Efficient Diastereoselective and Enantioselective Nitroaldol Reactions from Prochiral Starting Materials: Utilization of La-Li-6,6'-Disubstituted BINOL Complexes as Asymmetric Catalysts

Sasai, Hiroaki; Tokunaga, Teruhisa; Watanabe, S.; Suzuki, Takayoshi; Itoh, Noriie; Shibasaki, Masakatsu

doi:10.1021/jo00128a005

Cited by 260 publications

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“…2D, side chains of both nitronate and aldehyde occupy equatorial positions. This cyclic six-membered transition state was proposed for the highly synselective asymmetric Henry reactions catalyzed by transition metal complexes (47,48). A chiral guanidine thiourea catalyst is also reported to provide the syn-Henry product (49).…”

Section: Resultsmentioning

confidence: 90%

Organocatalytic asymmetric assembly reactions for the syntheses of carbohydrate derivatives by intermolecular Michael-Henry reactions

Uehara

Imashiro

Hernández‐Torres

et al. 2010

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

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Given the significance of carbohydrates in life, medicine, and industry, the development of simple and efficient de novo methods to synthesize carbohydrates are highly desirable. Organocatalytic asymmetric assembly reactions are powerful tools to rapidly construct molecules with stereochemical complexity from simple precursors. Here, we present a simple and robust methodology for the asymmetric synthesis of pyranose derivatives with taloand manno-configurations from simple achiral precursors through organocatalytic asymmetric intermolecular Michael-Henry reaction sequences. In this process, (tert-butyldimethylsilyloxy)acetaldehyde 1 was successfully utilized in two ways: as a donor in a highly selective anti-Michael reaction and as an acceptor in a consecutive Henry reaction. Varied nitroolefins served as Michael acceptors and varied aldehydes substituted for 1 as Henry acceptors providing for the construction of a wide range of carbohydrates with up to 5 stereocenters. In these reactions, a catalyst-controlled Michael reaction followed by a substrate-controlled Henry reaction provided 3,4-dideoxytalose derivatives 6 in a highly stereoselective manner. The Henry reaction was affected by addition of a simple base such as triethylamine: A complex chiral base was not necessary. 3,4-Dideoxymannose derivatives 7 were produced by simply changing the base from triethylamine to 1,8-diazabicyclo[5.4.0]undec-7-ene. Extension of this methodology to a syn-Michael initiated sequence was also successful. A mechanistic discussion is provided to explain the unusual substrate-induced stereoselectivity of the Henry reaction.amine-thiourea catalyst | asymmetric reaction | carbohydrates | Michael reaction | organocatalysis C arbohydrates are one of the most important classes of organic molecules and play diverse and essential roles in life, medicine, and industry. Since Emil Fischer's structural elucidation and synthesis of carbohydrates more than a century ago (1), carbohydrate synthesis has continued to challenge synthetic chemists. Robust, simple, direct, and highly stereoselective methods to carbohydrate synthesis remain largely elusive and the development of such methodologies is a driving force in synthetic chemistry. Indeed, our discovery of the proline catalyzed intermolecular aldol reaction (2, 3) and other related reactions (4, 5) were made possible by our development of antibody aldolases as synthetic tools for carbohydrate synthesis (6, 7). In the decade since this discovery, organocatalysis has emerged as a promising route to a wide range of chiral molecules (4,5,(8)(9)(10)(11). Our studies in organocatalysis prompted us (5,(12)(13)(14) and later others (15, 16) to develop cascade reactions and one-pot synthetic approaches toward the synthesis of complex molecules containing multiple stereocenters with the aim of producing robust and operationally simple approaches to the synthesis complex asymmetric molecules like carbohydrates. We have classified reactions of this type broadly as organocatalytic asymmetric assembly r...

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Section: Resultsmentioning

confidence: 90%

Organocatalytic asymmetric assembly reactions for the syntheses of carbohydrate derivatives by intermolecular Michael-Henry reactions

Uehara

Imashiro

Hernández‐Torres

et al. 2010

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

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“…syn-Selective reaction can be achieved by a monometallic catalytic system as shown in Fig. 9a, where both an aldehyde and a nitronate coordinate to the metal center to give syn product due to steric repulsion [34][35][36]. To make the reaction proceed in anti-selective manner, different strategy in catalyst design is required [37,38].…”

Section: Anti-selective Catalytic Asymmetric Nitroaldol Reactionmentioning

confidence: 99%

Multimetallic Multifunctional Catalysts for Asymmetric Reactions

Shibasaki

Kanai

Matsunaga

et al. 2011

Bifunctional Molecular Catalysis

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The utility of several types of multimetallic asymmetric catalysts is reviewed. The appropriate design of multidentate chiral ligands provides homobimetallic, heterobimetallic, and polymetallic catalysts upon complexation with metal cations. Cooperative work of multiple catalytically active sites in the asymmetric multimetallic catalysts allows for enhanced catalytic activity and stereoselectivity over monometallic catalysts. Facile systematic tuning of the asymmetric multimetallic catalysts by manipulation of multidentate ligand structure and combination of metal cations enables the generation of diverse set of catalysts having distinct three-dimensional and catalytic properties, boosting the optimization process to identify the best catalyst for a specific reaction of interest.

