Alkenes transformation into enones

A novel Ni(cod)2-catalyzed allene/alkene cyclization has been utilized in the synthesis of (-)-a-kainic acid (Scheme 16.88) [96], A stereocontrolled metallacycle would be generated via coordination of Ni(0) species to both an alkene of the enone and a proximal allenyl double bond followed by oxidative cyclization of the Ni(0) complex. The metallacycle would be transformed into the product through transmetallation of Me2Zn and ensuing reductive elimination. 

Collins reagent is used for the introduction of carbonyl groups at allylic positions." This transformation of alkenes into enones is much slower than the oxidation of alcohols, requiring a great excess of Cr03 2Py and prolonged reaction times. Consequently, alcohols can be oxidized to aldehydes and ketones by Collins reagent without interference from alkenes. 

Most functional groups resist Collins oxidation, including the oxidation-sensitive sulfides106 and thioacetals.103 Although Collins reagent can transform alkenes into enones" and alkynes into inones,107 these reactions are slower than the oxidation of alcohols into aldehydes or ketones. Therefore, alcohols can be usually oxidized with no interference from alkenes108 or alkynes.109... 

PDC is able to oxidize allylic positions, resulting in the transformation of alkenes into enones. This reaction normally demands heating and is best performed in solvents other than CH2CI2.140 Very often, r-butyl hydroperoxide is added.141 When a standard procedure for the oxidation of alcohols with PDC is employed, normally no interference with alkenes occurs. 

We have expanded our collection of stereoselective reactions even more in the making of alkenes by the Wittig reaction (chapter 15), from acetylenes (chapter 16), by thermodynamic control in enone synthesis (chapters 18 and 19) and in sigmatropic rearrangements (chapter 35). We have seen that such E- or Z-alkenes can be transformed into three-dimensional stereochemistry by the Diels-Alder reaction (chapter 17), by electrophilic addition (chapters 23 and 30), by carbene insertion (chapter 30) and by cycloadditions to make four-membered rings (chapters 32 and 33). 

Compound 191 was transformed into the exo-alkene 193 via the respective spiro epoxide the enone 192 (11%) was obtained as a side product (Scheme 24).97 Compound 193 was deprotected, and the triol obtained was selectively mesylated at the allylic position to give, after acetylation, compound 194 (68%). Treatment of 194 with sodium acetate resulted in the inversion of configuration at C-l to give the tetra-N,O-acetyl derivative 195. Oxidation of 195 with osmium tetraoxide in aqueous acetone, followed by acetylation, afforded 196 (87%) and 197 (13%), whose acid hydrolysis provided the free bases 5 and 37, respectively. 

Recently Ahman and Somfai [43] have used an AT-sulfonyl iminium ion-alkene cyclization as a key step in an enantioselective total synthesis of the alkaloid anatoxin A (Scheme 20). a-Hydroxy sulfonamide 55 was prepared from L-pyro-glutamic acid (cf Scheme 12) and was transformed in 6 steps into enone 112. Exposure of 112 to acid led to a mixture of bridged enone 114 and /3-chloro ketone 113. The latter compound could be converted into the desired enone with DBU. Detosylation of 114 provided the natural product (+)-anatoxin A. 

Siloxanes have also been used as temporary tethers to bridge an enone and alkene [70]. Intramolecular [2 + 2] photocycloaddition of 56 provides exclusively straight adduct 57 consistent with the Rule of Five. This product can then be transformed into diol 58 after cleavage of the siloxane tether. (See Scheme 16.)... 

