Enantiomerically Pure Tertiary Alcohols by TADDOL-Assisted Additions to Ketones—or How to Make a Grignard Reagent Enantioselective

1992 ◽  
Vol 31 (1) ◽  
pp. 84-86 ◽  
Author(s):  
Beat Weber ◽  
Dieter Seebach
Keyword(s):  
Grignard Reagent ◽  
Enantiomerically Pure ◽  
Tertiary Alcohols

Alkene Metathesis: Synthesis of Panaxytriol (Lee), Isofagomine (Imahori and Takahata), Elatol (Stoltz), 5-F2t -Isoprostane (Snapper), and Ottelione B (Clive)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Grignard Reagent ◽  
Conjugate Addition ◽  
Ring Closing Metathesis ◽  
University Of Illinois ◽  
Enantiomerically Pure ◽  
University Of Alberta ◽  
Cross Metathesis ◽  
Grubbs Catalysts ◽  
The University ◽  
First And Second Generation

Alkene metathesis has been used to prepare more and more challenging natural products. The first and second generation Grubbs catalysts 1 and 2 and the Hoveyda catalyst 3 are the most widely used. Daesung Lee of the University of Illinois at Chicago designed (Organic Lett. 2008, 10, 257) a clever chain-walking cross metathesis, combining 4 and 5 to make 6. The diyne 3 was carried on (3R, 9R, 10R )-Panaxytriol 7. Tatsushi Imahori and Hiroki Takahata of Tohoku Pharmaceutical University found (Tetrahedron Lett. 2008, 49, 265) that of the several derivatives investigated, the unprotected alcohol 8 cyclized most efficiently. Selective cleavage of the monosubstituted alkene followed by hydroboration delivered the alkaloid Isofagomine 10. Brian M. Stoltz of Caltech established (J. Am. Chem. Soc. 2008 , 130 , 810) the absolute configuration of the halogenated chamigrene Elatol 14 using the enantioselective enolate allylation that he had previously devised. A key feature of this synthesis was the stereocontrolled preparation of the cis bromohydrin. Marc L. Snapper of Boston College opened (J. Org. Chem. 2008, 73, 3754) the strained cyclobutene 15 with ethylene to give the diene 16. Remarkably, cross metathesis with 17 delivered 18 with high regioselectivity, setting the stage for the preparation of the 5-F2t - Isoprostane 19. Derrick L. J. Clive of the University of Alberta assembled (J. Org. Chem. 2008, 73, 3078) Ottelione B 26 from the enantiomerically-pure aldehyde 20. Conjugate addition of the Grignard reagent 21 derived from chloroprene gave the kinetic product 22, that was equilibrated to the more stable 23. Addition of vinyl Grignard followed by selective ring-closing metathesis then led to 26.

scholarly journals Modern Friedel-Crafts chemistry: Part 36. Facile synthesis of some new pyrido[3,2,1-jk]carbazoles via Friedel-Crafts cyclialkylations

2013 ◽  
Vol 78 (5) ◽  
pp. 611-619 ◽  
Author(s):  
Abd El-Aal ◽  
Ali Khalaf
Keyword(s):  
Grignard Reagent ◽  
Grignard Reagents ◽  
Facile Synthesis ◽  
Tertiary Alcohols

An efficient methodology for the synthesis of novel substituted pyrido[3,2,1-jk]carbazole via Friedel-Crafts cyclialkylations is reported. The methodology was realized by three-step protocol involved the addition of carbazole to 3-methylcrotononitrile. The resulted nitrile was hydrolyzed to desired ester, followed by addition of Grignard reagents to afford tertiary alcohols and/or reacted directly with different Grignard reagent to form the desired ketones. The later ketones were converted to both secondary and tertiary alcohols by reduction with LAH and addition of Grignard reagents respectively. These carbinols were cyclialkylated under Friedel-Crafts conditions catalyzed by AlCl3/CH3NO2, PTSA and PPA to give tri-and tetrasubstituted pyrido[3,2,1-jk]carbazole.

