Aldimines cyclic

Various phenyl-substituted ketimines and aldimines react with metallocenes 1 and 2, in a manner that depends on the substituents present [41]. In all cases, elimination of the al-kyne is observed. Complex 2b reacts with PhN=CMePh to give the r 2-complex 64, which is stabilized by an additional pyridine ligand [41a], In the reactions of 1 or 2a with the ketimine HN=CPh2, hydrogen transfer generates complexes 65. Two molecules of the aldimine PhN=CHPh are coupled by 2a to give the cyclic diamido complex 66 [41b]. 

The addition of an amine to the carbonyl group of an aldehyde yields—after removal of water—an aldimine (not shown see p. 178). Aldimines are intermediates in amino acid metabolism (see p. 178) and serve to bond aldehydes to amino groups in proteins (see p. 62, for example). The addition of an alcohol to the carbonyl group of an aldehyde yields a hemiacetal (R-O-C(H)OH-R). The cyclic forms of sugars are well-known examples of hemi-... 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

Akiyama applied Im in the inverse-demand aza-Diels-Alder reaction of various acyclic and cyclic vinyl ethers with N-aryl imines derived from o-hydroxyaniline to provide ophcally active tetrahydroquinoline derivatives (Scheme 5.16) [29]. Since aldimines derived from p-methoxyaniline gave no cycloaddition product, a nine-membered cyclic TS (akin to that proposed for the author s Mannich reachon) was invoked to rationalize the high levels of enantio-control. 

Addition of an allylic zinc reagent to cyclic aldimines has been reported129. Lithiated bisoxazoline 61 and allylzinc reagent form the reactive species, which adds to a cyclic aldimine enantioselectively with up to 97.5% (equation 29)129. 

Reaction of 9-[chloro(dimethylamino)methylene]tetrahydropyrido[l, 2-a]pyrimidin-4-ones 608 and aldimines or ketimines 609 in chloroform and acetonitrile gave a diastereomeric mixture of tricyclic compounds 611 and 612 at room temperature (82BEP892120, 82TL2891). The formation of compound 610 and the formation of a 1 1 mixture of the tricyclic products 611 and 612 could be detected by H NMR spectroscopy (82TL2891). After refluxing the reaction mixtures, only the thermodynamic product 611 could be isolated in pure form. 9-[Chloro(dimethylamino)methylene] derivatives 608 (R = CN, COOEt) also reacted with cyclic imines to yield the corresponding tetra- and pentacyclic quaternary salts, similar to 611 and 612 (87H2615). 

It appears probable that the aldimine II, initially formed by hydrogenation of the nitrile group, is itself in the stabilized, cyclic-hemiacetal form as a 1,2-diamino-l, 2-dideoxy derivative (III), the 1-amino group of which is subsequently hydrolyzed to yield the cyclic 2-amino-2-deoxy sugar (IV) directly.10 10a... 

Cyclic enones such as cyclopentenone or cyclohexanone were inert under the above-mentioned conditions. The reaction of aryl aldimines to cyclic enones can be mediated, however, with the more nucleophilic phosphine 119f [101], although the ee-value of the reactions is usually low (Table 5.17). 

Synthesis of homoallylic amines has been reported by a three-component coupling of aldimines, diiodomethane, and alkenylzirconocenes, in the presence of dimethylzinc (Scheme 28).296,296a The formation of homoallylic products is rationalized by the mechanism shown in Scheme 29. The //////-relationship of the final product is explained by a cyclic chair-like transition state. This type of homologation was used to form f, -dicyclop ropy I ruethylamines by a double C,C-cr-bond insertion into bicyclobutanes (Scheme 30).297 During the course of this cascade process, 10 C,C-bonds are formed, and the final product is isolated in one step with a high diastereoselectivity. 

Asymmetric addition of phosphorus compounds to C-N double bonds has been widely studied and mainly concerns the synthesis of chiral a-aminophosphonic acids (for reviews on the synthesis of aminophosphonic acids, see refs 36, 37 and 67). For this purpose, the following types of organic nitrogen compounds have been used aldimines and cyclic imines, nitrones, ureidoimino derivatives and imidothioloesters. A separate example is the addition of dialkyl phosphites to hydrazones, which was used for the synthesis of phosphonosugars. 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

Cyclic aldimines can also be used, and subsequent alkylation of the magnesioenamine intermediate achieved with good to excellent diastereoselectivity. Cis or trans products can be obtained, depending on the procedure chosen (eq 5). 

A few natural product syntheses feature the use of both acyclic and cyclic aldimines of either enantiomer of f-leucine f-butyl ester. Kinetic resolution of racemic aldehydes has also been achieved using L-f-leucine f-butyl ester. ... 

Although 1,2-dicarbonyl substrates (especially unsymmetrical benzils) are often difficult to make, there are a number of approaches which may be appropriate. Propane-1,3-dithiol reacts with aldehydes to give cyclic thioacetals (in 52-91% yields) which form stable dithiane anions when treated with butyllithium. Subsequent quenching with an acid chloride followed by mercury(ll) chloride treatment gives a 1,2-dicarbonyl species. Alternatively, substitution of an aldehyde for the acid chloride gives rise eventually to an a-hydroxycarbonyl derivative (Scheme 5.1.2) [16j. An alternative approach to a-ketoaldehydes (82-86% yields) reacts an a-ketonitrate ester with sodium acetate in DMSO [17]. Aryl a-diketones can be made from a-ketoanils, which are in turn made by cyanide ion-catalysed transformation of aromatic aldimines [18], and the range of unsymmetrical benzils has been increased by... 

Diethanolamine will react with acids, acid anhydrides, acid chlorides, and esters to form amide derivatives, and with propylene carbonate or other cyclic carbonates to give the corresponding carbonates. As a secondary amine, diethanolamine reacts with aldehydes and ketones to yield aldimines and ketimines. Diethanolamine also reacts with copper to form complex salts. Discoloration and precipitation will take place in the presence of salts of heavy metals. 

In summary, notable advances have been made in controlling stereoselectivity resulting ffom the addition of nonstabilized carbanions to chiral imine/imine derivatives. Unfortunately our level of mechanistic understanding in these additions is unsatisfactory. While additions involving chiral nitrones, hydrazones and some cyclic imines have been evaluated in reasonable detail, few systematic studies of other al-dimine/aldimine derivatives are available. 

Iminium salts bearing a labile trimethylsilyl group can be generated in situ and undergo nucleophilic addition (see Sections 1.12.4.2 and 1.12.7.3). Bis(trimethylsilyl)methoxymethylamine (75), for example, has been used as a formaldehyde equivalent for the preparation of primary amines. Cyclic imines, such as 3,4-dihydroquinolines, react with trimethylsilyl triflate (TMS-OTf) to provide reactive labile iminium salts (55), which condense with picoline anions. The addition of nonstabilized Grignard and organolithium reagents to acyclic aromatic ketimines and aldimines, however, is often not facilitated by the presence of TMS-OTf ... 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

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