Imines aldol-type condensation

Phosphine imines -, aldol-type condensation, stereo-specific with - 44, 558... 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

Ishii has shown that diversely substituted pyrroles 152 can be prepared by a one-pot operation involving formation of intermediate a,/ -un saturated imines 153 via a SmCl3-catalyzed self-aldol-type condensation. The targeted heterocydes are formed upon addition of a nitroalkane and subsequent cyclization according to the mechanism depicted in Scheme 8.64 [140]. Interestingly, a,/i-unsaturated ketones also participate in this process. 

It should also be noted that some pathways to be discussed below depend on highly unusual chemical reactions. To give just one example, the formation of the pyridine ring system of vitamin Be depends on a protein that catalyzes a complex series of reactions, including carbohydrate isomerization, imine formation, ammonia addition, aldol-type condensation, cycliza-tion, and aromatization (9). 

Of the various imines known to condense with active methylene compounds, a-arylimines have been the most widely used, especially in earlier work, because of their stability, ease of preparation and the absence of enolizable protons. Aliphatic imines containing enolizable protons have broader synthetic applications but their use is more restricted because they are prone to deprotonation and self aldol type condensations. As will be discussed, new methods utilizing Lewis acids and the less basic boron enolates have been devised to overcome the problem of deprotonation. Other innovations that have extended the scope of imine condensations include in situ methods for the preparation of elusive formaldehyde imines (CH2=NR2> and the utilization of A/-heterosubstituted imines (N = Si, O and S) for the synthesis of primary Mannich bases and A(-unsubstituted 3-lactams, available via hydrolysis or reduction of the N—X bond. 

The biosynthesis of porphyrin involves the formation of porphobilinogen from two molecules of S-aminolevulinic acid. The precise mechanism for this biosynthesis is as yet unknown. A possible mechanism starts with the formation of an imine between the enzyme that catalyzes the reaction and one of the molecules of S-aminolevulinic acid. An aldol-type condensation occurs between the imine and a free molecule of d-aminolevulinic acid. Nucleophilic attack by the amino group on the imine closes the ring. The enzyme is then eliminated, and removal of a proton creates the aromatic ring. 

A stereoselective synthesis of 6-amino acid derivatives by an aldol-type condensation of tin(II) carboxylic thioester enolates with imines has been reported (Scheme 90) the method was used to synthesize an intermediate of the carbapenem antibiotic... 

This route depends on the samarium-catalysed aldol-type condensation of nitroalkanes with imines generated from amines and aldehydes, all three components being... 

The reaction is proposed to proceed via a two-step sequence (i) catalytic car-bonylation of the olefinic C-H bond of a,/i-unsaturated imines after insertion of ethylene and (ii) intramolecular nucleophilic attack of the imine nitrogen on the ketonic carbon followed by a 1,2-ethyl migration (Scheme 7.13). The initial formation of ethyl ketone was confirmed by the reaction of a cyclic unsaturated imine, which produced a -aminocyclopentene derivative via an aldol-type condensation of the initially formed ketone (Eq. (7.54)). 

Murai et al. in 1997 developed the carbonylation of aromatic imines for the preparation of indenones in the presence of Ru3(CO)j2 [10]. This process runs under 7 bar of ethylene and 5 atm of CO at 160 °C (Table 15.5). Control experiments demonstrated that one-pot two-step manner is involved first, the carbonylation of aromatic imines with CO and ethylene giving the keto imine and then the intramolecular aldol-type condensation of ketoimine would readily undergo to generate 1 in situ. Treatment of the crude reaction mixture with silica gel resulted in the elimination of ieri-butylamine from 1 and deliverance of the final product. 

Aldol-type reactions. In the presence of I r. h, these ketals condense with aldehydes to form p-hydroxy carboxylic acids (equation 1) ir with imines to form P-lactams (equation 11). 

On the basis of these results, we have developed the first method for the enantiose-lective synthesis of chiral /3-amino acid esters from achiral imines and ketene silyl acetals using BLA 28. The enantioselectivity of the aldol-type reaction is dramatically increased by using sterically bulky A-substituents. Condensation of the imine derived from benzhydrylamine occurs with high enantioselectivity (90 % ee) (Eq. 80). Furthermore, the best result (96 % ee) is achieved by use of a 1 1 (v/v) mixture of toluene and dichloromethane as solvents. Thus, excellent enantioselectivity (95 % ee or better) has been achieved in reactions of aromatic aldehyde-derived imines... 