Diversity-oriented synthesis of enantiopure N-protected β,β-dialkylserines

2004 ◽  
Vol 82 (2) ◽  
pp. 318-324 ◽  
Author(s):  
James E Dettwiler ◽  
William D Lubell
Keyword(s):  
Amino Acid ◽  
Methyl Ester ◽  
Grignard Reagent ◽  
Primary Alcohol ◽  
Sodium Chlorite ◽  
Ring Closing Metathesis ◽  
Diversity Oriented Synthesis ◽  
Enantiomerically Pure ◽  
Catalysed Oxidation

A series of enantiomerically pure N-Boc-protected β,β-dialkylserines was synthesized by addition of the appropriate Grignard reagent to N-(Boc)serine methyl ester, followed by TEMPO-catalysed oxidation of the primary alcohol with sodium chlorite and sodium hypochlorite.Key words: amino acid, serine, β,β-dialkylserines, ring-closing metathesis.

The Lee Synthesis of (−)-Crinipellin A

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Grignard Reagent ◽  
Conjugate Addition ◽  
Dipolar Cycloaddition ◽  
University Of Delaware ◽  
Initial Formation ◽  
Enantiomerically Pure ◽  
Silyl Enol Ether ◽  
Single Diastereomer ◽  
Sharpless Asymmetric Epoxidation ◽  
The University

The crinipellins are the only tetraquinane natural products. The enone crinipellins, including crinipellin A 3, have anticancer activity. Hee-Yoon Lee of the Korea Advanced Institute of Science and Technology (KAIST) envisioned (J. Am. Chem. Soc. 2014, 136, 10274) the assembly of 2 and thus 3 by the intramolecular dipolar cycloaddition of the diazoalkane derived from the tosylhydrazone 1. The initial cyclopentene was prepared from commercial 4 following the Williams procedure. Conjugate addition of the Grignard reagent 5 in the presence of TMS-Cl led to the silyl enol ether 6. Regeneration of the enolate followed by allylation gave 7. The preparation of the racemic ketone was completed by ozonolysis followed by selec­tive reduction and protection. Addition of hydride in an absolute sense led to separa­ble 1:1 mixture of diastereomers. Reoxidation of one of the diastereomers delivered enantiomerically enriched 8. A few steps later, after coupling with 10, the sidechain stereocenter was set by Sharpless asymmetric epoxidation. Oxidation of 11 gave the aldehyde, that was converted to the alkyne 12 by the Ohira protocol. Addition of the Grignard reagent 13 gave the allene 14 as an inconse­quential 1:1 mixture of diastereomers. Deprotection then led to the tosylhydrazone 1. The transformation of 1 to 2 proceeded by initial formation of the diazo alkane 15. Intramolecular dipolar cycloaddition gave 16, that lost N2 to give the trimethylene–methane diradical 17. The insertion into the distal alkene proceeded with remarkable stereocontrol, to give 2 as a single diastereomer—in 87% yield from 1. Direct α-hydroxylation of the ketone derived from 2 gave the wrong diastereo­mer, and hydride addition to 18 reduced the wrong ketone. As an alternative, the enantiomerically-pure sulfoximine anion was added to the more reactive ketone, and the product was reduced and protected to give 19. Allylic oxidation converted the alkene to the enone, and heating to reflux in toluene reversed the sulfoximine addi­tion, leading to 20. Epoxidation of 20 followed by α-methylenation delivered the enone 21, that proved to be particularly sensitive. Eventually, success was found with TASF. With a similarly sensitive substrate, Douglass F. Taber of the University of Delaware observed (J. Am. Chem. Soc. 1998, 120, 13285) that TBAF in THF buffered with solid NH4Cl worked well.

Diphenyl-5,6,7,7a-tetrahydropyrrolo[1,2-c]oxazol-3(1H)-one

2007 ◽  
Vol 63 (3) ◽  
pp. o1108-o1109
Author(s):  
Bing-Tao Wang ◽  
Hua-Dong Yue ◽  
Shu-Ping Luo ◽  
Li-Ping Wang ◽  
Dan-Qian Xu
Keyword(s):  
Title Compound ◽  
Grignard Reagent ◽  
Chair Conformation ◽  
Asymmetric Unit ◽  
Enantiomerically Pure ◽  
Compound C

The title compound, C18H17NO2, synthesized from enantiomerically pure L-proline, methyl chloroformate and a Grignard reagent, crystallizes with two molecules in the asymmetric unit. A chair conformation is adopted by the two fused five-membered rings.

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