A Practical, efficient, and atom economic alternative to the Wittig and Horner–Wadsworth–Emmons reactions for the synthesis of (E)-α,β-unsaturated esters from aldehydes

List, Benjamin; Doehring, A.; Fonseca, M.; Job, Andreas; Rios, Ramón

doi:10.1016/j.tet.2005.09.081

Cited by 66 publications

(42 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The thermodynamically less stable β,γ-unsaturated ester 9 was formed as a result of the aldol reaction between the α-sulfonyl carbanion of 4 and phenylacetaldehyde followed by double bond isomerization. [22] Scheme 4. Synthesis of the α-sulfonyl ester 9 from BTFP sulfone 4 and phenylacetaldehyde.…”

Section: Resultsmentioning

confidence: 99%

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

et al. 2008

View full text Add to dashboard Cite

The 3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones tert-butyl α-(BTFPsulfonyl)acetate (4) and Weinreb α-(BTFPsulfonyl)-acetamide (5) have successfully been employed in the JuliaKocienski olefination of aldehydes with K 2 CO 3 as the base at 120°C in DMF under solid/liquid phase-transfer catalysis conditions to afford α,β-unsaturated esters and Weinreb amides, respectively. The corresponding products were obtained in good yields and with high E stereoselectivities (E/Z up to Ͼ99:1), especially in the case of the amides. A detailed computational study of the Julia-Kocienski olefination with BTFP sulfone 4 was carried out and confirmed the existence of an equilibrium in the initial addition of the sulfone enolate

show abstract

Section: Resultsmentioning

confidence: 99%

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

et al. 2008

View full text Add to dashboard Cite

show abstract

“…They have been frequently applied to synthesis of a variety of significant pharmaceuticals and natural products. [2][3][4][5][6][7][8][9][10][11][12][13] However, their commercial availability is still limited and quite expensive, and they are more commonly available as the corresponding potassium salts. In particular, monomethyl malonate became commercially available only last year, but is expensive, or the purities are typically less than 99%, such as 96%.…”

mentioning

confidence: 99%

Practical Large Scale Synthesis of Half-Esters of Malonic Acid

Niwayama

Cho

2009

Chem. Pharm. Bull.

View full text Add to dashboard Cite

Half-esters of malonic acid such as monomethyl malonate and monoethyl malonate are very important building blocks. They have been frequently applied to synthesis of a variety of significant pharmaceuticals and natural products. [2][3][4][5][6][7][8][9][10][11][12][13] However, their commercial availability is still limited and quite expensive, and they are more commonly available as the corresponding potassium salts. In particular, monomethyl malonate became commercially available only last year, but is expensive, or the purities are typically less than 99%, such as 96%. Therefore, development of a more efficient synthetic method for monoalkyl malonates on a large scale is essential.One method for preparation of half-esters is monosaponification of symmetric diesters, but successful distinction of the two identical ester groups remains challenging. In fact, monosaponification typically produces a dirty mixture of the starting diester, the corresponding halfester, and the diacid, even with the use of one equivalent of a base. In particular, the synthesis of half-esters of malonic acid is still difficult especially on a large scale, because of potential decarboxylation. Only a limited number of examples of monosaponification of dimethyl or diethyl malonate have been reported, [14][15][16] but they require a long time and more than one step. Some modified methods are reported applying Meldrum's acid, 17,18) but Meldrum's acid is costly and not suitable for large-scale production of monoalkyl malononate. The enzymatic monohydrolysis of dialkyl malonates reported utilizes an enzyme not commercially available. 19) Other methods by carbalkoxylation of malonic acid are also reported, but the yields are rather modest. 20)Herein we describe a large-scale synthesis of monomethyl malonate and monoethyl malonate applying the selective monohydrolysis of symmetric diesters we reported before. Earlier, we reported a selective monohydrolysis that enables a series of symmetric diesters with the use of an aqueous NaOH or KOH and a co-solvent such as tetrahydrofuran (THF) or CH 3 CN at 0°C (Chart 1).21) This reaction is practical, mild, and environmentally benign, and has been of interest in process chemistry, exhibiting the potential of scaling up. The selectivity of this reaction was initially found to be particularly high for cyclic 1,2-diesters with the two ester groups in close proximity, even with the use of almost 2 equivalents (or greater) of the base, producing the corresponding half-esters in near-quantitative yields. We reasoned that electrostatic attractive interaction between the two closely located carbonyl groups may play a role in this high selectivity. We recently modified the conditions of this reaction and applied them to monohydrolysis of a series of dialkyl malonates and their derivatives on the scale of 1.2 mmol. 22) They show that the yields are around 80% to near quantitative. Here we examined the possibility of scaling up this reaction, focusing on monomethyl malonate and monoethyl malonate, which are among...

show abstract

“…Synthesis of optically active 1,4-bis (2,2-difluoro-3-(hydroxymethyl)cyclopropyl)benzene (5) using chemo enzymatic reaction Synthesis of a racemic and DL mixture of gem-difluorocyclopropane 5 was accomplished following Scheme 1. (E,E)-Diene 7 was prepared using terephthaldicarboxaldehyde as a starting material by Horner-Wadsworth-Emmons reaction in 93% yield [6], and subsequent diisobutylalminum hydride (DIBAL) reduction of the ethoxycarbonyl groups of 7 to give 1,4-bis((E)-2-hydroxy-1-propenyl)benzene (8) in 86% yield [7]. We initially prepared benzyl ether derivative 9 (R = Benzyl) and converted it to the gem-difluorocyclopropane; the corresponding gem-difluorocyclopropane was obtained in excellent yield, however, we soon recognized that benzyl ether was not appropriate for the protecting group because significant decomposition of the difluorocyclopropane moieties took place during the de-protection step of the benzyl group by hydrogenation.…”

Section: Resultsmentioning

confidence: 99%

gem-Difluorocyclopropane as core molecule candidate for liquid crystal compounds

Itoh

Kanbara

Ohashi

et al. 2007

Journal of Fluorine Chemistry

View full text Add to dashboard Cite

A Practical, efficient, and atom economic alternative to the Wittig and Horner–Wadsworth–Emmons reactions for the synthesis of (E)-α,β-unsaturated esters from aldehydes

Cited by 66 publications

References 43 publications

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

Practical Large Scale Synthesis of Half-Esters of Malonic Acid

gem-Difluorocyclopropane as core molecule candidate for liquid crystal compounds

Contact Info

Product

Resources

About