Several other types of domino reactions have been employed in the synthesis of natural products. Diastereoselective conversion of allylic carbonate 173 into enone 174 was one key transformation in a total synthesis of (+)-3-isorauniticine 175 (Scheme 27).Treatment of allylic sulfonamide 173 with a palladium catalyst re-gioselectively forms a 7r-allylpalladium intermediate by carbonate displacement. Carbopalladation of the pendant alkene, carbonylation, a second intramolecular alkene insertion, and /3-hydride elimination delivers a 67 22 11 mixture of stereoisomers of which enone 174 is the major product (isolated in 45-53% yield). Carbopalladation products can also undergo anion capture reactions. For instance, during the synthesis... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

The major compound from this oxidation corresponds to the expected selective oxidation of the allylic alcohol. Minor amounts of compounds are obtained, resulting from 1- an oxidation at an allylic position, resulting in the transformation of an alkene into an enone 2- an oxidation of a lactol in equilibrium with the major hydroxyaldehyde, and 3- a... 

Photochemically induced [2 + 2] cycloaddition is of extraordinary importance in organic synthesis,as this is a method ideally suited for the preparation of sterically congested compounds. The reaction may occur by a concerted mechanism allowed by rules of orbital symmetry, or, more often, via a biradical pathway. For preparative purposes, the most widely exploited is the enone-alkene photochemical [2 + 2] cycloaddition. This reaction proceeds with high regioselectivity, although its stereoselectivity might be low. The first example of the utilization of this reaction for the synthesis of a natural compound, a-cariophyllene 385, was described by Corey (Scheme 2.129). Adduct 386, formed as a mixture of stereoisomers in high yield from simple precursors, was further transformed via the tricyclic intermediate 387 into the... 

One of the most general reaction sequences for the transformation of ketones into alkenes is reduction of the ketone to the corresponding alcohol followed by dehydration. While this method has been widely used, it often suffers from a lack of both stereo- and regio-chemical control in the formation of the double bond. Since the reduction of ketones and the subsequent dehydration of the resultant alcohols are covered in depth in other sections (this volume, Chapter 1.1 and Volume 6, Chapter 5.1), we present here only a few representative examples and divert the reader to these other sections for a detailed analysis of this area. In the total synthesis of (+)-occidentalol (Scheme 4), 1,2-reduction of the enone moiety gave... 

Nucleophilic oxidation of electron-deficient alkenes is another route to epoxides. For example, reaction of enones with hydrogen peroxide and sodium hydroxide provides epoxides in good yield. The first attempt to turn this into an asymmetric transformation utilised the benzylchloride salt of quinine as a chiral phase transfer catalyst but only moderate enantioselectivity was obtained (55% with... 

Avery powerful oxidant, TMDO epoxidizes alkenes up to 10 times faster than the widely used dimethyldioxirane (DMDO), which in turn reacts 10 times faster than a peracid such as perbenzoic acid. The electron-deficient enone C=C bond in anthracycline 59 resists attack by DMDO, but reacts with TMDO to give epoxide 60 in 95% isolated yield. " Naphthalene (61) is transformed by TMDO into dioxide 62... 

Genski and Taylor have employed sucx essfully epoxy-activated alkene 191 for coupling with paraformaldehyde in the presence of EtsAl/BusP to provide the MBH adduct 192, a highly functionalized molecule (containing epoxide and protected alcohol moieties in addition to the p-substituted enone), and transformed the adduct into the bioactive natural product ( )-c/)i-epoxydon (193) (Scheme 2.98). 

When the initial aryl-palladium species has more than one possible proton in the vicinity, the C—H activation can take place several times. Carretero and coworkers [77] observed three C—H activations after the initial Mizoroki-Heck reaction nsing o, /i-nnsatnrated snlfones 134 and iodobenzene. Under normal conditions, the expected Mizoroki-Heck product 135 is formed however, using an excess of iodobenzene, 136 is obtained in high yield. In this transformation, three molecules of iodobenzene are incorporated into the final product. On the other hand, a later study showed that, under the same conditions, similar electron-deficient alkenes as enones do not nndergo this domino reaction instead, only the Mizoroki-Heck product is obtained [78]. A computational analysis of the transformation explained this finding with the difference in the energy of the transition states that ultimately lead to the five-membered ring palladacycle PdCl (Scheme 8.35). 

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