Asymmetric Synthesis of <i>anti-</i>Aldol Segments via a Nonaldol Route: Synthetic Applications to Statines and (−)-Tetrahydrolipstatin

Ghosh, Arun K.; Shurrush, Khriesto A.; Kulkarni, Sarang

doi:10.1021/jo900642f

Cited by 51 publications

(27 citation statements)

References 91 publications

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“…Of significance is the isolation of the cis a,g-disubstituted g-butyrolactone (52 %i solated yield) as the major product because the cis isomer cannot be prepared by traditional enolate alkylation with an alkyl halide. [16] Forinstance,the alkylation of 11 e with benzyl bromide and LDAa tÀ 78 8 8Cf ormed the thermodynamically more stable trans isomer exclusively.…”

Section: Methodsmentioning

confidence: 99%

A General and Mild Catalytic α‐Alkylation of Unactivated Esters Using Alcohols

Guo

Fang

et al. 2015

Angewandte Chemie

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Catalytic a-alkylation of esters with primary alcohols is ad esirable process because it uses low-toxicity agents and generates water as the by-product. Reported herein is aN CP pincer/Ir catalyst whichi sh ighly efficient for aalkylation of ab road scope of unactivated esters under mild reaction conditions.F or the first time,a lcohols alkylate unactivated a-substituted acyclic esters,l actones,a nd even methyl and ethyl acetates.T his method can be applied to the synthesis of carboxylic acid derivatives with diverse structures and functional groups,s ome of which would be impossible to access by conventional enolate alkylations with alkylh alides.a-Alkylation of esters is one of the most fundamental processes for carbon-carbon bond formation.[1] Thec lassical methods,enolate alkylations,involve the deprotonation of the esters and the addition of the resulting enolate nucleophiles to alkyl halide electrophiles ( Figure 1a).[2] Thenoncatalytic S N 2 substitution reactions are presented in every introductory organic chemistry course.H owever,s uch methods have several crucial limitations:1 )the use of toxic alkylating agents and the formation of inorganic salts as waste;2)competing side reactions,such as enolate eliminations and Claisen condensations,r estrict the substrate scope (e.g., the enolates derived from methyl and ethyl acetates undergo self-condensations readily);and 3) the prerequisite formation of ester enolates typically requires harsh reaction conditions (superbase and low temperature).[1]An alternative,b ut less developed method for a-alkylation of carbonyl compounds is to use alcohols as the alkylating agents.I ndustrially,a lcohols are preferred reagents because they are more environmentally benign and less expensive than alkyl halides.M oreover,a lkylations with alcohols form water as the only by-product. Over the last decade,a lkylations with primary alcohols using the "borrowing hydrogen" methodology have emerged as powerful and green processes for C À Ca nd C À Nb ond formations.[3] Well-developed reactions include N-alkylations of amines and sulfonamides, [3g,4] balkylations of alcohols (Guerbet reactions), [5] a-alkylation of ketones, [6] etc.[7]The a-alkylation of unactivated ester with primary alcohols,however, has remained achallenging and significant goal. Recently,the group of Ishii reported the only examples of a-alkylation of unactivated ester with alcohols.[8] The reactions occurred at 100 8 8CintBuOH with acombination of 5mol %[ {Ir(cod)Cl} 2 ]a nd 15 mol %P Ph 3 in the precense of 2equivalents of KOtBu. Thework represents abreakthrough in catalytic ester alkylations,but is restricted to reactions with tert-butyl acetate,a nd al arge excess of this ester (10 equiv relative to alcohol) was required.[8] tert-Butyl acetate is relatively easy for alkylation compared to other acetates containing smaller substituents.[1a] To the best of our knowledge,however,nocatalyst systems have been reported for aalkylations of unactivated esters other than that of tert-butyl acetate with a...

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Section: Methodsmentioning

confidence: 99%

A General and Mild Catalytic α‐Alkylation of Unactivated Esters Using Alcohols

Guo

Fang

et al. 2015

Angewandte Chemie

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“…In the synthesis of the hypocholesterolemic agent 1233A, 34 cycloadduct 96, obtained in 58% yield and as a single stereoisomer, was submitted in reduction, protection, and Heck reactions before hydrolysis of the chiral auxiliary (Scheme 22). 35 Similarly, in the synthesis of the hemisynthetic pancreatic lipase inhibitor tetrahydrolipstatin, 36 carbon chain homologation of cycloadduct 100 through diisobutylaluminum hydride reduction, oxidation, and Wittig reaction occurred without any side reactions. 37 In both cases, the mild conditions for reduction of the chiral auxiliary allowed the preparation of highly functionalized oxygenated compounds.…”

Section: Scheme 20mentioning

confidence: 99%

Camphor Derivatives in Asymmetric Cycloadditions and Rearrangements

Langlois¹,

Kouklovsky²

2009

Synlett

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C a m p h o r D e r i v a t i v e s i n A s y m m e t r i c C y c l o a d d i t i o n s a n d R e a r r a n g e m e n t s Abstract: Camphor-derived a,b-unsaturated oxazolines and oxazoline N-oxides are, respectively, useful dienophiles and dipolarophiles in [2+4] and [2+3] diastereoselective cycloadditions. The scope and limitations of these two reactions as well as their synthetic applications in the synthesis of various natural products are discussed. The Account also covers s-[2,3] rearrangement of oxazoline N-oxide, which gives a new insight into the mechanism of this type of reaction. Finally, recent developments in Diels-Alder organocatalyzed cycloaddition with camphor-derived sulfonylhydrazines are also discussed.

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“…Ghosh et al [26] synthesized ( + )-cryptophycin 52, a potent antimitotic antitumor agent, by using chiral 4-phenyl-γ -butyrolactone as a building block. This γ -lactone was also used for the preparation of other biologically active compounds [27,28] . In addition, Kotkar et al [29] reported the synthesis of ( + )-harzialactone starting with chiral 5-phenyl-γ -pentalactone.…”

Section: Introductionmentioning

confidence: 99%

Preparation of optically active 4-substituted γ-lactones by lipase-catalyzed optical resolution

Shimotori

Hoshi

Inoue

et al. 2015

Heterocyclic Communications

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Optically active 4-substituted γ -lactones ( 3 and 4 ) were synthesized effectively using lipase-catalyzed optical resolution. N -methyl-4-hydroxyalkanamides ( rac -1a -i ) as substrates were prepared from N -methylsuccinimide. The alkylation of N -methylsuccinimide using Grignard reagents generated from various alkyl halides followed by reduction resulted in N -methyl-4-hydroxyalkanamides. The optical resolution of rac -1a -g was performed using Novozym 435-catalyzed stereoselective acetylation. The stereoselective preparation of 4-substituted γ -lactones ( 3 and 4 ) possessing various side chains such as isopentyl, phenyl, and phenethyl groups was achieved with more than 90% enantiopurity.

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Asymmetric Synthesis of anti-Aldol Segments via a Nonaldol Route: Synthetic Applications to Statines and (−)-Tetrahydrolipstatin

Cited by 51 publications

References 91 publications

A General and Mild Catalytic α‐Alkylation of Unactivated Esters Using Alcohols

A General and Mild Catalytic α‐Alkylation of Unactivated Esters Using Alcohols

Camphor Derivatives in Asymmetric Cycloadditions and Rearrangements

Preparation of optically active 4-substituted γ-lactones by lipase-catalyzed optical resolution

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