Heterocycles from aldehydes

The second approach for the synthesis of 2-amino-3-hydroxycarboxylic acids starts with a chiral isothiocyanate which is added, via the tin enolate, to aldehydes. The initially formed adducts are immediately derivatized to the heterocycles, from which. yj 7-2-amino-3-hy-droxycarboxylic acids result after a three-step procedure. The diastereomeric ratios of the intermediate bis-heterocyclic products range from 93 7 to 99 1 (desired isomer/sum of all others)104. 

Five- and Six-Membered Ring Heterocycles with One, Two, or Three Sulfur Atoms. A summary of the various sulfur heterocycles formed from aldehydes in the presence of hydrogen sulfide and the corresponding analytical data are presented in Table I. Examples of aldehydes used in this reaction include propionaldehyde, butyraldehyde and caproaldehyde. 

The classical Biginelli synthesis of heterocycles from /3-diketones, urea, and aldehydes has been extended by the replacement of the dione with a cycloalkanone.343 The... 

An alternative method for the substitution of a hydrogen atom in -electron deficient heterocycles is using the nucleophilic character of radicals in homolytic aromatic displacement reactions <74AHC(16)123>. Acylation with acyl radicals derived from aldehydes is an especially important approach since Friedel-Crafts-type reactions are not applicable to pteridines. 

The assumption that the azomethine 34 is formed by an intermolecular hydride transfer from aldehyde 30 to the nitrilium salt 31 is not confirmed because the different Schiff bases 34 obtained carry the group R which are originated from the aldehyde 30. In this way, the process described in equation 14 can be reversed and applied as an enamide synthesis by acylation of imines2,3. However, the 7V-ethylbenzonitrilium salt 35 reacts with benzaldehyde to give the more stable Af-benzoyl-7V-ethyliminium ions 3647,49 which add to trimethylethylene to form 5,6-dihydro-4i/-l,3-oxazinium salt 37. On the other hand, the reaction of ions 36 with phenylacetylene leads to another type of 1,3-oxazinium heterocycle, namely to 4i/-l,3-oxazinium hexachloroantimonate 38 (equation 15). 

Besides the Michael addition of heteroatomic nucleophiles initiating cyclocondensations, acceptor substituted unsaturated systems can also be reacted with carbon nucleophiles stemming from aldehydes in the sense of an umpolung, generally referred to as the Stetter reaction [244-246]. This process is organocatalytic and furnishes in turn 1,4-dicarbonyl compounds, intermediates that are well suited for Paal-Knorr cyclocondensations giving rise to furans or pyrroles. Among numerous heterocycles furans and pyrroles have always been the most prominent ones since they constitute important classes of natural products [247-249], of synthetic... 

A variety of aldehydes—aliphatic, aromatic, and heterocyclic—have been condensed with hydantoin. Sodium acetate in a mixture of acetic acid and acetic anhydride as well as pyridine containing traces of piperidine serves as condensing agent. Reduction of the double bond is accomplished with phosphorus and hydriodic acid, ammonium sulfide, or stannous chloride, In a more recent modification, the hydantoins are synthesized from aldehyde or ketone cyanohydrins and ammonium... 

Many heterocyclic compounds are made from aldehydes and ketones by reduction procedures which have been applied in the synthesis of hydrocarbons (method 3). Typical examples are considered here. 

Three-component reactions of aldehydes, amines, and allyltributyltin also proceeded smoothly in micellar systems with Sc(OTf)3 as Lewis acid catalyst, to afford the corresponding homoallylic amines in high yields (Eq. 19) [68]. Not only aromatic aldehydes but also aliphatic, unsaturated, and heterocyclic aldehydes worked well. The procedure is very simple—merely mixing an aldehyde, an amine, and allyltributyltin in the presence of Sc(OTf)3 and SDS in water no homoallylic alcohol (an adduct between an aldehyde and allyltributyltin) was produced. It was suggested that imine formation from aldehydes and amines was very fast under these conditions, and that the selective activation of imines rather than aldehydes was achieved. 

A Grignard type of addition of alkynes to in situ generated imines from aldehyde and amines, catalyzed by CuBr, provides an efficient solvent-free approach for the synthesis of substituted N-heterocycles such as propargyla-mines in excellent yields (Scheme 8.17). ... 

Original 1,2,4,5-tetrazines disubstituted by heterocyclic rings have been prepared and their electrochemical and spectroscopic properties studied <04NJC387>. A bowl-shaped neutral radical with a core annulene system bearing a verdazyl radical 47 has been synthesized in two steps from aldehyde 44 and carbazide derivative 45, as a stable solid in air <04OL1397>. 

Heterocycles. Many different heterocycles are synthesized via a carbonylation process hydantoins from aldehydes and urea, flavones from ethynylarenes and o-iodophenol acetates, and a-substituted a,p-unsaturated lactones from iodoalkenols. ... 

NCS can also be employed as an oxidant to promote the formation of heterocycles from diamine derivatives and aldehyde. The aldehyde moiety is oxidized by NCS, and finally imidazoline is obtained as the product. This method has been used in the late-stage of total synthesis (eq 51). ... 

An intermolecular version of the Sakurai reaction has been developed. It proceeds at temperatures as low as —78°C, using substoichiometric amounts of the Lewis acid, to form five-or six-membered oxygenated heterocycles from cyclic allylsilox-anes and aldehydes through a chairlike transition state (eq 65). Acetals may also act as electrophiles in this kind of reaction. /3-Borylallylsilanes also undergo nucleophilic allylation to lead to the preparation of functionalized alkenylboranes, which may participate in further transformations. ... 

---