1-oxides’, isomer synthesis

Intramolecular ene reaction. A key step in a new route to anthracyclinoncs such as y-citromycinone (4) is a regioselective intramolecular ene reaction of the unsaturated aldehyde 1 to give 2 in 93% yield. Sharpicss oxidation ((CHOjCOOH, VO(acac), of 2 is regioselective, giving the desired epoxide 3 as the only isomer. Synthesis of 4 is... 

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The pyridine-N-oxide 245 was converted into the cyanopyridine 246 and its isomer (Scheme 80). Grignard reaction, Fischer s indole synthesis, and N-protection gave a pyridinyl indole 247. Selenium dioxide selectively oxidized the methyl group to give the isonicotinic acid. The synthesis of Flavocarpine (244) was finally accomplished by a set of standard reactions as outlined in Scheme 80 (87TL5259). 

The three isomers constituting n-hutenes are 1-hutene, cis-2-hutene, and trans-2-hutene. This gas mixture is usually obtained from the olefinic C4 fraction of catalytic cracking and steam cracking processes after separation of isobutene (Chapter 2). The mixture of isomers may be used directly for reactions that are common for the three isomers and produce the same intermediates and hence the same products. Alternatively, the mixture may be separated into two streams, one constituted of 1-butene and the other of cis-and trans-2-butene mixture. Each stream produces specific chemicals. Approximately 70% of 1-butene is used as a comonomer with ethylene to produce linear low-density polyethylene (LLDPE). Another use of 1-butene is for the synthesis of butylene oxide. The rest is used with the 2-butenes to produce other chemicals. n-Butene could also be isomerized to isobutene. ... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

Construction of the imidazole ring onto a triazine has been also used for the synthesis of this group of compounds. The reaction of 3-aminobenzofl, 2,4]triazine with a-bromoacetaldehyde acetal gave the [1,2-b] linear isomer. On the other hand, the similar reaction on 1-oxide 461... 

When hydrogenolysis of vinylepoxides is used sequentially, it allows for the controlled formation of 1,3-polyols. In the synthesis of the C11-C23 fragment 92 of preswinholide A, hydrogenolysis of ( ) olefin 93 gave the syn isomer 94 (Scheme 9.37) [159]. Methylation, reduction, epoxidation, oxidation, and olefmation of this material then gave vinylepoxide 95, which was subjected to hydrogenolysis to afford 96 in excellent yield. Repetition of this sequence ultimately afforded the desired derivative 94. 

A method for the stereospecific synthesis of thiolane oxides involves the pyrolysis of derivatives of 5-t-butylsulfinylpentene (310), and is based on the thermal decomposition of dialkyl sulfoxides to alkenes and alkanesulfenic acids299 (equation 113). This reversible reaction proceeds by a concerted syn-intramolecular mechanism246,300 and thus facilitates the desired stereospecific synthesis301. The stereoelectronic requirements preclude the formation of the other possible isomer or the six-membered ring thiane oxide (equation 114). Bicyclic thiolane oxides can be prepared similarly from a cyclic alkene301. 

In a more recent and improved approach to cyclopropa-radicicol (228) [ 110], also outlined in Scheme 48, the synthesis was achieved via ynolide 231 which was transformed to the stable cobalt complex 232. RCM of 232 mediated by catalyst C led to cyclization product 233 as a 2 1 mixture of isomers in 57% yield. Oxidative removal of cobalt from this mixture followed by cycloaddition of the resulting cycloalkyne 234 with the cyclic diene 235 led to the benzofused macrolactone 236, which was converted to cyclopropa-radicicol (228). 

The above methodology has been extremely useful for the synthesis of a variety of INOC precursors. For instance, treatment of 0-trimethylsilyl a-bro-moaldoximes 52b, e, f with F ion in presence of unsaturated alcohols 57 produces oximino ethers 58 which can be readily oxidized using NaOCl (Scheme 8) [29]. The transient nitrile oxide intermediates formed undergo spontaneous cyclization to fused isoxazolines 59. The preferred stereoisomer in the formation of the five-membered ring ethers is trans whereas in the six-membered ring ethers the cis isomer predominates (see Table 5). MM2 calculations helped rationalize the experimentally observed stereoselectivites (see Table 5). 

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