Amino alcohols, preparation

Preparation of a Na-Protected a-Amino Aldehyde via Oxidation of the Corresponding 11-Amino Alcohol Preparation of a (1-Amino Alcohol by Reduction of the Mixed Anhydride of a Na-Protected a-Amino Acid 35 ... 

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

A different conceptual approach to amino-alcohol preparation Involved use of chiral N,0-heterocycles as templates for enantiospecific syntheses of these compounds. Alkylations of the carbanion derived from 2-cyano-6-oxazolopiperidine (36) had been successfully applied to the synthesis of a number of alkaloids. 

Phenylpropanolamine. - With catalyst prepared as previously described from 0.5g of palladium chloride and 3g of charcoal, it was possible to reduce two portions of 9.8g of isonitrosopropio-phenone (0.06 mol), dissolved in 150 cc. of absolute alcohol containing 7. Og of hydrogen chloride, to phenylpropanolamine in from 145 - 190 minutes with yields of the isolated chloride from 9.4g to 11. Og, or 84 to 98% of the theoretical. After recrystallization from absolute alcohol the salt melted at 191°. The free base was obtained by treating an aqueous solution of the hydrochloride with alkali on cooling, the liberated amino alcohol solidified and after recrystallization from water melted at 103°."... 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Many members of this series are known based on nitroparaffin condensations with aldehydes of longer chain length than formaldehyde. However, only the five primary amino alcohols discussed in the following are manufactured on a commercially significant scale. N-Substituted derivatives of these compounds also have been prepared, but only 2-dimethylamino-2-methy1-1-propanol has been available in commercial quantities (Table 1). 

Some substituted alkyl hydrogen sulfates are readily prepared. Eor example, 2-chloroethyl hydrogen sulfate [36168-93-1] is obtained by treating ethylene chlorohydrin with sulfuhc acid or amidosulfuhc acid. Heating hydroxy sulfates of amino alcohols produces the corresponding sulfuhc monoester... 

Amino Alcohols. Reaction of chloroformate is much more rapid at the amino group than at the hydroxyl group (4—8). Thus the hydroxy carbamates, which can be cyclized with base to yield 2-oxazoHdones, can be selectively prepared (29). Nonionic detergents may be prepared from poly[(ethylene glycol) bis(chloroformates)] and long-chain tertiary amino alcohols (30). 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Acrylic Esters. A procedure has been described for preparation of higher esters from methyl acrylate that illustrates the use of an acid catalyst together with the removal of one of the products by azeotropic distillation (112). Another procedure for the preparation of butyl acrylate, secondary alkyl acrylates, and hydroxyalkyl acrylates using -toluenesulfonic acid as a catalyst has been described (113). Alurninumisopropoxide catalyzes the reaction of amino alcohols with methyl acrylate and methyl methacrylate. A review of the synthesis of acryhc esters by transesterification is given in Reference 114 (see... 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

These hydrazides on treatment with nitrous acid are converted into azides, which with appropriate amino-alcohols, furnish ergometrine and its isomerides and analogues. The four pairs of stereoisomeric ergo-metrines and ergometrinines in the following list have been prepared in this way with l-( -(-)-)S-aminopropyl alcohol or its d-( —)-isomeride. 

Due to the abundance of epoxides, they are ideal precursors for the preparation of P-amino alcohols. In one case, ring-opening of 2-methyl-oxirane (18) with methylamine resulted in l-methylamino-propan-2-ol (19), which was transformed to 1,2-dimethyl-aziridine (20) in 30-35% yield using the Wenker protocol. Interestingly, l-amino-3-buten-2-ol sulfate ester (23) was prepared from l-amino-3-buten-2-ol (22, a product of ammonia ring-opening of vinyl epoxide 21) and chlorosulfonic acid. Treatment of sulfate ester 23 with NaOH then led to aziridine 24. ... 

In addition, an Organic Synthesis procedure of preparing aziridine from P-amino alcohol exists. ... 

One scheme for preparation of the diamine side chain consists in first reducing the carbonyl group of the haloketone, 73. Displacement of the halogen with diethylamine gives the amino alcohol (74). Treatment of that intermediate with thionyl bromide serves to replace the hydroxyl by bromine (75). The synthesis is completed by displacement of the bromine with ammonia. 

In an alternate approach to the preparation of compounds containing the additional ring, haloamide, 41 (obtained from the aminobenzophenone and bromoacetylbromide) is alkylated with etha-nolamine to afford 42. Treatment of the amino alcohol in acetic acid affords the carbonyl addition product, 43, at the same time... 