Aldol-type reactions. The highest anti selectivity is observed with BINAP complex of Pd(OTf)j in the aldol reaction of tin enolate of cyclohexanone. The condensation of silyl enol ethers with imines provides y-keto a-amino esters. ... 

The synthesis of carboxylate-substituted imidazoline derivatives has previously been accomplished by the condensation of presynthesized 1,2-diamines with amides, or through the transition metal catalyzed aldol-type reaction between isocyanates and imines (4,5). We have recently communicated an alternative palladium catalyzed route to synthesize a new class of imidazoline carboxylates, utilizing acid chloride, imines and carbon monoxide as starting materials (see Table 1)... 

In Section 9.4.A, it was noted that there were problems with aldol-type reactions, especially with the directed aldol condensation. In particular, aldehydes with an a-hydrogen have great difficulty adding to ketones due to their propensity for self-condensation. The ability to use kinetic control conditions in enolate reactions of ketones and aldehydes often solves this problem. There are also several alternative approaches that involve the use of carbanions derived from imines and hydrazones and these can be very useful. l... 

The Knoevenagel reaction is a base-catalyzed aldol-type reaction that can occur through two possible mechanisms, depending on the type of base used. When Emil Knoevenagel made his initial discovery of this reaction, it was already known that benzaldehyde could condense with two equivalents of piperidine to provide the benzylidine bispiperidine aminal 1 Therefore, he proposed the intermediacy of an aminal (or imine) in the condensation. 

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

Antibacterial activity has also been observed with a variety of sulphameth-oxypyridazine derivatives like the imine obtained upon reaction of (95, R1 = MeO R2 = H) with 5-nitrofurfural [312], 2-aryl-3-nitrofurylacrylamides (105) [313], quinazoline-2,4-diones (106) [314], thiazolin-4-ones of type (107) [315] and with aldol condensation products of the latter [316], Sulpnonylpyridazmones (108, R1, R3 = alkyl, Ph R2 = substituted NH2, HO, RO) [273,274], trichloromethylchloropyridazines (109) [317] and 3-mer-captopyridazine 2-oxide derivatives [318, 319] have been claimed as antibacterial agents. 

Metal template syntheses of complexes incorporating the p-amino imine fragment have been introduced by Curtis as a result of his discovery that tris(l,2-diaminoethane)nickel(II) perchlorate reacted slowly with acetone to yield the macrocyclic complexes (40) and (41) (equation 8).81-83 In this macrocyclic structure the bridging group is diacetone amine imine, arising from the aldol condensation of two acetone molecules. This reaction is widely general, in the same way that the aldol reaction is, and can be applied to many types of amine complexes. The subject has been reviewed in detail with respect to macrocyclic complexes by Curtis.84... 

Bemardi, F., Bongini, A., Cainelli, G., Robb, M. A., Valli, G. S. Theoretical study of the aldol condensation with imine-type electrophiles. J. Org. Chem. 1993, 58, 750-755. 

Largely stimulated by the synthesis of 3-lactam antibiotics, there have been widespread investigations into the stereochemical aspects of imine condensations, mainly involving reactions of enolates of carboxylic acid derivatives or silyl ketene acetals. In analogy to the aldol condensation, stereoselectivity of imine condensations will be discussed in terms of two types in this chapter (i) simple dia-stereoselectivity or syn-anti selectivity, when the two reactants are each prochiral (equation 12) and (ii) diastereofacial selectivity, when a new chiral center is formed in the presence of a pre-existing chiral center in one of the reactants (e.g. equation 13). The term asymmetric induction may be used synonymously with diastereofacial selectivity when one of the chiral reactants is optically active. For a more explicit explanation of these terms, see Heathcock s review on the aldol condensation. ... 

Condensation reactions of simple carboxylic acids with imines are of intense interest because of their applications to 3-lactam synthesis. Activation of the carboxylic acid derivative is accomplished by preforming the enolate in situ or by using a silyl ketene acetal derivative with Lewis acid catalysis. The first example of an enolate-imine condensation of this type can be attributed to Gillman and Speeter, who in 1943 reported the synthesis of 3-lactams from Reformatsky reagents and Schiff bases. Subsequently, other workers have investigated the mechanism and syn-anti selectivity of this reaction. A review of these studies by Evans et al. covering work through 1980 has appeared in their review, Stereoselective Aldol Condensations . ... 

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