The 1,4‐diacyloxylation of 1,3‐cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing
We describe convenient preparations of
- Award ID(s):
- 1954745
- PAR ID:
- 10411033
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Helvetica Chimica Acta
- Volume:
- 106
- Issue:
- 5
- ISSN:
- 0018-019X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract cis ‐selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2, which limit process sustainability and large‐scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ withtert ‐butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch fromtrans tocis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports highcis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large‐scale applications. -
more » « less
Abstract The 1,4‐diacyloxylation of 1,3‐cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing
cis ‐selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2, which limit process sustainability and large‐scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ withtert ‐butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch fromtrans tocis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports highcis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large‐scale applications. -
more » « less
Abstract A variety of 1‐aryl‐1,3‐dienes were isomerized from
E toZ isomers by photocatalysis using Ru(bpy)3[PF6]2and blue LED light. Enrichment of theZ ‐isomer is thought to occur by selective triplet energy transfer from the photocatalyst to the stereoisomeric mixture. The 1,3‐diene starting materials are easily made by catalytic ene‐yne metathesis (EYM). To access 1,3‐dieneZ ‐stereoisomers directly, a one pot procedure was developed. Additional 1,3‐dienes were investigated for both isomerization andZ ‐enrichment. The combination of cross EYM with photocatalysis allows for the stereoconvergent synthesis ofZ ‐1,3‐dienes. -
more » « less
Abstract The rotational barrier about the CN carbamate bond of
N ‐(4‐hydroxybutyl)‐N ‐(2,2,2‐trifluoroethyl)tert ‐butyl carbamate1 was determined by variable temperature (VT)13C and19F NMR spectroscopy. The −CH2CF3 appendage reports on rotational isomerism and allows for the observation of separate signals for theE ‐ andZ ‐ensembles at low temperature. The activation barrier forE /Z ‐isomerization was quantified using Eyring‐Polanyi theory which requires the measurements of the maximum difference in Larmor frequency Δν max and the convergence temperatureT c. Both Δν max andT c were interpolated by analyzing sigmoidal functions fitted to data describing signal separation and the quality of the superposition of theE ‐ andZ ‐signals, respectively. Methods for generating the quality‐of‐fit parameters for Lorentzian line shape analysis are discussed. Our best experimental value for the rotational barrier ΔG c≠(1 )=15.65±0.13 kcal/mol is compared to results of a higher level ab initio study of the modelN ‐ethyl‐N ‐(2,2,2‐trifluoroethyl) methyl carbamate. -
The cis – trans isomerization of (thio)amides was studied by DFT calculations to get the model for the higher preference for the cis conformation by guided predictive chemistry, suggesting how to select the alkyl/aryl substituents on the C/N atoms that lead to the trans isomer. Multilinear analysis, together with cross-validation analysis, helped to select the best fitting parameters to achieve the energy barriers of the cis to trans interconversion, as well as the relative stability between both isomers. Double experimental check led to the synthesis of the best trans candidate with sterically demanding t -butyl substituents, confirming the utility of predictive chemistry, bridging organic and computational chemistry.more » « less
