Cyclization selectivity

The barrier to amide rotation is about 16 kcal/mol. It was later demonstrated53 that aryl amides, such as 19, with a somewhat lower barrier to rotation, do rotate more rapidly than they cyclize. Selectivity, then, is governed by electronic and steric factors. 

Synthesis of a m-decalin system by the asymmetric cyclization[38] has been carried out with high enantioselectivity[142,143,147,148], Using BINAP as a chiral ligand, 91% ee was achieved in the asymmetric cyclization of 177 to give 178. In order to achieve an efficient asymmetric cyclization, selection of the reaction conditions is crucial, and sometimes added Ag salts play an important role[148], A catalytic asymmetric cyclization of 179 to prepare the key intermediate enone 180 for vernolepin synthesis has been carried out[149]. Highly efficient asymmetric cyclization of 181 to give the tetralin system 182 has been applied to the synthesis of (-)-eptazocine (183)[150], Hydrindans are synthesized in 86% ee[151]. 

Cyclization selectivities are very different over platinum on silica-alumina than over platinum on silica gel (Table IV). In the case of n-butylbenzene, for example, methylindan/naphthalene ratios differ by about an order of... 

The authors reported that methyl 4-mercapto-2-alkenoates 710, obtained by irradiation of 2(5H)-thiophenones 709 in MeOH, undergo light-induced S-H bond homolysis to give thio radicals 710 (84HCA2198 85HCA2350 87HCA125). Intermediate 710 can be trapped by alkenes to afford 3-thia-hex-5-enyl radical 711, which cyclize selectively to radicals 712, precursors of thiolane-3-acetates 714. 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

The a-amination of aldehydes and subsequent reduction to form oxazolidinones (Scheme 7.6) was developed by the Jorgensen group [7]. In the presence of 10 mol% L-proline as catalyst a variety of aldehydes reacted with azodicarboxylates, 3a and 3a, affording the oxazolidinones 7 after subsequent reduction with borohydride and cyclization. Selected examples of the synthesis of products 7, which were obtained in yields up to 92% and with enantioselectivity up to 95% ee, are shown in Scheme 7.6. 

Direct irradiation of the ester (46) affords isobutyrophcnonc and the cis-cyclobutanol (47) in 35% and 26% yields, respectively. The elimination and cyclization products are the result of Norrish Type II behaviour. However, the selectivity in the cyclization is controlled by the ester function, presumably via hydrogen bonding in the intermediate biradical (48). The ester (49) also cyclizes selectively on irradiation to yield the trans-cyclobutanol (50). 

Iminium ion cycUzations such as the Pictet-Spengler reaction have been widely used in alkaloid chemistry to create a carbon-carbon bond between the carbon a to the basic nitrogen and an aromatic ring. The requisite iminium ions in these reactions are often readily available via the modified Polonov-ski reaction. Although two steps, IV-oxide formation and reaction with trifluoroacetic anhydride, are involved, this approach is often preferable to the reaction of a tertiary amine with mercury(II) acetate, in which it is necessary to destroy the amine-mercury complex at the end of the reaction. In this way the secoheteroyohimbinoidiV-oxide (34) was cyclized selectively to uammigine (35 equation 12). Using mercuiy(II) acetate a nearly equal mixture of (35) and its C-3 P-H epimer tetrahydroalstonine is obtained. 

The ratio of cis trans isomers was 74 26. One obvious interpretation of these results can be derived from observations of Ireland regarding the influence of HMPA on the stereoselection in the formation of ester enolates (7). Based an Ireland s work, in hexane the E-enolate would be formed preferentially and in the presence of HMPA the Z-enolate would be the major diastereomeric intermediate. It follows that E-enolates cyclize selectively to form trans cyclopropanes, and Z-enolates selectively produce cis products (Figure 5). 

