Imines sulfonylimines

Bode and co-workers have used NHCs to form y-butyrolactams 34 from enals 27 and saccharin-derived cyclic sulfonylimines 32. A range of [3-alkyl and [3-aryl substituted enals, and a variety of substituted imines, are tolerated in this reaction,... 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

A mechanistic rationale for the observed cw-selectivity has been proposed based on preorganisation of the Breslow-type intermediate and imine through hydrogen bonding 253, with an aza-benzoin oxy-Cope process proposed. Reaction via a boat transition state delivers the observed cw-stereochemistry of the product (Scheme 12.57). Related work by Nair and co-workers (using enones 42 in place of a,P-unsaturated sulfonylimines 251, see Section 12.2.2) generates P-lactones 43 with fran -ring substituents, while the P-lactam products 252 possess a cw-stereo-chemical relationship. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The preparation of imines, enamines, nitroalkenes and N-sulfonylimines proceeds via the azeotropic removal of water from the intermediate in reactions that are normally catalyzed by p-toluenesulfonic acid, titanium(IV) chloride, or montmorillonite K 10 clay. A Dean-Stark apparatus is traditionally used which requires a large excess of aromatic hydrocarbons such as benzene or toluene for azeotropic water elimination. 

An improved synthesis of a COX-2 inhibitor based on ring system 72 involves the cyclization of an imine intermediate formed between a 1-aminopyridazine salt and a benzyl ketone <2007TL911>. A tetrahydro derivative of ring system 73 has been prepared by dipolar cycloaddition of an iV-sulfonylimine to a diazafulvenium methide <2007JOC4406>. 

Aside from aldehydes, imines can be considered to be suitable substrates for the addition of reagents with umpoled carbonyl reactivity because useful building blocks and important compounds like a-amino acid and aldehydes will result from this conversion (Scheme 21). The S -configurated carbenoid 41 has been found to add to mesitylene-sulfonylimines 154, available from the corresponding aldehydes with predominant attack... 

The submitters employed a toluene solution of crude imine prepared in part B and obtained somewhat higher yields (90-95%). However, the checkers obtained yields in this range on one half the scale using isolated sulfonylimine. 

Quite recently, there has been significant expansion and development in the alkylation of imines with organozinc reagents using chiral Lewis acid catalysts. In 2000, Tomioka and co-workers reported a copper(II)-chiral amidophos-phine 4-catalyzed asymmetric process for the addition of diethylzinc to N-sul-fonylimines (Scheme 2) [8]. Excellent enantioselectivities (90-94%) and yields (83-99%) were obtained in reactions of N-sulfonylimines derived from arylal-dehydes. 

Shi and Xu reported that the chiral amine catalyst 142 also performs quite efficiently in the related addition of N-tosyl aryl imines to methyl vinyl ketone (MVK), to methyl acrylate, and to acrylonitrile (Scheme 6.61) [155]. As shown in Scheme 6.61, enantiomeric excesses > 95% were achieved for several />-N-tosylamino enones 147 obtained by addition of aryl imines (146) to MVK, > 80% for addition to methyl acrylate, and 55% ee (max.) for addition to acrylonitrile (not shown in Scheme 6.61). Reaction times were typically 1-3 days. N-Sulfonylimines derived from aliphatic aldehydes gave rise to complex product mixtures. Under the reaction conditions shown in Scheme 6.61 addition of p-nitrobenzaldehyde to MVK proceeded with only 20% ee. 

The 2-aroylaziridines (303), on thermolysis, provide aroylazomethine ylides which undergo [3 + 2] cycloadditions with various dipolarophiles. Whereas imines are normally inert to dipole synthons, Lown and Landberg reported that the polarized A -sulfonyl-a-acylimines afford initially the 1-sulfonyl-4,5-diacylimidazolines (304) which undergo cyclodehydration (Paal-Knorr reaction) to the furo[3,4-fi ]imidazolines (305) (Scheme 57). A further variant with other substituted A-sulfonylimines (R1 = 4-ClC6H4S02) and sequential amination affords the l,5-dihydropyrrolo[3,4-. 

In the absence of dipolarophiles the intermediate loses sulfur to give the carbodiimide however, the intermediate may be trapped with a number of alkenes, heterocumulenes and other reagents such as ynamines, ketenes, isocyanates, isothiocyanates, carbodiimides, ketenimines, sulfonylimines, imines, nitriles, thiocarbonyl compounds, Wittig reagents and the already mentioned enamines (80AG277). Contemporary knowledge of the chemistry of these sulfonyliminothiatriazolines is mainly due to the meticulous work of L abbe and his coworkers (80AG277). 

