Imines thioketones

The following reactions proceed with the participation of the allylic boron system (i) allylboration and protolytic cleavage of organic compounds with multiple bonds, (ii) allylboron-alkyne condensation,598 599 (iii) reductive mono-and trans-a,a -diallylation of nitrogen aromatic compounds, (iv) disproportionation processes between tribut-2-enylborane and BX3 (X = C1, Br, OR, SR). Allylboration of carbonyl compounds, thioketones, imines, or nitriles leads to the homoallylic alcohols, thiols, or amines (Equations (136) and (137). It is most important that 1,2-addition to aldehydes and imines proceeds with high diastereoselectivity so that ( )-allylic boranes and boronates give the anti-products, while -products are formed preferentially from (Z)-isomers. 

There is almost no restriction in the choice of an appropriate electrophile in the Knoevenagel reaction. Aldehydes, ketones, thioketones, imines, enamines, acetals and orthoesters have been used. With less reactive methylene groups, however, drastic reaction conditions may be necessary. Steric effects have a significant influence on the rate and unexpected compounds are often obtained as a result of secondary reactions. Reaction of 1,3-dicarbonyl compounds with carbon disulfide followed by dialkylation with an alkyl halide give diacylketene-S,5-acetals (159). However, even with highly acidic dicarbonyl com-... 

Hetero-Diels-Alder reactions performed with trifluoromethyl-substituted heterodienes or with trifluoromethyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imines, nitriles, and their parent x./J-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and. depending on the partners, with [2+ 2]-cycloaddition reactions. 

Raasch, and Schaumann and co-workers, have studied the reactions of bis (trifluoromethyl)thioketene (83 R1 = CF3) with alkenes, with thioketones, and with carbodiimides or Schiff-base imines. The products were, respectively, thietans, 1,3-dithietans (84 R1 = CF3), and 1,3-thiazetidines (85 R1 = CF3) (from the carbodiimide).114,115 With phenyl azide the 1,2,3,4-thiatriazoline (86 R = CF3) is formed subsequent pyrolysis yields2,l-benzisothiazole.114... 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

N-benzyladamantyl-2-imines, and 2-methyleneadamantanes were studied (352, 353). In particular, X-ray single-crystal analysis confirmed the configuration of the oxathiazoline 185, resulting from the favored attack of nitrile oxide on the 5-fluoroadamantane-2-thione. 2-Silyl-substituted oxathiazole 186 was synthesized by the 1,3-dipolar cycloaddition reaction of phenyl triphenylsilyl thioketone with 4-chlorobenzonitrile oxide (354). 

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

Di-t-butvl ketone imine (5.64 g) in dry light petroleum under dry nitrogen was treated with ethereal methyllithium (1.00 mol. eq). When methane evolution had ceased, dry carbon disulfide (3.2 ml) was added and the mixture stirred for 3h. The solvent was removed under reduced pressure at room temperature and the solid brown residue heated at 80-100°C under vacuum, and practically pure thione was distilled into a solid C02-acctonc trap (100%). The residue is yellow when the distillation is complete. Redistillation afforded the pure, deep-violet, thioketone, b.p. 61°C/14 torr. 

We have already mentioned the synthetic versatility of silyl thioketones249 which is confirmed because they react with 1,3-dipoles (nitrile oxides, nitrile imines and nitrile ylides) to give regiospecifically silyl thiaheterocycles462. Equation 135 illustrates the reaction between phenyl trimethylsilyl thioketone and diphenyl nitrihmine. 

Regiospecific addition took place affording good yields of thietanes 143503 and, with alkynes, diene systems were formed504. Fischer has also described the reactions of thioketones with (CO)sW=NPh which undergo metathesis with these substrates to yield N-phenyl imines 144505 as shown in equation 154. 

But the more heteroatoms, the more alternatives. We could disconnect the enamine first 27a and the C-S bond second 31. This suggests a reasonable a-halo-ketone 33 and an unstable-looking imine 32. Fortunately this is just a tautomer of the thioamide 34. Though thioketones are unstable, thio-amides are stable thanks to extra conjugation. 

