Cycloaddition oxidation step

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

The formation of compound (16) is proposed to proceed through the nitrile oxide (15) as an intermediate to undergo intramolecular nitrile oxide-olefin cycloaddition (INOC). On the contrary, the generation of (18) is proposed to proceed through intramolecular alkoxycarbonyl nitronate-olehn cycloaddition (lAOC) step because only the trans isomers are formed. 

Entry 3, Scheme 10.26) [52]. However, the use of an enantiopure mthenium salen complex (19) did not generate asymmetric induction, which suggests that the acyl nitroso dienophile intermediate readily dissociates from the chiral mthenium complex involved in the oxidation step prior to Diels-Alder cycloaddition. 

An example of a third-generation cycloadduct 187 was synthesized via alternating 1,3-dipolar cycloaddition and oxidation steps starting from 3,4-dihydro-2//-pyrrole 1-oxide and furan-2(5//)-one (Scheme 44) <1997T2979>. 

Moreover, all cycloaddition pathways require an oxidation step to recover the flavylium moiety within the final structures, as well as direct reactions yielding A+-F species. In fact, it has been shown that direct reactions may lead to either A(-0-)F product or A+-F pigment from the same flavene intermediate. The former was detected only in wines carefully protected from oxygen exposure... 

The starting point is the alkoxy-bound oxo metal derivative of a (Z,Z,Z)-triene 4. Intramolecular [2h-2] cycloaddition affords a metallaoxetane 5, [8] and the first tetrahydrofuran ring is then closed by reductive elimination of the metal to form compound 6. An oxidation step from 6 to 7 activates the alkoxy bound metal for the next [2-h2] cycloaddition (7 8). Reductive elimination of the metal... 

The synthesis of the synthons for the A and C ring of the natural product and the preparation of the substrate for the crucial oxidative dearomatization/intramolecular [4+2] cycloaddition key step are shown in Scheme 12.44. 

Scheme 11.18) [39]. The five-step sequence (cycloaddition, oxidation, ester hydrolysis, carbonyl deprotection, decarboxylation) required for the transformation of chromium carbene chelate 50 into the benzyl-protected rolipram precursor has been performed tvithout isolation of any intermediates after the final debenzyla-tion (-I-)-rolipram 51 is obtained in lotv overall yield. 

Unexpectedly, a completely different reaction took place in the oxidation of 2-(l-propenyl)phenol (111) with PdCh. Carpanone (112) was obtained in one step in 62% crude yield. This remarkable reaction is explained by the formation of o-quinone, followed by the radical coupling of the side-chain. Then the intramolecular cycloaddition takes place to form carpanone[131]. 

Pasinszki and Westwood investigated the dimerization of chloronitrile oxide CICNO to 3,4-dichloro-l,2,5-oxadiazole-2-oxide 78 (Scheme 48) [98JPC(A) 4939]. From B3-LYP/6-31G calculations, they conclude that the reaction path can be characterized as a typical Firestone-type cycloaddition, a two-step mechanism with a C—C bond forming characterizing the first reaction step. The activation... 

A two-step sequence of nitrile oxide-olehn cycloaddition and reduction of the resulting A -isoxazolines offers a unique and attractive alternative to the classical aldol reaction and its many variants (2J). The procedure bypasses traditional problems, including enolate equilibrium and cross condensation (20). 

As formal a, /i-unsaturated sulfones and sulfoxides, respectively, both thiirene dioxides (19) and thiirene oxides (18) should be capable, in principle, of undergoing cycloaddition reactions with either electron-rich olefins or serving as electrophilic dipolarophiles in 2 + 3 cycloadditions. The ultimate products in such cycloadditions are expected to be a consequence of rearrangements of the initially formed cycloadducts, and/or loss of sulfur dioxide (or sulfur monoxide) following the cycloaddition step, depending on the particular reaction conditions. The relative ease of the cycloaddition should provide some indication concerning the extent of the aromaticity in these systems2. 

Vinyl- and acetylenic tricarbonyl compounds are reactive dienophilic components in Diels-Alder reactions. Cycloadditions of these compounds with substituted butadienes were recently used to develop a new synthetic approach to indole derivatives [14] (Scheme 2.9) by a three-step procedure including (i) condensation with primary amines, (ii) dehydration and (iii) DDQ oxidation. 

Diels-Alder reaction of the furan derivative 148 with homochiral bicyclic enone 149 is the key step [56] in the total synthesis of the diterpenes jatropho-lone A and B, 151 and 152, respectively, isolated from Jatropha gossypiifolia L [57], Initial efforts to carry out the cycloaddition between 148 and 149 under thermal or Lewis-acid conditions failed due to diene instability. Application of 5kbar of pressure to a neat 1 1 mixture of diene and dienophile afforded crystalline 150 with the desired regiochemistry (Scheme 5.23). Subsequent aromatization, introduction of the methylene group, oxidation and methylation afforded (-l-)-jatropholones 151 and 152. 

Although nitrile oxide cycloadditions have been extensively investigated, cycloadditions of silyl nitronates, synthetic equivalent of nitrile oxides in their reactions with olefins, have not received similar attention. Since we found that the initial cycloadducts, hl-silyloxyisoxazolidines, are formed with high degree of stereoselectivity and can be easily transformed into isoxazolines upon treatment with acid or TBAF, intramolecular silylnitronate-olefin cycloadditions (ISOC) have emerged as a superior alternative to their corresponding INOC reactions [43]. Furthermore, adaptability of ISOC reactions to one-pot tandem sequences involving 1,4-addition and ISOC as the key steps has recently been demonstrated [44]. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

The synthesis in Scheme 13.64 was carried out by E. Carreira and co-workers at ETH in Zurich, Switzerland. A key step in the synthesis in Scheme 13.64 is a stereoselective cycloaddition using a phosphonyl-substituted nitrile oxide, which was used to form the C(16)-C(17) bond and install the C(15) oxygen. 

The C(6)-C(15) segment was synthesized by Steps C-l and C-2. The stereoselectivity of the cycloaddition reaction between the nitrile oxide and allylic alcohol is the result of a chelated TS involving the Mg alkoxide.39... 

A potentially useful approach to the marine alkaloid papuamine based on INOC strategy is proposed as shown in Scheme 8.21. In fact, a tnms-hydrindane intermediate has been synthesized in racemic form using a model sequence of reactions involving a nitrile oxide cycloaddition as a key step (Eq. 8.69).106... 

Langlois synthesized (lS,5R)-44 by employing [3+2] cycloaddition between methyl methacrylate and camphor-derived oxazoline N-oxide (A) as the key-step (Scheme 66) [98]. 

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