Chiral N,N-dialkylnorephedrines as catalysts of the highly enantioselective addition of dialkylzincs to aliphatic and aromatic aldehydes. The asymmetric synthesis of secondary aliphatic and aromatic alcohols of high optical purity

Soai, Kenso; Yokoyama, S.; Hayasaka, Tomoiki

doi:10.1021/jo00013a035

Cited by 234 publications

(71 citation statements)

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“…Triphenylbismuthane (Ph 3 Bi) and dimethylzinc (Me 2 Zn) were mixed in toluene/hexane, and the mixture was heated at reflux for 10 h. The resulting mixed Ph 3 Bi/ Me 2 Zn reagent was treated with various aldehydes in the presence of chiral β-amino alcohol catalysts at 0°C. As shown in Table 1, the reaction of p-tolualdehyde (1a) and Ph 3 Bi/Me 2 Zn in the presence of (1S,2R)-N,N-dibutylnorephedrine (DBNE) [10] gave chiral diaryl methanol 2a with 93 % ee in 96 % yield. Me 2 Zn seems to be a suitable dialkylzinc reagent in this case.…”

Section: Resultsmentioning

confidence: 99%

A Highly Enantioselective and Catalytic Aryl Transfer Reaction Using Mixed Triarylbismuthane and Dialkylzinc Reagents

2007

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Section: Resultsmentioning

confidence: 99%

A Highly Enantioselective and Catalytic Aryl Transfer Reaction Using Mixed Triarylbismuthane and Dialkylzinc Reagents

2007

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“…Oxidation of 21 with SO 3 ⅐pyridine gave the corresponding aldehyde in 91% yield (34). Treatment of this aldehyde with diethylzinc in the presence of (Ϫ)-N,Ndibutylnorephedrine then gave the C(21) alcohol 22 as a 9:1 mixture of diastereomers in 94% yield (35)(36)(37). Protection of alcohol 22 as the triethylsilyl ether proceeded in 94% yield.…”

Section: Chemistrymentioning

confidence: 99%

Total synthesis of (–)-spinosyn A

Mergott

Frank

Roush

2004

Proc. Natl. Acad. Sci. U.S.A.

127

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A convergent, highly stereoselective total synthesis of (؊)-spinosyn A (1) is described. Key features of the synthesis include the transannular Diels-Alder reaction of macrocyclic pentaene 11 and the transannular Morita-Baylis-Hillman cyclization of 12 that generates tetracycle 26. The total synthesis of (؊)-spinosyn A was completed by a sequence involving the highly ␤-selective glycosidation reaction of 13 and glycosyl imidate 30.T he spinosyns are a family of polyketide natural products that possess extraordinary insecticidal activity. The biosynthetic mixture, generated by Saccharopolyspora spinosa, comprises mostly spinosyn A (1) (Scheme 1) (Ϸ85%) and spinosyn D (Ϸ10-15%) (1-8). This mixture is currently marketed for use as an insecticide against a variety of insects (6). Total syntheses of spinosyn A have been reported by Evans and Black (9) and Paquette et al. (10,11). Synthetic StrategyDiels-Alder reactions have been proposed as key steps in the biogenesis of several natural products, including lovastatin, solanapyrone, nargenicin, and ikarugamycin (12). Kirst et al. (3) suggested that the biosynthesis of spinosyn A may involve a transannular Diels-Alder (TDA) (13) reaction of a macrocyclic pentaene to form the C(4)OC(12) and C(7)OC (11) bonds (see 4 3 3; Scheme 1). Kirst also suggested that a transannular cyclization of a 1,3-dicarbonyl nucleophile may generate the C(3)OC (14) bond (3). Alternatively, we speculated that the C(3)OC(14) bond may be formed by a vinylogous Morita-Baylis-Hillman (MBH) reaction mediated by an enzymatic nucleophile (compare 3 3 1; Scheme 1). Based on these biosynthetic considerations, we sought to assemble spinosyn A (1) via a TDA and MBH cyclization sequence of an appropriately functionalized macrocyclic pentaene 4.Diastereoselectivity of the Diels-Alder Reaction. Paramount to the success of this synthetic strategy is the control of the diastereoselectivity of the TDA reaction (4 3 3). It is known from the work of Evans and Black (9) that the intrinsic diastereofacial selectivity of the intramolecular Diels-Alder (IMDA) reaction of 5a favors the incorrect C(7)OC(11) trans-fused diastereomer 6a with 6:1 selectivity (Scheme 2). Although Evans and Black (9) addressed this issue by incorporating a chiral auxiliary (13) in the dienophile (see 5b 3 7b), we would not have recourse to this strategy for the TDA cyclization of 4. Thus, some means for controlling the stereochemistry at the C(7)OC(11) ring fusion relative to the C(9)Oalkoxy substituent in the Diels-Alder reaction was required.We initially hoped to use the steric directing-group strategy to control the diastereoselectivity of the Diels-Alder reaction (15-17), which could involve appending a bromine steric directing group at C(6) of the IMDA or TDA substrate to control the stereochemical outcome of the cycloaddition, leading to the desired C(7)OC(11) trans-fused diastereomer. It was anticipated that TS2, which leads to the undesired C(7)OC(11) trans-fused isomer 10 and is favored in the absence of the C(6)OBr steric direct...

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“…[9][10][11][12][13][14] Some of the chiral b-amino alcohols are natural products, such as cinchonine, cinchonidine, quinine, quinidine, ephedrine, and norephedrine. [15][16][17][18][19][20][21][22] Most of the chiral b-amino alcohols were prepared from camphor derivatives, [23][24][25][26][27] reduction of enantiopure amino acids, 9,[28][29][30] Sharpless' aminohydroxylation of olefins, 31,32 Mannich-type reactions for the direct addition of a-hydroxy ketones to imines, [33][34][35] regioselective ring opening of chiral epoxides and aziridines, 36,37 and nucleophilic addition to a-amino carbonyl compounds and a-hydroxy imines. 38 Preparation of chiral camphor-derived b-amino alcohols has been of interest because they have been successfully used as chiral auxiliaries and ligands in asymmetric syntheses recently.…”

Section: Introductionmentioning

confidence: 99%

Alternative synthetic route to chiral N‐substituted camphor‐derived β‐amino alcohols

2007

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An alternative route from (1R)-(+)-camphor to chiral N-substituted camphor-derived beta-amino alcohol (4b-e) consists of four steps with a total yield of 28%. N-Alkylation of camphor-derived beta-amino alcohol (4a) involves condensation and hydride reduction in one pot without isolation of intermediates. Condensation of 4a with aldehydes or ketones generates a mixture of 1,3-oxazolidines (6) and imino-alcohols (7), which are reduced to 4b-e by NaBH(4).

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Chiral N,N-dialkylnorephedrines as catalysts of the highly enantioselective addition of dialkylzincs to aliphatic and aromatic aldehydes. The asymmetric synthesis of secondary aliphatic and aromatic alcohols of high optical purity

Cited by 234 publications

References 0 publications

A Highly Enantioselective and Catalytic Aryl Transfer Reaction Using Mixed Triarylbismuthane and Dialkylzinc Reagents

A Highly Enantioselective and Catalytic Aryl Transfer Reaction Using Mixed Triarylbismuthane and Dialkylzinc Reagents

Total synthesis of (–)-spinosyn A

Alternative synthetic route to chiral N‐substituted camphor‐derived β‐amino alcohols

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