Other thermal 1,3-dipolar cycloadditions are the reactions between nitrile sulfides and electron-deficient aldehydes and ketones forming 1,3,4-oxathiazolines (98 Scheme 19) between aryl thioketones and thiofluorenone 5-tosylimide to yield the 1,3,4-dithiazolidines (204) and between thioketene S-oxides and imines, yielding in one case the 1,2,4-oxathiazolidine (136). 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

The addition of ZnBr2 to the tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones7 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material. The cycloaddition of thiophene-2-carhaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, suhstituted isoxazolidines, and not the previously reported 4 - - 2-adducts. Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines. The 3 -h 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-1,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22). The first imequivocal 1,3-dipolar cycloaddition of sulfines involves the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide with diaryl thioketones to produce... 

If we put two of these functions on the same carbon, in principle, one may be able to produce a maximum of two C-C bonds in reactions with appropriate carbon nucleophiles. Which functions are these Acetals, thioacetals, aminals, a-dihalidcs, and so on. Then, all of them should be FN = 2 groups. This analogy continues with triheterosubstituted (FN = 3) and tetraheterosubstituted (FN = 4) carbon functions. Unsaturated systems are also classifiable in these terms. Every one knows that a ketone can yield two C-C bonds. This circumstance evolves into the realization that the tt and the a bonds of C=X both serve their individual purpose as potential precursors of C-C bonding. This allows the inclusion of imines, thioketones, and diazocompounds as functions capable of forming a maximum of two (FN = 2) C-C bonds. Similarly, esters, imino- and thioesters, and acyl halides display central carbons with FN = 3, while carbonates, carbamates, ureas, and carbon dioxide are all FN = 4 groupings. 

Recent progress in the chemistry of structurally well-defined lanthanide ketyl and ketone dianion complexes is reviewed, with particular emphasis on the ligand effects on the reactivity of these complexes. It has been demonstrated that the stability and reactivity of the ketyl radical and ketone dianion species strongly depend on the steric and electronic properties of the ancillary ligands, the structure of their parent ketones, as well as the nature of the metals to which they are bound. Fine-tuning these factors can control the reactivity of these species. Generation and reactions of dianionic thioketone and imine species are also briefly described. 

Similar to diaryl ketones, aromatic thioketones and imines can also be reduced to the corresponding dianionic species. Fujiwara and coworkers have reported that the ytterbium diaryl thioketone dianion species, generated by reaction of Yb metal with the thioketones in THF/HMPA at low temperature, show good nucle-ophilicity towards organic substrates such as acetone and alkyl halides (Scheme 22) [31]. The thioketone dianion species seemed to be less stable than those of ketones. At room or higher temperatures, C-S bond cleavage reaction took place. 

Reaction of N-(diphenylmethylidene)aniline with 1 equivalent of Yb metal in THF/HMPA gives the corresponding dianionic complex Yb(h2-Ph2CNPh)(HM-PA)3 (26) whose structure has been crystallographically determined (Scheme 23) [32]. The imine dianion complex 26 is more basic and less nucleophilic than ketone- and thioketone-dianion species. It reacts with C02 to give after hydrolysis the corresponding Yb(III) amino acid derivative [33],but with acetone to release... 

Alkenes lead to 1,4-dihydropyridazines (347) or the spiro derivatives (348). Cyclic alkenes, such as cyclopropenes give rise to diazanorcaradienes (349) or higher homologues, and reaction with alkynes yields pyridazines (350). Hetero-27r-systems such as nitriles, imines, thioketones, and N-sulflnylamines open the way to heterocyclic six-membered systems (351), (353), (357), and (356). (4-1-1) Addition reactions of isocyanides and carbenes make isopyrazoles (354) and (355) available. Reduction processes lead to 1,4- or 1,6-dihydrotetrazines (340) or (352). The reactions of 1,4-dihydrotetrazines (340) were briefly collected in Scheme 57. 

The 1,3-dipolar cycloaddition reaction of azomethine ylides with thioketones has been used to prepare 1,3-thiazoIidines. The metallated azomethine ylides 67 were generated in situ by treating a-amino acid ester imines 66 with lithium bromide and DBU. The ylides were then treated with highly reactive thioketones such as thiobenzophenone or fluorene-9-thione, to afford 1,3-thiazolidine derivatives 68 (main isomer) and 69 (minor isomer) in good yield and in diastereoisomeric ratios of between 2 1 and 4 1 <01H(55)691>. 

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