Catalytic Asymmetric Aminohydroxylation with Amino-Substituted Heterocycles as Nitrogen Sources

The suprafacial, vicinal addition of a heterocyclic moiety and a hydroxyl group is achieved by the osmium-catalyzed asymmetric aminohydroxylation (AA) of olefins with amino-substituted heterocycles as the nitrogen sources. Amino alcohols are obtained in up to 97 % yield and with up to 99 % ee when a ligand derived from dihydroquinidine (DHQD-L) is used [Eq. (1); Rⁱ indicates the remaining portion of the heterocycle (Het); H₂O is the O source]. The AA can now be considered as a means to directly introduce complex, biologically relevant substructures to hydrocarbon backbones.     

A DFT study of the enantioselective reduction of prochiral ketones promoted by pinene-derived amino alcohols

Recently, a pinene-derived amino alcohol [(1R,2R,3S,5R)-3-amino-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol] has been experimentally employed as an effective chiral catalytic precursor in the borane-mediated asymmetric reduction of prochiral ketones to produce the corresponding secondary alcohols, which provides the products in 96% ee. In this paper, we suggest a mechanism for this reduction process and then theoretically investigate it in detail by density functional theory. Fully geometry-optimized reactants, products, transition structures, and intermediates were obtained at the B3LYP/6-31G (d,p) level, and the results reveal that this reaction has five steps. Further calculations show that the solvent effect of THF has no great influence on the enantioselectivity of this reduction.     

Organolithium-induced enantioselective alkylative double ring-opening of epoxides: synthesis of enantioenriched unsaturated amino alcohols

The use of (−)-sparteine as an external chiral ligand in enantioselective organolithium-induced alkylative double ring-opening of dihydropyrrole epoxides and 7-azanorbornene-type epoxides gives unsaturated acyclic amino alcohols, and amino cyclohexenols in up to 87% ee.     

Copper-catalyzed enantioselective addition of alcohols to isatin-derived ketimines

The first copper-catalyzed enantioselective addition of alcohols to imines was described. In the presence of 1?mol% Cu(OAc)₂ complexed with chiral cyclohexane-based N,P-ligand L4, chiral isatin-derived N,O-aminals were obtained in excellent yields (93–99%) and good-to-excellent enantioselectivities (up to 93% ee) under mild conditions.     

Catalytic enantioselective allylboration of propargylic aldehydes

Homoallylic propargylic alcohols are important building blocks in natural product synthesis. This moiety can be transformed into various other structures by performing other known transformations, which can in turn lead to the synthesis of biologically useful compounds. Herein, a methodology based on Lewis acid assisted Brønsted acid catalysed allylboration of propargylic aldehydes is described. A detailed optimization study followed by a thorough examination of substrate scope have been explored.     

Detailed studies on the reduction of aliphatic 3-, 4-, 6-, and 13-oximino esters: Synthesis of novel isomeric amino esters,oximino alcohols,and amino alcohols

The preparation of novel 3-, 4-, 6-, and 13-amino-tetradecanoic acid methyl esters (2a–d) obtained by the reduction of 3-, 4-, 6-, and 13-oximino-tetradecanoic acid methyl esters (1a–d), was investigated. Oximino esters were reduced to afford the corresponding amino esters using NaBH₄–ZrCl₄ reducing system with good yields (58–82%). However, the reduction of oximino esters with LiAlH₄ and BH₃. Tetrahydrofuran gave the corresponding novel 3-, 4-, 6-, and 13-oximino alcohols (3a–d), and 3-, 4-, 6-, and 13-amino alcohols (4a–d) respectively with good chemical yields.     

Asymmetric reduction of ketones with sodium aluminum hydride modified with chiral amino alcohols

Asymmetric reduction of ketones with hydride complexes, which were prepared by in situ modification of NaAlH₄, with various chiral amino alcohols or diamines, was studied. The highest enantioselectivity (up to 93% ee) was achieved using 2-(hydroxydiphenylmethyl)pyrrolidine as a chiral inducing agent.     

Catalytic enantioselective borane reduction of aromatic ketones with sulfonyl (S)-prolinol

The asymmetric reduction of aromatic ketones was catalyzed by a class of recoverable and highly stable chiral sulfonamides derived from (S)-proline to yield optically active secondary alcohols in high yields and with enantiomeric excesses of up to 91%.     

Rhodium(I)-catalyzed enantioselective 1,4-addition of nucleophilic silicon

A rhodium(I)-catalyzed activation of a silicon-boron linkage, that is, the transmetalation of silicon from boron to rhodium(I) by means of an Rh^I-OH complex, enables the conjugate transfer of nucleophilic silicon onto α,β-unsaturated acceptors. Pre- or in situ formed cationic rhodium(I)-binap complexes catalyze this novel carbon-silicon bond formation with exceptional enantiocontrol, 92 to >99% ee for cyclic carbonyl and carboxyl compounds as well as >99% ee for acyclic carboxyl compounds.     