Sudhakar and Katz have devised an improved route to [7] helicene. The bromine atom is found to direct the stilbene cyclization away from occupied positions and those ortho to the substituent so that with (153) the bromo [7] helicene (154) is formed in 75% yield on irradiation of benzene solutions containing iodine, and less than 10% of the planar arene (155) is observed. Such results compare very favourably with those from irradiation of the hydrocarbon (156) when equal quantities of the [7] helicene and (157) are formed.Irradiation of (158), the meta isomer of (156), cyclizes selectively without bromine direction and (159) is formed in 75% from xylene solution in the presence of oxygen and iodine The origins of this selectivity may not be readily evident and it is difficult to appreciate why of the four possible conformers of the first intramolecular photo-oxidative cyclization product only (160) undergoes further reaction. The authors suggest that this feature reflects that of the four conformers (160) has the smallest degree of steric interactions between the two aryl moieties. The photo-cyclizations of halostilbenes have been examined by other workers who report that various o-chloro and bromo-compounds (161) undergo... 

The situation with stabilized ylides is rather different from that with unstabilized ones because the formed product has the potential to imdergo Michael addition to the corresponding C-glycoside. It is not clear what factors control the question of cyclization selectivity, but it is certain that reaction conditions and substrate structure both play an important role for the reaction in question. 

Several studies have focussed on the use of chiral esters as auxiliary groups in radical transformations. Perhaps the most comprehensive survey of auxiliary groups was reported by Snider and collaborators in their pioneering examination of Mn(llI)-promoted radical cyclization reactions of fi keto amides and esters [34]. The selectivities obtained in cyclization generally mirror those observed in inter-molecular addition reactions. These examples again illustrate that the models developed for intermolecular radical reactions can apparently be applied successfully to intramolecular additions (cyclizations). Selectivity for the conversion of 34 to 35... 

The cyclization selectivity of 1-hexene to aromatics and naphtenes was measured at low conversion levels of 2-15%. Again AC and CF-1 displayed a similar performance yielding about 70% selectivity and CF-s gave half this value, as illustrated in Figure 3. 

Epoxide 303 has been used an an enantioselective synthesis of the methylenecyclopropa-neacetic acid (514a) portion of (methylenecyclopropyl)acetyl-CoA (514b), a mammalian metabolite of hypoglycines A and B. Addition of the anion derived from phenyl 2-(tri-methylsilyl)ethyl sulfone to 303 produces a 3 1 mixture of threo and erythro diastereomers 509. Either diastereomer cyclizes to the same cyclopropane 511 upon treatment with LDA, which suggests that epimerization at C-5 must be occurring prior to cyclization. Selective removal of the TBPS group followed by oxidation of the alcohol to an acid and elimination affords the desired product 514a (Scheme 73) [126,127]. 

Direct introduction of a C4-bridge is unsuccessful, because upon acylation of y-butyric acid homoannularly cyclization selectively occurs [68], This is why C4- and C 5-bridges have to be constructed by stepwise ring extension reactions... 

HD was inserted stereoselectively by enantiomorphic site control with both catalysts. The cyclization selectivity for 1,5-HD copolymerization was higher than that for 1,7-OD copolymerization. Catalyst 9 gave copolymers with higher cyclization selectivity than catalyst 10 in the propene/1,5-HD copolymerization. 

In none of the complexation experiments were oxocarbenium ions observed. Thus, we were unable to unambiguously correlate the divergent stereochemical results with a change in mechanism. However, it seems certain that the range of cyclization selectivities is a consequence of the various modes of acetal complexation observed. ether the different modes of complexation reflect different mechanisms remained to be established. 

Pingen D, Vogt D (2014) Amino-alcohol cyclization selective synthesis of lactams and cyclic amines from amino-alcohols. Catal Sci Technol 4(l) 47-52... 

Catalyst AgBF4 /MTBD (MTBD = 7-methyl-l,5,7-triazabicyclo[4.4.0]dec-5-ene) Keywords orf/to-AUcynyl acetophenones, carbon dioxide (balloon), silver(l) tetrafluoroborate (AgBF4), MTBD, anhydrous DMF, methyl iodide, room temperature, sequential carboxyl-ation/intramolecular cyclization, selective 5-cxo-oxygen cyclization, 1(37/)-isobenzofuranylidene acetic acids/methyl esters... 

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