Bicyclo octan-2-ones reactions

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

In an approach to the AB rings of rubrolone 65, Boger examined the use of oxazinones as a replacement for triazines. Reaction of l,3-oxazin-6-one 66 with enamines 67 produced the corresponding pyridines 70. The reaction proceeds in a manner analogous to the triazines however, instead of losing nitrogen, these systems lose CO2 via the intermediate bicyclo[2.2.2]octanes 68. The resultant 69 then loses pyrrolidine as in the triazine example. 

The Michael addition followed by Intramolecular Ring Closure (MIRC) reactions have been recognized as a general synthetic approach to carbocyclic three-membered ring derivatives [1]. The enhanced Michael reactivity of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) towards thiolates, alkoxides, lithiated amides and cyclohexadienolates (see below) allows one to perform highly efficient assemblies of spiropentane, tricyclo [3.2.1.0 ]octane, bicyclo [2.2.2] octane... 

Further evidence for the intermediacy of 4-hydroxycyclopent-2-en-l-ones (1 1 adducts) in the Weiss reaction of 1,2-dicarbonyl compounds It1 COCOR2 with dimethyl 3-oxoglutarate (MeC CCHk CO, to give cA-bicyclo [3.3.0] octane tetraesters, has been reported and steric effects on the condensation have been explored.39... 

Bicyclo[2.2.1]heptane (norbomane) and bicyclo[2.2.2]octane, when treated with nitronium tetrafluoroborate in nitrile-free nitroethane, unexpectedly gave no nitro products. Instead, only bicyclo[2.2.1]heptane-2-one and bicyclo[2.2.2]octan-l-ol were isolated, respectively.500 Observation of bicyclo[2.2.1]heptane-2-yl nitrite as an intermediate and additional information led to the suggestion of the mechanism depicted in Scheme 5.48. In the transformation of norbomane the first intermediates are the 2-norbornyl cation 126 formed by hydride abstraction and nonclassical cation 127 formed through insertion of N02+ into the secondary C—H bond. In the case of bicyclo [2.2.2]octane, the oxidation of bridgehead tertiary C—H bond takes place and no further transformation can occur under the reaction conditions. Again these electrophilic oxygenation reactions testify to the ambident character of the nitronium ion. 

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

The external bonds in bicyclo[4.2.0]octan-2-ones can be cleaved both by reductive and oxidative processes, both reactions affording disubstituted cyclohexanones. This is illustrated (Sch. 18) by the SmI2-promoted formation of 3-alkyl-3-ethylcyclohexanones 69 from 6-alkylbicyclo[4.2.0]-octan-2-ones 70 [73], and by the formation of 2-alkyl-3-acylcyclohexanones 71 from 7-trimethylsilyloxybicyclo[4.2.0]octan-2-ones 72 via single electron oxidation [74]. 

The reaction of homochiral allylsilanes with a-enones and a-enals is very valuable for the asymmetric synthesis of multisubstituted cyclopentanes (Equation (40)).161,162 The [3 + 2]-cycloaddition of allylsilanes is applicable to />-quinones163 and />-quinoneimines.164 3-Butyn-2-one undergoes a double cycloaddition with an excess amount of allyltriisopropylsilane to give a bicyclo[3.3.0]octane in good yield (Equation (41)).165... 

The role of acid-catalyzed reactions in bicyclo[3.3.0]octane synthesis has also been a major one. It is now well established that 6-lactones (e. g., 14)41 and certain 7-lactones (7J)42) undergo dehydrative cyclization when heated with polyphosphoric... 

Examples are known of photoextrusion reactions which occur with ring contraction and provide bicyclo[3.3.0]octane derivatives. 1,2-Quinone diazides (e. g., 225)189 190) and bicyclo[3.3.1]nonan-9-ones (e. g., 126)191,192) are particularly... 

The oxa-thiacrown ether having bicyclo[2.2.2]octane units was prepared from a mixture of dichloro sulfides 28 and 29 <2002CHE261>. The reaction of the mixture with diethylene glycol by a high-dilution method led to the formation of only one stereoisomer of 30 in 40% yield (Scheme 3). 

DCP as a Chiral Controller in Oxidative Free Radical Cyclizations. As a chiral auxiliary, DCP (1) is also reported to induce modest diastereoselection (60% de) in Mn(III)-based oxidative free-radical cyclizations of p-keto esters (eq 12). Chiral p-keto ester 25 was prepared by transesterification reaction with methyl ester 23, 1, and 0.3 equiv of DMAP (catalyst) in anhydrous toluene at reflux for 3-5 d as described by Taber. Oxidative cyclization of a 0.1 M solution of 24 in AcOH with 2 equiv of Mn(OAc)3-2HzO and 1 equiv of Cu(OAc)3 HzO provided bicyclo[3.2.1]octan-2-one (25). 

Bicyclic ketones are prepared by cycloadditions of methylenecyclopropanes with cyclic a,P-unsatu-rated carbonyl compounds. c J-Bicyclo[3.3.0]octan-2-ones (50), (51) and (52) are obtained in good yields by phosphine-nickel(0)-catalyzed cross coupling reactions of 2-cyclopentenone with methylenecyclopropanes in the presence of 0.1-1 equiv. of triethylborane as a Lewis acid (equations 18 and 19 and... 

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