2- Amino-2- acetaldehyde

C synthons, synthetic equivalents of which being the amino-acetaldehyde-derived metallated aminonitrile D bearing the chiral auxiliary (S,S)-53 and an a,P-unsaturated ester E, respectively. This should make it possible to open up a pathway to an enantioselective conjugate addition of an a-aminoacyl carbanion equivalent D to enoates in order to access the target 3-substituted 5-ainino-4-oxo esters. 

A closely related variant of this novel strategy has also been applied to the efficacious total syntheses of ( )-haemanthidine (382) and ( )-pretazettine (395) (209). In the event (Scheme 47), sequential reaction of the zinc derivative of the metalloenamine 509 with the protected amino acetaldehyde 516, pivaloyl chloride, and then 3 N HC1 provided an intermediate 8-keto aldehyde, which underwent cycloaldolization and dehydration on treatment with pyrrolidine in 33% aqueous AcOH-MeOH to furnish 517 as a mixture (1.5 1) of diastereo-mers. The a -bromination of 517 with PhNMe3Br3 in EtOAc followed by dehydrobromination with DBU in refluxing benzene then provided the racemic cyclohexadienone 518. Palladium(0)-catalyzed removal of the A-allyloxycar-... 

Some pentaamine hgands are shown in (17), (19), and (207-215). Commercially available technical tetraethylene-pentamine is a mixture of linear tetren (207) and branched chain trenen (208), so five-coordinate [Cu(trenen)] + and octahedral [CoCl(tetren)] + can be obtained in reasonable yields from the same polyamine mixture.Alternatively, these ligands can be synthesized in situ from Co complexes of tren (191) ortrien (178), and coordinated amino-acetaldehyde. ... 

Amino acetaldehyde is a relatively awkward reagent in organic chemistry mainly because it condenses with itself rather readily. The problem can be overcome somewhat by coordinating the amine to a metal ion which renders it less accessible to the aldehyde group. 

The amino acetaldehyde protected as the dimethyl acetal reacts readily with a-[Co trien Cl2]+ ion to give an aminochloro complex which on treatment with acid yields the coordinated aldehyde shown. 

The a,(3-unsaturated ester (8), aldehyde (9), and nitro (10) compounds participate as electrophiles in a number of useful conjugate addition reactions. Copper-catalyzed addition of Grignard reagents provides access to aryl butanoic acid derivatives substituted with an oxetane (equation 1 in scheme 13.7). The ester, aldehyde, and nitro electrophiles also undergo mild Rh-catalyzed additions of aryl and vinyl boronic acids (equation 2 through equation 4 in scheme 13.7). Interestingly, the unsaturated aldehyde participates readily in an amine conjugate addition to afford oxetane substituted 3-amino-acetaldehyde derivatives. 

Illustrated below is the mechanism of the reaction between benzaldehyde and dimethyl O -amino acetaldehyde. 

The third important isoquinoline synthesis Is the Pomeranz-Fritsch reaction. Starting from benzaldehydes and an acetal of amino-acetaldehyde, one can obtain isoquinolines, often in moderate yield, by warming and treatment with sulfuric acid. 

Phthalimidoacetaldehyde diethyl acetal boiled 20 hrs. with 25%-KOH amino-acetaldehyde diethyl acetal. Y 85%.—At room temp., the corresponding phthal-amic acid is obtained in 80% yield (cf. Synth. Meth. 13, 50). F. Fischer and H. Riese, J. pr. 12, 177 (1961). 

In early 1983, the Korean company Shin Poong pursued a low-cost strategy to produce PZQ-(76) in bulk and to circumvent extensive patent protection, and thus became by 1993 the largest global producer of PZQ-(76). Their strategy involves treatment of chloroacetyl chloride (74) with phenylethylamine (77) to give (78), which then undergoes an amino alkylation reaction with amino acetaldehyde... 

The latest and most convergent addition to the manifold PZQ-(76) syntheses was described by Cao and Domling (Scheme 15.26) [38]. This efficient synthesis employs, as a key step, an Ugi four-component reaction (U CR) between the readily available cheap starting materials phenylethyl isocyanide (84), formaldehyde (86), amino acetaldehyde dimethyl acetal (85), and cyclohexane carboxylic acid (87). The Ugi reaction gives the advanced intermediate 88 in quantitative yield under mild conditions. Compound 88 can be converted into PZQ-(76) by a Pictet-Spengler reaction under strongly acidic conditions. Overall, this short two-step process affords PZQ-(76) from inexpensive and readily available starting materials in 70% yield. 

Isolation of the carbinolamine intermediate (66) is possible in the reaction of 2-amino-5-nitrothia2ole with acetaldehyde (Scheme 46) (216). 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

Ethanol, acetaldehyde, acetic acid, acetone, glycerol, n - butanol, n - butyric acid, amyl alcohols, oxalic acid, lactic acid, citric acid, amino acids, antibiotics, vitamins... 

Numerous variations of this reaction have been studied, principally those involving a prior inclusion of the nuclear sulfur atom in a thioacylamino compound. Thus, thiobenz-amido acetaldehyde diethyl acetal (8) underwent ring closure to 2-phenylthiazole (9) on gentle heating (57JCS1556). Similarly, iV-thioacyl a-amino acids also undergo ready ring closure to thiazoles. 

Tryptophan (15) and its substituted derivatives also react with aldehydes to give l,2,3,4-tetrahydro-jS-carboline-3-carboxylic acids (17), Acetaldehyde and benzaldehyde yield the expected products with the amino acid and its A -methyl derivative (abrine). ... 

The Maunich reaction of a ketone, an amine, and an aldehyde is one of the few three-component reactions in organic chemistry. Cyclohexanone, for example, reads with dimethylamine and acetaldehyde to yield an amino ketone. The reaction takes place in two steps, both of which are typical carbonyl-group reactions. 

The synthesis of the E-ring intermediate 20 commences with the methyl ester of enantiomerically pure L-serine hydrochloride (22) (see Scheme 9). The primary amino group of 22 can be alkylated in a straightforward manner by treatment with acetaldehyde, followed by reduction of the intermediate imine with sodium borohydride (see 22 —> 51). The primary hydroxyl and secondary amino groups in 51 are affixed to adjacent carbon atoms. By virtue of this close spatial relationship, it seemed reasonable to expect that the simultaneous protection of these two functions in the form of an oxazolidi-none ring could be achieved. Indeed, treatment of 51 with l,l -car-bonyldiimidazole in refluxing acetonitrile, followed by partial reduction of the methoxycarbonyl function with one equivalent of Dibal-H provides oxazolidinone aldehyde 52. 

Auxiliary-controlled Streeker syntheses have so far only been carried out with amines serving as the chiral components. In the first asymmetric Streeker synthesis a solution of sodium cyanide, ( — )-(S)-a-methylbeuzylamine and its hydrochloride in water was mixed with a methanolie solution of acetaldehyde and stirred for five days. Hydrolysis of the resulting amino nitrile and subsequent hydrogenolysis furnished L-alanine with 90% optical purity 38-39-85. 

A very elegant approach has been developed by Kanerva et al. DKR of N-hetrocyclic a-amino esters is achieved using CAL-A [54]. Racemization occurs when acetaldehyde is released in situ from the acyl donor. In this case aldehyde-catalyzed racemization of the product cannot occur (Figure 4.28). This is one of the few examples reported for DKR of secondary amines (For a recent example see the above text and Ref. [38]). 

Figure 4.28 DKR of -amino esters catalyzed by CAL-A and acetaldehyde released in situ.

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