Amino alcohol with aldehyde

Condensation of [3- or "y-amino alcohols with aldehydes or ketones RR CO gives the product 27. In solution the position of the equilibrium varies with R and R, and with the solvent (73). When the carbonyl reactant is a substituted benzaldehyde, the solid is found (IR, KBr) to comprise molecules of the open-chain structure 27a, whereas aliphatic aldehydes and ketones give crystals of dihydro- 1,3-benzoxazines, 27b. An interesting case is that of the condensation product of o-hydroxybenzylamine with cyclopentanone, for which McDonagh and Smith (73) suggest that ring and chain tautomers coexist in the solid. 

The carbamate derivatives of amino alcohols also proved applicable for the synthesis of cyclic hemiaminal derivatives. Through the ring closures of W-BOC-substituted 1,3-amino alcohols with aldehydes or acetals, 3-BOC-1,3-oxazine derivatives were obtained <1998TL6561, 1999J(P1)1933, 2006JOC8481, 2006T8687, 2006TL7923>. 

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 condensation of enantiomerically pure amino alcohols (derived from amino acids) with aldehydes to furnish 1,3-oxazolidines was studied by Kuhnert and Danks in 2001 (Scheme 6.212) [382], Under solvent-free conditions, microwave irradiation of equimolar mixtures of the amino alcohol and the aldehyde for less than 3 min provided high isolated yields of 1,3-oxazolidines with excellent diastereoselectivity. In the case of (-)-ephedrine, prolonged microwave irradiation (3 min) produced quantitative conversions and high diastereoselectivities. For shorter irradiation times (80 s) mixtures of the two diastereomers were obtained with moderate conversions. 

Racker et al. have developed an interesting new combinatorial method for the synthesis of [l,4]oxazepin-7-ones (eg 139, R = Ph) from aldehydes and a-amino alcohols with the Baylis-Hillman reaction being a key step . 

Pd-catalyzed intramolecular etherification reactions of aliphatic alcohols have also been practiced in tandem with other bond-forming processes, such as a Pd-catalyzed allyltin addition to an aldehyde (Equation (32)).160 Similarly, a tandem C-N and G-O bond formation sequence occurs (Equation (33)) during the reactions of /3-amino alcohols with biscarbonates in the presence of the N,O-acetal-derived ligand 43.161-163... 

Popular oxidation reactions of peptide alcohols such as the Parikh-Doering or Dess-Martin in addition to older oxidation reactions such as Collins, pyridinium chlorochromate, or Swern oxidation afford racemization free productsJ9121415 37-39 Oxidations using pyridinium dichromate results in racemization and low yields of product.[l3 Oxidation reactions have also been utilized in semisynthetic pathways of peptide aldehydes (1) peptide aldehydes are obtained through the enzymatic acylation of a peptide ester to an amino alcohol with subsequent oxidation of the peptide alcohol to afford the aldehyde, and (2) peptide aldehydes can also be obtained by direct enzymatic oxidation of the peptide alcohol by alcohol de-hydrogenaseJ40 41 ... 

Semisynthetic enzymatic oxidation of peptide alcohols employs equine liver alcohol dehydrogenase. Amino alcohols with nonpolar side chains and Z-Om[CH2OH] worked as effective substrates while polar amino alcohols such as H-Arg[CH2OH] and H-Lys[CH2OH] failed as substrates. To attain complete oxidation, semicarbazide was present in the reaction mixture to immediately trap the aldehyde, and flavin mononucleotide was used to oxidize the NADH to NAD+, which serves to oxidize the alcohol 41] Configurational stability was confirmed by NMR spectroscopy as in the case of Ac-Phe[CH2OH], which was prepared by sodium borohydride reduction of Ac-Phe-H 4 1... 

A different semisynthetic method involves the acylation of an amino alcohol with a peptide ester and the resulting amino alcohol is subsequently oxidized to the aldehyde 40 The acylation of H-Phe[CH2OH] with the peptide ester Z-Ala-Ala-Leu-OMe is carried out in 5% DMF/MeCN with the subtilisin distributed on the surface of macroporous silica gel. The resulting peptide alcohol is oxidized under mild conditions using anhydrous dimethyl sulfoxide and 20-fold excess of acetic anhydride with purification via flash chromatography 40] Z-Phe[CH2OH] has been oxidized under these conditions and the optical rotation indicates little epimerization as compared to literature values 11 40 ... 

In an alternative route,2 Boc-protected amino acids are reduced to the protected amino alcohol with borane-THF (45-95% yield) and pyridinium dichromate is used for oxidation to the aldehyde (75-90% yield). The optical rotations of the aldehydes obtained by these two procedures differ considerably, presumably owing to racemization encountered in the PDC oxidation. 

The enaminones are hydrogenated to y-amino alcohols with marked stereoselectivity. Ene reactions of aldehydes with -alkenes. Ethylaluminum dichloride in CHjCl,... 

Optically active ferrocene derivatives, particularly ferrocenyl phosphines, have hitherto been utilized as chiral ligands for a wide range of asymmetric synthesis. We have now revealed that the ferrocene moiety can easily be incorporated in amino alcohol ligands instead of phosphinic ligands. The preparative methods for several types of ferrocenylamino alcohols were developed and they were successfully used to catalyze enantioselective addition of dialkylzinc to aldehydes with high enantio-selectivity. In particular, 1,2-disubstituted ferrocenyl amino alcohols with planar... 

The InI-Pd(0)-promoted allylation of aldehydes with N-activated vinylaziridines or allylic acetates proceeds with regio- and stereoselectivity, irrespective of the chirality of the allylic carbon bearing the vinyl group, to provide sy ,syn-2-vinyl-l,3-amino alcohols with three contiguous chiral centers (Scheme 8.64) [90]. In a similar manner, 2-ethynyl-l,3-amino alcohols are synthesized from 2-ethynylaziridines (Scheme 8.65) [91]. 

The traditional method for preparing oxazolidines is to heat a mixture of amino alcohol and aldehyde in a solvent such as benzene with removal of water. A milder procedure that affords some products in high yield when they would otherwise be obtained in only trace amounts is to dehydrate the same mixture with molecular sieves in methylene chloride at room temperature <89JHC1687>. A method that has been effective with amino sugar derivatives is to cyclize with dibromomethane under phase transfer conditions <93Mi 304-02>. 

With optically active amino alcohols and aldehydes, a mixture of diastereomers generally results. For N—H oxazolidines, the ratio of isomers is about 2 1, and for N—Me or N—Pr analogues the ratio is about 9 1. For A-tosyl derivatives, however, diastereomerically pure 2,4-cw-oxazolidines are isolated <92H(33)28i>. Trans isomers (189) are obtained in ratios >10 1 from the zinc chloride or trimethylsilyl triflate-catalyzed reaction of 2-methoxy-oxazolidines with allyltrimethylsilane or... 

Numerous procedures have been reported for the synthesis of iV-protected-a-amino aldehydes [78]. The A-protected a-amino aldehydes can be prepared either by oxidation of the corresponding A-protected j8-amino alcohols with oxidants such as pyridinium dichromate [79,80] or SOs-pyridine-di-methyl sulfoxide (DMSO) [81] or under Swem conditions [DMSO-oxalyl chloride-A,A-diisopropylethylamine (DIEA)] [81-83], by reduction of esters with diisobutyl aluminum hydride (DIBAL) [84], by reduction of A,A-disubstituted amides [85-87], by reduction of urethane-protected A-carboxy-... 

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