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“…Y. S. is grateful for a JSPS Research Fellowship for Young Scientists. We thank Dr. Sakamoto (RIKEN) for kindly providing the spectra of synthetic (4S,5R)-epi-cytoxazone (5).…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…[4] Nevertheless, only one report has appeared on highly diastereo-and enantioselective catalytic Henry reactions of nitroalkanes and prochiral aldehydes by Shibasaki et al, utilizing LLB (La-lithium-BINOL) catalyst. [5] As part of our program to develop guanidine-containing organocatalysts, [6] we recently reported on the guanidine-thiourea bifunctional organocatalyst 1 that efficiently catalyzes the Henry reaction with high enantioselectivity.…”

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confidence: 99%

Diastereoselective and Enantioselective Henry (Nitroaldol) Reaction Utilizing a Guanidine‐Thiourea Bifunctional Organocatalyst

2006

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A highly enantio-and diastereoselective Henry reaction of various aldehydes with nitroethane was developed using the guanidine-thiourea bifunctional catalyst 1 (syn selectivity of 86:14 to 99:1 with 84-99 % ee). A variety of nitroalkanes was treated with unbranched and branched aldehydes and gave nitro alcohols with high syn diastereoselectivities (90:10 toThe Henry (nitroaldol) reaction is an important carboncarbon bond-forming reaction which affords valuable synthetic intermediates.[1] Much effort has been made to develop an asymmetric version of this reaction, [2] using prochiral aldehydes and nitromethane in the presence of a chiral metal catalyst [3] or organocatalyst.[4] Nevertheless, only one report has appeared on highly diastereo-and enantioselective catalytic Henry reactions of nitroalkanes and prochiral aldehydes by Shibasaki et al., utilizing LLB (La-lithium-BINOL) catalyst.[5] As part of our program to develop guanidine-containing organocatalysts, [6] we recently reported on the guanidine-thiourea bifunctional organocatalyst 1 that efficiently catalyzes the Henry reaction with high enantioselectivity.[6d] Here, we describe the first example of the organocatalyst 1 catalyzing the Henry reaction with high diastereo-and enantioselectivity. (Figure 1). In the Henry reaction of nitromethane (3a) aldehyde coordinate to the guanidine and thiourea groups [7] in 1, respectively, and the Henry reaction proceeds via the anti-conformational transition state I rather than the gauche conformation II (Figure 2). Therefore, nitro alcohol adducts with (R) configuration were obtained as the major isomer when (S,S)-1 was used. In the case of the Henry reaction with prochiral nitroalkanes (R 2 = alkyl groups etc., Figure 2), the anti conformation of the R 2 group with respect to the carbonyl group of the aldehyde is also considered to be more favorable (conformation I) than the gauche conformation III, and the diastereo-and enantioselectivities of the nitro alcohol adducts are expected to be well controlled, if the reaction proceeds via a transition state similar to that in the reaction with nitromethane (3a). On the basis of these speculations, the diastereo-and enantioselective Henry reaction with the bifunctional organocatalyst 1 was further explored.First, the Henry reaction was examined with 3-phenylpropionaldehyde (2a) and nitroethane (3b) in the presence of (S,S)-1. After optimization of the reaction conditions, [8] the syn-nitro alcohol product (R,R)-4a [9] was obtained with high diastereo-and enantioselectivity (syn/anti = 90:10, 83 % ee) in 76 % yield, by using toluene/aqueous potassium hydroxide (10 mol-%) [10] in the presence of 10 mol-% of catalyst (S,S)-1 at 0°C for 48 h (Scheme 1).The newly generated stereochemistry of the nitro alcohol 4a, i.e. (R,R) configuration, is consistent with the proposed reaction transition state (Figure 2, conformation I). Since the ee value of 4a is much higher than in the case of the Henry reaction with nitromethane (3a) and 2a (55 % ee), [6d] the transition state of t...

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Efficient Diastereoselective and Enantioselective Nitroaldol Reactions from Prochiral Starting Materials: Utilization of La-Li-6,6'-Disubstituted BINOL Complexes as Asymmetric Catalysts

Cited by 260 publications

References 0 publications

Organocatalytic asymmetric assembly reactions for the syntheses of carbohydrate derivatives by intermolecular Michael-Henry reactions

Organocatalytic asymmetric assembly reactions for the syntheses of carbohydrate derivatives by intermolecular Michael-Henry reactions

Multimetallic Multifunctional Catalysts for Asymmetric Reactions

Diastereoselective and Enantioselective Henry (Nitroaldol) Reaction Utilizing a Guanidine‐Thiourea Bifunctional Organocatalyst

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