Diastereomeric imines

In einer Eintopf-Reaktion bilden racemische Aminosauren mit (S)-2-[(N -Benzyl-prolyl)-amino]-benzaldehyd bzw. -acetophenon und Kupfer(II)-Ionen diastereomere Imin-Kom-plexe im Verhaltnis 1 1 (vgl. S. 500) ... 

Resolution of Asymmetric Aldehydes. The resolution of the aldehyde-containing natural product ( )-gossypol has been accomplished by chromatographic separation of (7), the diastereomeric condensation product between (1) and gossypol hexaacetate. Other chiral primary amines commonly used for the resolution of aldehydes and ketones by physical separation of diastereomeric imines include 2-amino-1-butanol, a-methylbenzylamine, and Betti s base (8). ... 

Resolution of 2,2 -diformylbiphenyls. The chiral sulfinamide forms separable diastereomeric imines with the biphenyldialdehyde, wherefrom optically active aldehydes ate obtained. ... 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Addition of Grignard and organolithium reagents to imines 2. derived from enantiomerically pure (S)-valinol (1), provides a-substituted phenethylamines 3 in moderate to good yield and excellent diastereoselectivity (in each case only one diastereomer can be detected by NMR)15. By appropriate selection of imine and organometallic reagent both diastereomeric amines are accessible (see also refs 16 and 17). 

Furthermore, intramolecular cyclization of acyclic chiral imines, in which the imine and the enone groups are separated by alkyl chains, yield optically active cyclohexane and cyclopentane derivatives. /ra .v-l,2-Disubstitutcd carbocyclic compounds are exclusively or predominantly formed with diastereomeric ratios in the range 80 20 100 0, strongly dependent on the conditions used to induce cyclization, i.e. heat, pressure or Lewis acid (MgBr2) catalysis227. 

More recently, the addition of cyanide ion, generated from TMS cyanide and cesium fluoride, to a-aziridino N-siflfinyl imines, being chiral either at the a position or at sulfur, has been examined [87] (Scheme 28). The configuration of the newly formed stereocenter was determined only by the chiral (S)-sulfinyl group. In fact, the R configuration (diastereomeric excess, de, 98%) was obtained from either the Q -(ii)-imine 186 or the a-(S)-imine 188, giving 187 and 189, respectively. Acyclic 2,3-diaminonitriles can be obtained... 

In this context, also mentionable are several publications by the groups of Dlaz-de-Villegas [242], Guarna [243], Kunz [244] and Waldmann [245], which describe the formation of six-membered azaheterocycles via treatment of an imine with an appropriate substituted diene. For instance, as described by Waldmann and coworkers, reaction of the enantiopure amino acid-derived imines 2-452 with Danishefsky s diene 2-453 in the presence of equimolar amounts of a Lewis acid provided diastereomeric enaminones 2-456 and 2-457 (Scheme 2.105) [245a]. 

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

A Lewis acid-induced aza-Diels-Alder reaction between the /3-lactam-imine 295 and 3,4-di hydro-2//-pyran gives the two diastereomeric pyranoquinolines 296 and 297. Under basic conditions, these products rearrange to the amino-substituted pyranoindolizinones, 298 and 299, respectively, with retention of stereochemistry (Scheme 74) <2003CEJ3415>. 

Allenylsilanes 159 (Eq. 13.53) and 161 (Eq. 13.54) differ in the axial stereochemistry of the allene function. In each case, formation of the benzyl imine, followed either by treatment with tin(IV) chloride in benzene at room temperature or heating in toluene, leads to diastereomeric products 160 and 162 [63], Significantly, there is no crossover, pointing to a concerted (or fast, stepwise) process. Since the absolute stereochemistry of the allenylsilanes is easily controlled, the methodology is ideal for applications in total synthesis. Weinreb and co-workers have used the reaction for his synthesis of the marine natural product (-)-papuamine. 

Hetero Pauson-Khand reactions with an aldehyde or ketone component have been shown to afford synthetically versatile y-butyrolactones. Buchwald [50] and Crowe [51] independently showed that aliphatic enones and enals react with CO under Cp2Ti(PMe3)2 mediation (Scheme 11). CO insertion and thermal (or oxidative) decomposition gave diastereomerically pure bicyclic y-butyrolactones and stable Cp2Ti(CO)2. Imines did not react under the reaction conditions. 

Protonated imines are effective dienophiles. Thus in the reaction of methyl glyoxylate with the hydrochloride 127 of alanine methyl ester in the presence of cyclopentadiene, a mixture of hydrochlorides of the exo- and ewrfo-adducts 128-131 was formed (equation 69). The diastereomeric ratio of the exo-compounds was 83 1761. 

Reformatsky reaction has covered aspects of this topic (20b). If analogous pericyclic transition states are involved in these condensations, the added stereochemical control element imposed on the condensation by the imine geometry should provide a more well-defined set of transition states than for the analogous aldehyde condensations. The four diastereomeric chair and boat transition states for ( )- and (Z)-enolates with ( )-imines are illustrated in Scheme 15. 

To form the stereocenter at C-3 a direct reduction-alkynylation sequence was applied, that provided the diastereomeric homopropargylic alcohols 83 in a ratio of syn anti=76l2A, The major isomer syn-S3 was isolated in 55% yield. The key step of the synthesis was an intramolecular imidotitanium-al-kyne [2+2] cycloaddition/acyl cyanide condensation. With this sequence the pyrrolidine ring was formed and all the carbon atoms of the alkyl side chain were established in acrylonitrile 84. The reduction of the imine double bond proceeded stereoselectively and the nitrile group was removed reductively en route to the target compound. 

Figure 1.31. Reaction mechanism and diastereomeric transition states of titanocene-catalyzed hydrogenation of imines.

The methodology was extended to an asymmetric introduction of snbstitnents to a naphthalene ring. When chiral naphthyloxazolines 13 were used as substrates, di- or trisubstituted dihydronaphthalenes 15 were obtained in high diastereomeric ratio (dr) after the treatment of intermediate azaenolate 14 with an electrophile (equation 7) °. Analogous reactions with a chiral naphthaldehyde imine were also reported . 

The observed diastereoselectivity in the asymmetric Strecker step via the crystallization-induced asymmetric transformation can be explained as shown in Figure 2. Apparently, the re face addition of CN to the intermediate imine 4 is preferred at room temperature in methanol and results in a dr 65/35. At elevated temperatures in water, the diastereomeric outcome and yield of the process are controlled by the reversible reaction of the amino nitriles 3 to the intermediate imine and by the difference in solubilities of both diastereomers under the applied conditions. . .. 

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