Sharpless Asymmetric Aminohydroxylation: Scope,Limitations, and Use in Synthesis

As a valuable methodology for organic synthesis , asymmetric aminohydroxylation (AA)—the catalytic and asymmetric conversion of alkenes into enantiomerically enriched N‐protected amino alcohols—has become established in a remarkably short period of time. Examples of the types of products that can be synthesized easily on a reasonably large scale and in enantiomerically pure form are shown in the picture.     

Palladium-catalyzed asymmetric synthesis of allylic alcohols from unsymmetrical and symmetrical racemic allylic carbonates featuring C-O-bond formation and dynamic kinetic resolution

Described is the asymmetric synthesis of the allylic alcohols 11 (85% ee), 15 (99% ee), 17 (93% ee), 19 (61% ee), and 21 (69% ee) through a Pd-catalyzed reaction of the unsymmetrical carbonates rac-10, rac-12, rac-14, rac-16, rac-18, and rac-20, respectively, with KHCO₃ and H₂O in the presence of bisphosphane 6. Similarly the allylic alcohols 23 (99% ee) and 25 (97% ee) have been obtained from the symmetrical carbonates rac-22 and rac-24, respectively. Reaction of the meso-biscarbonate 26 with H₂O and Pd(0)/6 afforded alcohol 27 (96% ee), which was converted to the PG building block 32. The unsaturated bisphosphane 33 showed in the synthesis of alcohols 36, 37, and 39 a similar high selectivity as 6. The formation of alcohols 11, 15, and 17 involves an efficient dynamic kinetic resolution.     

Highly enantioselective addition of linear alkyl alkynes to linear aldehydes

It is discovered that the use of biscyclohexylamine (Cy₂NH) as an additive can greatly enhance the enantioselectivity for the reaction of linear alkyl alkynes with linear aldehydes. The combination of (S)-BINOL (20 mol %), Cy₂NH (5 mol %), ZnEt₂ (2 equiv), and Ti(OⁱPr)₄ (0.5 equiv) catalyzes the reaction at room temperature in diethyl ether solution with 81-89% ee and 57-77% yield.     

Catalytic,Enantioselective Synthesis of α-Aminonitriles with a Novel Zirconium Catalyst

Strecker reactions of aldimines with Bu₃SnCN in the presence of the novel chiral zirconium binuclear catalyst 1 provide α-aminonitriles in good yields and with high enantioselectivities. The reaction can be applied to a wide range of substrates. Since both enantiomers of the chiral sources are readily avaibable, both enantiomers of the α-aminonitriles are easily prepared according to this method. L=N-methylimidazole.     

Catalytic enantioselective addition of diethylzinc to (hetero)aromatic aldehydes

The asymmetric alkylation with diethylzinc of five heterocyclic aldehydes and benzaldehyde (for comparison) has been studied in the presence of two optically active amino alcohols: (S)-2-amino-1-butanol (AB) and (1S,2R)-N,N-dibutylnorephedrine (DBNE). A number of chiral (hetero)aromatic secondary alcohols were synthesized in high yields (95–98%) with enantioselectivity up to 92% enantiomeric excess (ee) in the presence of DBNE catalyst. Optically active thienyl and 4-pyridyl derivatives were prepared for the first time by catalytic asymmetric alkylation. The influence of the amount of DBNE on the enantioselectivity was investigated. In contrast to benzaldehyde, 2-furan- and 2-thiophene-carbaldehydes, in the case of 3- and 4-pyridinecarbaldehydes the ee values depend directly on the catalyst concentration. © 1998 John Wiley & Sons, Ltd.     

Asymmetric alkylation of aromatic aldehydes with dialkylzinc catalyzed by novel amino derivatives of hydroxytetrahydropyran

Novel, specially prepared, tetrahydropyran‐based γ‐amino alcohols (S)‐2‐(aminomethyl)‐3‐hydroxy‐6‐ethoxy(phenoxy)‐tetrahydropyrans ( I ) (amino = n‐Bu₂N, piperidinyl, pyrrolidinyl, azetidinyl) were tested as catalysts in the asymmetric addition of Et₂Zn and n‐Bu₂Zn to (hetero)aromatic aldehydes. In most cases the phenoxy derivatives of I acted more enantioselectively than the ethoxy ones. The dibutylamino derivaties showed the least enantioselectivity; the pyrrolidinyl derivatives were more active as catalysts than piperidinyl and azetidinyl compounds. The highest enantioselectivity was observed in the addition of Et₂Zn to benzaldehyde in the presence of (S)‐2‐(N‐pyrrolidinylmethyl)‐3‐hydroxy‐6‐phenoxytetrahydropyran. The corresponding alcohol was prepared with 72% ee (R‐configuration). The addition of dibutylzinc proceeded slowly and less selectively. The alkylation of (hetero)aromatic aldehydes with Et₂Zn and n‐Bu₂Zn was also studied in the presence of the known optical inductor (1S,2R)‐N,N‐dibutylnorephedrine. Some chiral aromatic secondary alcohols were synthesized in high chemical yields and up to 93% ee enantioselectivity. Copyright © 1999 John Wiley & Sons, Ltd.