Highly Stereoselective Aldol Reactions of Titanium Enolates from Lactate-Derived Chiral Ketones

Solsona, Joan G.; Romea, Pedro; Urpı́, Fèlix; Vilarrasa, Jaume

doi:10.1021/ol0274054

Cited by 48 publications

(24 citation statements)

References 22 publications

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“…The consequences are particularly apparent in the field of diastereoselective synthesis. Application of oxazolidinones as chiral auxiliaries leads to aldol products with high diastereoselectivity; however, the stereochemical outcome of the synthesis depends on the enolate formation step 13. Thus, titanium(IV)‐ ate enolates furnish Evans syn aldols whereas neutral trichlorotitanium enolates form non‐Evans syn aldols, presumably through highly ordered chelated transition states 14.…”

Section: Preparation Methods For and Structure Investigations Into Timentioning

confidence: 99%

Titanium Enolate Chemistry at the Beginning of the 21st Century

2016

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Section: Preparation Methods For and Structure Investigations Into Timentioning

confidence: 99%

Titanium Enolate Chemistry at the Beginning of the 21st Century

2016

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“…Urpí and coworkers also studied the titanium-mediated syn aldol process using ketone 77 ( [37]. An increased selectivity and decreased yield were observed when using 2 equiv of TiCl 4 (condition B) [38].…”

Section: 4-asymmetric Induction Using α-Alkoxy Ketonesmentioning

confidence: 99%

“…This selectivity improved greatly for alkyl aldehydes when the aldol reaction was conducted in the presence of 1.1 equiv of DME (1,2-dimethoxyethane). The mechanistic details that explain the selectivity inversion of these reactions are still a challenge to determine; however, there is strong evidence that the diastereoisomeric Ti-enolate complex plays a major role in the transition states of this process (Table 5.3) [37].…”

Section: 4-asymmetric Induction Using α-Alkoxy Ketonesmentioning

confidence: 99%

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Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

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The selectivity of aldol reactions involving kinetic enolates is related to various factors such as the nature of the Lewis acid (Li, Mg, B, Al, Ti, Sn, etc.), the presence of stereogenic centers in both the substrates and reagents, the nature of their substituents and the reaction conditions. Another factor of major importance is the nature of the enolate double bond (Z or E) [1].In general, it is well known that in aldol reactions involving metal enolates, which proceed through a six-membered cyclic transition state, the Z-enolate leads to the formation of 1,2-syn aldol adducts and the E-enolate affords aldol adducts with the 1,2-anti configuration. A rationalization for the observed selectivities of these aldol reactions was proposed by Zimmerman and Traxler (Scheme 5.1) [2]. According to this model, the nature of the double bond geometry plays a primary role in determining the energies of the competing transition states. For Z-enolates, the transition state TS2 is more destabilized than transition state TS1 because of the 1,3-diaxial interactions between the R 1 and R 3 substituents as well as between these substituents and one of the metal ligands (L). Therefore, the Z-enolate preferentially leads to the formation of the 1,2-syn aldol adduct.For the E-enolate, 1,3-diaxial interactions between the R 1 and R 3 substituents and between both R 1 and R 3 and one of the metal ligands are present in transition state TS4. Therefore, the 1,2-anti aldol adduct is obtained from the lower energy transition state TS3.Modern aldol reactions use preformed enolates to obtain good yields by preventing side reactions. This methodology has proven to be very effective for various Lewis acids derived from lithium, titanium, tin, and boron. By using preformed enolates with chiral substrates and reagents, it is possible to obtain aldol adducts with an excellent degree of asymmetric induction.The IUPAC defines asymmetric induction as the traditional term describing the preferential formation in a chemical reaction of one enantiomer (or diastereomer) over the other as a result of a chiral feature present in the substrate, reagent, catalyst, or the environment [3].

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“…Highly stereoselective aldol reactions have been developed using the titanium or zirconium enolates containing chiral auxiliary since 1990 (24)(25)(26)(27)(28)(29). Because of the excellent binding ability of titanium and zirconium, the Lewis acidity of the titanium or zirconium metal center can be easily manipulated by variation of chiral ligand attached to titanium, which leads to obtain high levels of diastereofacial selectivity in appropriate cases (30).…”

Section: Transition Metals Based Lewis Acidsmentioning

confidence: 99%

Aldol Reaction—Homogeneous

Cai

2011

Encyclopedia of Catalysis

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The aldol reaction is one of the oldest and important methods for the construction of carbon–carbon bonds in organic chemistry. Over the last 30 years, tremendous efforts have resulted in the development of many highly sophisticated and efficient catalytic methods of modern aldol reactions in catalytic chemo‐, regio‐, enantio‐, and diastereoselective manners. This review outlined those efforts in homogeneous catalysis and discussed with selected examples (331 publications) according to the different elemental types of catalysts, for example, transition metals and rare earth metals based Lewis acids, main group metals based catalysts, multifunctional catalysts, and metal‐free catalysts.

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Highly Stereoselective Aldol Reactions of Titanium Enolates from Lactate-Derived Chiral Ketones

Cited by 48 publications

References 22 publications

Titanium Enolate Chemistry at the Beginning of the 21st Century

Titanium Enolate Chemistry at the Beginning of the 21st Century

Asymmetric Induction in Aldol Additions

Aldol Reaction—Homogeneous

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