The Direct and Enantioselective Organocatalytic α-Oxidation of Aldehydes

Brown, Sean P.; Brochu, Michael P.; Sinz, Christopher J.; MacMillan, David W. C.

doi:10.1021/ja037096s

Cited by 522 publications

(177 citation statements)

References 17 publications

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“…After various chiral carboxylic acids and chiral alcohols were assayed, we found that not only did the use of 1-(1-naphthyl)glycolic acid as a catalyst in Et 2 O proceed O-NA reaction in excellent enantioselectivity (Scheme 10), but also the use of TADDOL derivative promoted enantioselective N-NA reaction (Scheme 11). 16 Recent advances of the reactions using proline or its analogs as a catalyst are highlighted in organic chemistry. The asymmetric O-NA reaction catalyzed by proline or its analogs has been reported by several groups.…”

Section: Catalytic Enantioselective Nitroso Aldol Reactionmentioning

confidence: 99%

Nitroso and Azo Compounds in Modern Organic Synthesis: Late Blooming but Very Rich

Yamamoto

Kawasaki

2007

Bulletin of the Chemical Society of Japan

161

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The catalytic enantioselective oxidation is an extremely important process in organic synthesis and numbers of effort to improve this process have been reported so far. Although nitroso and azo compounds are attractive tools for hydroxylation and amination of organic compounds, no reports on a catalytic asymmetric version of these reactions had been reported until recently. The main issues were their high and unique reactivities. In this review, we would like to introduce the recent advances in this area.

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Section: Catalytic Enantioselective Nitroso Aldol Reactionmentioning

confidence: 99%

Nitroso and Azo Compounds in Modern Organic Synthesis: Late Blooming but Very Rich

Yamamoto

Kawasaki

2007

Bulletin of the Chemical Society of Japan

161

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“…N-Boc-cyclohexylglycine 34 was synthesized in three straightforward steps. First, the N-PMP group of ent-25 was removed oxidatively by using PhI(OAc) 2 and the resulting amine was protected in situ with Boc 2 O and Ac 2 O in the presence of aqueous Na 2 CO 3 affording 30 and 31 in 68% and 64% yield, respectively. [14] Second, removal of the keto functionality present in 30 was accomplished by its treatment with tosylhydrazine in refluxing methanol and subsequent reduction of the intermediate hydrazone with NaBH 4 provided N-Boc-protected ethyl cyclohexylglycinate 33 in 50% overall yield.…”

Section: Full Papersmentioning

confidence: 99%

“…[1,2] Mechanistically, these reactions are based as the catalytic activation of one reaction partner to an enamine or iminium intermediate; the intermediate subsequently reacts in a highly stereospecific manner to form a new carbon-carbon bond and one or more stereocenters. Herein, we disclose our findings on the catalytic asymmetric Mannich-type reaction using ketones as donors that reveal some interesting aspects distinctly different from those of the parent aldol reaction.…”

Section: Introductionmentioning

confidence: 99%

The Scope of the Direct Proline‐Catalyzed Asymmetric Addition of Ketones to Imines

et al. 2004

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A full account of catalytic direct asymmetric Mannich-type reactions is presented describing the scope of amino acid-catalyzed additions of unmodified ketones to a large variety of imines. These reactions are performed under very mild, operationally simple, and environmentally friendly and benign conditions employing a one-pot, three-component protocol as well as preformed imines. Typically, products were obtained with high regio-and diastereoselectivities and excellent enantioselectivities. The methodology developed was applied as a powerful approach toward the synthesis of enantiomerically pure functionalized a-amino acids, g-lactones, oxime-functionalized amino acids as well as pharmacologically important targets such as (R)-cyclohexylglycine.

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“…One unusual feature is a striking temporal increase in reaction rate that is observed in the α-aminoxylation [7,8] (eq 1a) and α-amination of aldehydes [9,10] (eq 1b), but is not observed in aldol reactions (eq 1c). In addition, additives including acids and bases have been observed to influence reactions employing proline as well as other pyrrolidine-based catalysts [11,12].…”

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confidence: 99%

A Coherent Mechanistic Rationale for Additive Effects and Autoinductive Behaviour in Proline‐Mediated Reactions

et al. 2009

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Abstract. Differences in the kinetic behavior of aldol reactions compared to aminoxylation and amination reactions are rationalized by consideration of the ratedetermining step in each case. Both autoinductive behavior and the rate-enhancing effect of additives are attributed to an effect on the enamine formation step.Keywords: organocatalysis · kinetics · autoinduction · amino acid catalysis · reaction mechanism Proline catalysis, elegantly revived by List, Lerner and Barbas in 2000 [1], has demonstrated efficient and enantioselective carbon-carbon and carbonheteroatom bond-forming reactions, including those shown in eq. 1, and has inspired the development of many other catalysts for a myriad of selective transformations [2]. Computational studies [3] have suggested a mechanistic analogy to reactions of aldolase enzymes [4]. Our recent work provided the first kinetic support for the enamine mechanism in aldol reactions and clarified the role of water on and off the catalytic cycle [5,6].(1a) (1b) (1c)A number of intriguing experimental observations have yet to be rationalized for these reactions. One unusual feature is a striking temporal increase in reaction rate that is observed in the α-aminoxylation [7,8] (eq 1a) and α-amination of aldehydes [9,10] (eq 1b), but is not observed in aldol reactions (eq 1c). In addition, additives including acids and bases have been observed to influence reactions employing proline as well as other pyrrolidine-based catalysts [11,12]. Here we present kinetic results that offer a coherent mechanistic rationalization for both the role of additives and the autoinductive behavior in proline-mediated reactions. These findings suggest an important role for detailed kinetic analysis in understanding and improving catalyst efficiency.The autoinductive behavior observed in the reactions of eqs 1a and 1b suggests that the product plays a role in accelerating rate, as is confirmed in Figure 1 for addition of product 3b to the α-amination reaction of eq 1b. The figure also shows that addition of aldol product 7 to the aldol reaction of eq 1c has no influence on the rate of this reaction. 2The two reactions exhibit distinctly different kinetic profiles, with the aldol reaction characterized by well-behaved positive order kinetics while the reactions of eqs 1a-1b show the sigmoidal conversion profile characteristic of an autoinductive process. Product ee is unaffected by added product in either reaction. The reactions of eqs. 1a and 1b do not proceed in the in the presence of product and absence of proline, confirming that the reactions are productaccelerated, or autoinductive, but not truly autocatalytic [14]. Careful studies, including those using fully soluble proline derivatives, showed that the effect could not be attributed to increasing solubilization of proline as the reaction proceeds [13].Interestingly, however, our further studies show that the source of the rate enhancement in the reactions of eqs 1a and 1b is not limited to the product specific to that reaction: Figure 2 show...

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The Direct and Enantioselective Organocatalytic α-Oxidation of Aldehydes

Cited by 522 publications

References 17 publications

Nitroso and Azo Compounds in Modern Organic Synthesis: Late Blooming but Very Rich

Nitroso and Azo Compounds in Modern Organic Synthesis: Late Blooming but Very Rich

The Scope of the Direct Proline‐Catalyzed Asymmetric Addition of Ketones to Imines

A Coherent Mechanistic Rationale for Additive Effects and Autoinductive Behaviour in Proline‐Mediated Reactions

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