Catalytic Asymmetric Synthesis of Tertiary Alcohols and Oxetenes Bearing a Difluoromethyl Group

Aikawa, Kohsuke; Yoshida, Seiya; Kondo, Daisuke; Asai, Yuya; Mikami, Kōichi

doi:10.1021/acs.orglett.5b02617

Cited by 36 publications

(16 citation statements)

References 67 publications

(18 reference statements)

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“…To date, elaboration of prochiral electrophiles bearing pre-installed CHF 2 groups has been the most widely studied strategy for generating enantioenriched CHF 2 -containing small molecules (Fig. 1B) (10, 11, 12, 13). Deoxyfluorination of aldehydes (14, 15, 16) is a conceptually straightforward approach to constructing CHF 2 groups, but α-branched chiral aldehydes are prone to epimerization and other decomposition pathways (15, 17, 18), whereas α-quaternary aldehydes are susceptible to rearrangement reactions (14, 19, 20, 21) (Fig.…”

mentioning

confidence: 99%

Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters

Banik

Medley

Jacobsen

2016

Science

286

134

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Difluoromethyl groups possess specific steric and electronic properties that invite their use as chemically inert surrogates of alcohols, thiols, and other polar functional groups important in a wide assortment of molecular recognition processes. We report here a method for the catalytic, asymmetric, migratory geminal difluorination of β-substituted styrenes to access a variety of products bearing difluoromethylated tertiary or quaternary stereocenters. The reaction uses commercially available reagents (mCPBA and HF•pyridine) and a simple chiral aryl iodide catalyst, and is carried out readily on gram scale. Substituent effects and temperature-dependent variations in enantioselectivity suggest that cation-π interactions play an important role in stereodifferentiation by the catalyst.

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mentioning

confidence: 99%

Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters

Banik

Medley

Jacobsen

2016

Science

286

134

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“…Later on, Mikami group further extended this catalyst system [( S )‐ 103 /Pd(SbF 6 ) 2 ] to the ene reactions of difluoropyruvate with alkenes (Scheme ) . Mono‐, 1,1‐di‐, and trisubstituted alkenes were all compatible to afford the ene‐products, α ‐CF 2 H tertiary alcohols 105 in up to 99% yield, 99% ee .…”

Section: Ketone‐(hetero)ene Reactionsmentioning

confidence: 99%

Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

2018

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Chiral tertiary alcohols are an important class of organic compounds which have found wide applications in both academia and industry. Therefore, various synthetic strategies towards these compounds have already been developed. Among them, the catalytic asymmetric addition of carbon nucleophiles to ketones is the most desirable route owing to its straightforwardness as well as its economic, efficient and versatile advantages. This review summarizes and discusses the recent achievements in this field classified according to the reaction types. Special attention is paid to the mechanisms, advantages and limitations of each reaction. In addition, the applications of these catalytic processes in the synthesis of related natural products, pharmaceuticals or their analogues are briefly discussed as well.

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“…13 C NMR (101 MHz, THF-d8) δ (ppm) 161.0 (t, J = 27.0 Hz), 139. 6,137.0,130.1,128.5,119.2 (t,J = 302.5 Hz). IR ν (cm -1 ) 3096, 2919,2851,2646,2508,1768,1572,1478,1426,1395,1275,1175,1139,1114,1079,1035,1010,947,887,827,772,745,702.…”

Section: -[(4-chlorophenyl)sulfinyl]-22-difluoroacetic Acid 17bmentioning

confidence: 99%

“…4 This is for instance the case for the synthesis of highly enantioenriched α-difluoromethyl alcohols. They can be accessed through bio-and organometallic reductions of α,α-difluoro ketones, 5 pallado-catalyzed reductive coupling 6 or enantioselective difluoromethylations involving naked CHF2anion surrogates in presence of different chiral quaternary ---* Corresponding authors. e-mail addresses: frederic.leroux@unistra.fr, ghanquet@unistra.fr.…”

Section: Introductionmentioning

confidence: 99%

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

et al. 2019

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The-CHF2 moiety has shown a growing interest in pharmaceutical and agrochemical applications over the last few years. Its introduction is therefore a current research topic for organic chemists. Several groups have reported the synthesis of difluoromethylated compounds. However, the more challenging enantioselective introduction of the difluoromethyl group has been scarcely described yet. We recently developed a new strategy, based on the use of an enantiopure difluoromethyl sulfoxide used as chiral and traceless auxiliary, for the synthesis of highly enantioenriched αdifluoromethyl alcohols. 8 The first method developed in our laboratory aims to access highly stereoenriched α,α-difluoro-β-hydroxysulfoxides through the condensation of the enantiopure difluoromethyl sulfoxide on carbonyl derivatives. It is noteworthy that highly diastereo-and enantioenriched α,α-difluoro-β-hydroxysulfoxides can also be accessed after the diastereoselective reduction of highly enantioenriched α,α-difluoro-β-ketosulfoxides. Finally, the expected difluoromethyl-substituted alcohols can be obtained after removal of the chiral auxiliary with complete retention of stereoenrichment at carbon.

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Catalytic Asymmetric Synthesis of Tertiary Alcohols and Oxetenes Bearing a Difluoromethyl Group

Cited by 36 publications

References 67 publications

Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters

Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters

Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

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