Ring-opening of diastereomerically pure vinylaziridine 131, prepared by azir-idination of butadiene with 3-acetoxyaminoquinazolinone 130 [52], yielded acetate 132 with inversion of configuration, together with amino alcohol 133 with retention (Scheme 2.34) [53]. The formation of 133 can be explained by assuming participation by the quinazolinone carbonyl oxygen, which produces an intramolecular reaction with the aziridine carbon with retention of configuration. 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

Reviews concerning the preparation and use of syn-P-amino alcohols Bergmeier,... 

Another chiral auxiliary used in diastereoselective addition reactions is the 1,3-oxazine derivative 4a which shows a close structural resemblance to the 1,3-oxathiane 16 (vide supra). However, in contrast to the oxathiane, 4a cannot be readily acylatcd in the 2-position. Therefore, the benzoyl derivative 4b was prepared by condensing amino alcohol 3 with phenylglyoxal. 

The polymer-bound catalysts A-C. (Table 31) are prepared by reaction of the corresponding amino alcohols with partially chloromethylated 1 -2% cross-linked polystyrene. In the case of A, the enantioselectivity of the addition of dialkylzincs to aldehydes is higher than with the corresponding monomeric ephedrine derivatives (vide supra). Interesting insights into the mechanism of the alkylation of aldehydes by dialkylzinc reagents can be obtained from the experi-... 

The addition of 2-propenyltris(diethylamino)titanium to 2-(dibenzylamino)alkanals, readily prepared from amino acids, yields the anti-amino alcohols with high stereoselectivity and free of racemization91. Allylsilanes, with Lewis acids under the conditions of chelation control, lead to the iyn-diastereomers91. 

Another example of reagent-induced asymmetric synthesis is the enantioselective preparation of phosphoramides 6 by addition of dialkylzine reagents to A-diphenylphosphinoylimincs 4 in the presence of the enantiomerically pure 1,2-amino alcohols 5a or 5 b (diethylzinc does not add to A-silyl- or A-phenylimines)12. Phosphoramides 6 (crystalline solids) are obtained in moderate to good yield and good enantioselectivity. The latter can be enhanced by recrystallization. Acidic hydrolysis with dilute 3 M hydrochloric acid/tetrahydrofuran provides the corresponding amines 7 without any racemization. 

A variety of chiral amides as well as oxazolidones388 and imidazolidones389,390 may easily be prepared from amino alcohols that are derived from amino acids391 392. The addition of the lithium enolates of these amides under kinetically controlled conditions to a,/i-unsaturated esters yields optically active pentanedioates. Both syn- and //-5-amino-5-oxopcntanoates may be obtained with good diastereomeric ratios192. 

Several methods for asymmetric C —C bond formation have been developed based on the 1,4-addition of chiral nonracemic azaenolates derived from optically active imines or enamines. These methods are closely related to the Enders and Schollkopf procedures. A notable advantage of all these methods is the ready removal of the auxiliary group. Two types of auxiliaries were generally used to prepare the Michael donor chiral ketones, such as camphor or 2-hydroxy-3-pinanone chiral amines, in particular 1-phenylethanamine, and amino alcohol and amino acid derivatives. 

Another approach for the synthesis of enantiopure amino acids or amino alcohols is the enantioselective enzyme-catalyzed hydrolysis of hydantoins. As discussed above, hydantoins are very easily racemized in weak alkaline solutions via keto enol tautomerism. Sugai et al. have reported the DKR of the hydantoin prepared from DL-phenylalanine. DKR took place smoothly by the use of D-hydantoinase at a pH of 9 employing a borate buffer (Figure 4.17) [42]. 

The reaction between epoxides and ammonia is a general and useful method for the preparation of P-hydroxyamines. " Ammonia gives largely the primary amine, but also some secondary and tertiary amines. The useful solvents, the ethanolamines, are prepared by this reaction. For another way of accomplishing this conversion, see 10-54. The reaction can be catalyzed with Yb(OTf)3 and in the presence of a-BINOL is l,l -bi-2-naphthol derivative gives amino alcohols with high asymmetric induction. A variation used Yb(OTf)3 at lOkbar or at ambient pressure. Lithium triflate can also be used. Primary and secondary amines give, respectively, secondary and tertiary amines, for example. 

P-Amino alcohols can be prepared by treatment of an alkene with a reagent prepared from HgO and HBF4 along with aniline to give an ami nomercurial... 

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