride to produce the unsaturated jS-ketophosphonate 10 which in the next step was reacted with aqueous formaldehyde to give the dienone 11. The Nazarov reaction of the latter provided methylenomycin B (1) in 12% overall yield (Scheme 5). 

Several syntheses of aldehydes and ketones based on the insertion of carbon monoxide have been reported. Reaction of norbornadiene with monosubstituted acetylenes in the presence of octacarbonyldicobalt gives the fused cyclopen-tenone (35) in high yield conjugate addition of a cuprate and vacuum pyrolysis completes a simple synthesis of 2,3-disubstituted cyclopent-4-enones (36) (Scheme 30)." Conjugated dienes with methyl iodide in the presence of the same cobalt reagent yield conjugated dienones (37) [equation (8)]." In a review of carbonyl insertion reactions, the same reagent is reported to catalyse the reaction... 

Finally, the involvement of deoxy-Breslow species as intermediates and related to the reactivity profile of acrylates under NHC catalysis has been reported twice. The first report dealt with detailed mechanistic studies of the well-known tail-to-tail dimerization of methyl acrylate. By means of complementary and robust experiments (including kinetic isotope effects, deuterium-labelling studies and competitive reactions), the formation of the dimer (148) has been unambiguously rationalized. The second report has described/or the first time the NHC-catalysed cyclotetramerization of acrylates. Using imidazolium chloride (135) as NHC source, various trisubstituted cyclopen-tenones (149), thus resulting from the cyclotetramerization of acrylates, have been obtained in moderate yields. 

Another cobalt-mediated cyclization reaction is the Pauson Khand reaction (PKR). In a [2 -H 2 - - 1] fashion, the reaction of TMSA with alkenes delivers regioselectively silylated cyclopen-tenones. Following the trend typically observed in the PKR, the bulky TMS-group is always positioned a to the carbonyl group (eqs 37 and 38)7 ... 

Reaction with Allylic and Benzylic Electrophiles. The acyl radicals can be trapped with halogen- and silicon-based electrophiles. a -Allylation of a, -unsaturated ketones is done while using Mn(OAc)3 dihydrate and allyl bromide in refluxing benzene (eq 29). Better yields are usually observed for cyclopen-tenones compared to cyclohexenones. a -Benzylation is also possible using benzyl bromide as the electrophilic partner (eq 30). Both methods tolerate a range of substitution, including 8-alkoxy-a, -unsaturated ketones. It is possible to perform a sequential allylation/cyclization with an excess of allyltrimethylsilane (eq 31). Mn(OAc)3 offers good conversions, but the use of ceric ammonium nitrate (CAN) as co-oxidant improves yields. 

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