Oct-l-en-3-one

The reaction of diethyl dipropargylmalonate (347), with HSiMe2Bu-t catalyzed by Rh2Co2(CO)i2 or Rh(acac)(CO)2 at 50 °C and 15-50 atm of CO affords 2-silylbicyclo[3.3.0]oct-A1,5-en-3-one (348) in excellent yield, which is readily isomerized to bicyclo[3.3.0]oct-l-en-3-one (349) (equation 141). The reactions of other 1,6-diynes including benzyldipropargylamine proceed in the same manner, but a mixture of 348-type and 349-type products is formed in some cases338. 

It was found that by applying the same reaction conditions as for the intermolecular reaction, they were able to obtain moderate yields of bicyclic products (Scheme 2). Starting from hept-l-en-6-yne, they were able to generate the 5,5-ringed bicyclo[3.3.0]oct-l-en-3-one (4). Increasing the carbon tether by one carbon unit and using oct-1-en-7-yne led to the generation... 

Sufficient information about the reaction has been gathered to allow fairly accurate predictions of yield as well as of stereo- and regioselectivity.176177 The reaction proceeds via the formation of hexacarbonylalkyne-dicobalt complexes and is remarkably tolerant of functional groups in both the alkyne and the alkene. The intramolecular Pauson-Khand reaction is an effective way of preparing bi- and polycyclic systems, and the cyclization of 1,6-heptenyne derivatives to give bicyclo[3.3.0]oct-l-en-3-ones has been the most popular application of the Pauson-Khand reaction in natural product synthesis [Eq. (17)]. 

In a sample of defective wines, most in the barrel, half of them contained TCA or TeCA at clearly perceptible doses. Wines may also have defects described as earthy , weedy , wild mushrooms , wet cardboard and considerable research has centred on this. Lee and Simpson (1993) analysed them and identifieds compounds such as 2,4-dichloro-6-methylanisol, chlorated cresols, oct-l-en-3-one, oct-l-en-3-ol, d.y-octa-l,5-dien-3-one, d.y-octa-l,5-dien-3-ol, guayacol, 2-methyl-isoborneol and geosmine. Rapp (1992) also detected other substances in the corks such as 6-chlorovainilline, 4-chloro guayacol, 4,5-dichloro guayacol and veratrol. 

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

Irradiation of the lipid (fet soluble) phase of a meat extract does not produce the characteristic off-odor while irradiation of the aqueous (water soluble) portion of die meat extract results in a typical irradiation odor (20). 3) Irradiation of sulfur-containing amino acids or polypeptides produced a similar off-odor as the irradiation odor (21). 4) The amount of VSCs increased with radiation dose while volatiles from lipids were not always correlated with radiation dose (19). Several earlier researchers suggested that hydrogen sulfide (H2S) and methanethiol (MT) were important for the development of the off-odor (12, 20, 22). Patterson and Stevenson (23), using GC-olfactory analysis, showed that dimethyl trisulfide (DMTS) was the most potent off-odor compound in irradiated raw chicken meats followed by cis-3- and trans-6-nonenals, oct-l-en-3-one and bis(methylthio-)methane. Aim and his colleagues have published extensively on irradiation-induced volatile compounds in raw meats (11). They have identified MT, dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and DMTS in different types of irradiated raw meats using GC-FID and GC-MS. 

Enynes in which three or four atoms separate the double and triple bonds cyclize upon complexation to Co2(CO)g and subsequent heating to give bicyclic enones (equation 52). With the exception of slightly elevated temperatures the conditions required are no different than those of the stoichiometric procedure described earlier for reactive substrates in intermolecular Pauson-Khand reactions. The intramolecular cycloaddition cannot in general be carried out under catalytic conditions. Hex-l-en-5-yne, which would give a four-membered ring upon intramolecular cycloaddition, instead undergoes alkyne trimerization exclusively.3 The most extensively studied systems are those derived from hept-l-en-6-yne, as the products, bicyclo[3.3.0]oct-l-en-3-ones, are useful in the synthesis of numerous cyclopentane-based polycy-clics. 

Several other examples of stereoselective synthesis of polycyclic ketones, via carbonylative [2 + 2 + 1] cycloaddition of organopalladium compounds derived from norbornene and norbor-nadiene, have been reported53,54,121. These reactions are useful in the synthesis of cyclopen-tanoid compounds, such as dihydrojasmone54 The nickel-catalyzed version of this method was used in a total synthesis of methylenomycin B55 and in the stereoselective synthesis of bicy-clo[3.3.0]oct-l-en-3-one derivatives56. Thus, (E)- or (Z)-9-bromo-l-methoxy-7-nonen-2-yne (5), upon intramolecular carbonylative cyclization promoted by tetracarbonyl nickel, afford the same stereoisomer of methyl 1,2,4,5.6,6a-hexahydro-3-methoxymethyl-2-oxo-l-pentaleneac-etate (6) in 43-50% yield with a relative trans configuration of the H-l and H-6a protons. 

Tethering the ene and yne reaction partners for Pauson-Khand cycloaddition was first conceived as a way to improve simultaneously the effective reactivity of simple alkene moieties and to provide access to a wider variety of bi- and polycyclic systems. Indeed, well over 100 examples of such cycloadditions have been published, mostly involving reactions of derivatives of 1,6-heptenyne to give bicyclo[3.3.0]oct-l-en-3-ones [cf. Eq. (37)] together with a smaller number of 1,7-octenynes, which afford bicyclo[4.3.0]non-l (9)-en-8-ones [81 c, 117]. The use of dry-state conditions [118] or additives such as amine oxides [119] has virtually revolutionized this field the cycloaddition shown in Eq. (52) is completed in 15 minutes( ) when promoted by NMO. 

Most applications of this chemistry have utilized more highly substituted and functionalized systems, for which intramolecular cycloaddition rates and yields are significantly better than in the original prototypical examples. Only substitution at the olefinic C-atoms is generally detrimental to the success of the reaction. For example, while 1,6-heptenyne cyclizes to give only 31% of bicyclo[3.3.0]oct-l-en-3-one after four days at 95°C, substrates with C4 disubstitution typically proceed to product in much less time with yields at least twice as high ( gm-dialkyl effect ). Using either dry-state conditions or amine oxide promoters, 55-95% yields are routinely obtained after hours or in some cases even minutes. 

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