Benzothiazol 2-Amino-6-(2,2-dimethyl-propanoylamino)- E8b, 925 (1,4-Benzochinon—4-acyl-imin—1-sulfonylimin + KSCN)... 

PPG 425 has been used in the preparation of a range of benzaldehydes that were subsequently used in the solvent free synthesis of calix[4]resorcinarenes. The aldehydes are isolated in near quantitative yields by distillation from the PPG, which can be recycled. PPG has also been used in the indium metal mediated allylation of imines and sulfonylimines. Ultrasound was used for two reasons to clean the metal surface and to increase the solubility of the imine in PPG. The solvent was recycled three times, but a desire to develop an easier drying and recycling method was indicated. 

Preparation of imines and enamines from carbonyl compounds and amines can be achieved with a dehydrating agent under acid/base catalysis [563]. Basically, primary amines afford imines unless isomerization to an enamine is favored as a result of conjugation, etc (see Eq. 252), and secondary amines afford iminium salts or enamines. These transformations can be conducted efficiently with a catalytic or stoichiometric amount of a titanium salt such as TiCU or Ti(0-/-Pr)4. Equation (247) illustrates an advantageous feature of this method in the imination of a hindered ketone. f-Butyl propyl ketone resisted the formation of the imine even by some methods reported useful for sterically hindered ketones [564,565]. The TiCU-based method works well, however, for this compound, giving the desired imine in high yield within a relatively short reaction period [566]. Imine derivatives such as iV-sulfonylimines could be... 

The carbon-nitrogen double bond of imine derivatives has been shown to act as a radical acceptor. For example, it was shown that A-sulfonylimines are... 

The sulfonylimine 72 reacts with cyclopentadicnc in benzene at 0°C to afford solely the exo-adduct 73 in 84% yield (equation 48). The unstable imine 75, formed from the phosphorus compound 74 and ethyl glyoxylate by an aza-Witig reaction, adds to dienes in situ (equation 49)". ... 

The presence of a chiral sulfoxide group in the P-position allows the highly selective reduction of imines by Li 5-BU3BH or LiBEt3H [482, 1120] (Figure 6.20). Reduction of P-sulfonylimines with DIBAH/ZnCl2 at -78°C is also very efficient, and produces nonracemic amines after Raney nickel desulfurization [1121, 1122] (Figure 6.20). A chelated complex that is similar to the one involved in the reduction of p-ketosulfoxides ( 6.1.2.2) is proposed as a reaction intermediate. 

Carboxyl-substituted N-sulfonylimines have also been used in [4 + 2] cycloadditions, and some examples are shown in Scheme 2-11. - Imine 14 adds regioselectively to isoprene to give only one adduct, but diene 15 surprisingly afforder a 3 1 mixture of adducts. The major exo adduct produced from siloxydiene 16 was recently used in total synthesis of the piperidine alkaloids isoprosopinine B and deoxyprosopinine. The highly oxygenated diene 17 was found to react with both acyclic N-sulfonylimine 18 and cyclic imine 19 to afford cycloadducts. 

The frequency change is evident from the data for s-triazoles in Table II. The wavenumbers of the A-imine functional groups, except for the A-sulfonylimines, are shifted 100 cm-1 to lower values. The mean... 

Dialkylaluminum chloride. 20,126-127 Addition to imines. The adducts fror the addition to M-sulfonylimines, which is ... 

Reactions of imines. Silyl alkynyl ethers and aldimines undergo catalyzed condensation, the strained heterocycles that ensue open to afford conjugated amides. YbfOTfjj is also a useful catalyst for the reaction of organocuprates with N-sulfonylimines. ... 

The preparation of imines, enamines, nitroalkenes and N-sulfonylimines proceeds via azeotropic removal of water from the intermediate in reactions that are nor-... 

The Bode group disclosed NHC-catalyzed highly enantioselective annulations of a,P,P -trisubstituted enals with cyclic sulfonylimines. Mechanistically, it is proposed that the combination of enal and free NHC leads to the formation of the Breslow intermediate, which is oxidized to form the key a,p-unsaturated acyl azolium. Tautomerization between the imine and the enamine occurs readily in the presence of base, and the enamine is intercepted by the key a,p-unsaturated acyl azolium to form a hemiaminal which further engages in a Stork-Hickmott-Stille-type annulation via a tight-ion-pair/aza-Claisen type transition state. Lactam formation follows the protonation of enolate and brings about catalyst turnover to complete the catalytic cycle (Scheme 7.113). 

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