Sulfonation with Inversion by Mitsunobu Reaction:  An Improvement on the Original Conditions

While the use of triphenylphosphine as a reductant is common in organic synthesis, the resulting triphenylphosphine oxide (TPPO) waste can be difficult to separate from the reaction product. While a number of strategies to precipitate TPPO are available, none have been reported to work in more polar solvents. We report here that mixing ZnCl2 with TPPO precipitates a TPPO–Zn complex in high yield in several common polar organic solvents. The solvent compatibility of this procedure and the reliability of the precipitation in the presence of polar functional groups were examined to show the utility and limitations of this method.

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“…13 As another example, chemists at Squibb found that, in toluene, they could remove TPPO and diisopropylurea as a 1:1 complex. 14 …”

Section: Introductionmentioning

confidence: 99%

Removal of Triphenylphosphine Oxide by Precipitation with Zinc Chloride in Polar Solvents

2017

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“…Notably, the aryloxy substituents have opposite conformational preferences from the sulfur (thioether) analogues: the 4 S -phenyl thioether prefers an exo ring pucker and compact ϕ , ψ (CSD: TUHMUE, of the angiotensin-converting enzyme inhibitor drug zofenopril), due to the balance of steric over stereoelectronic effects for the larger and less electronegative sulfur atom. 7e, 34 …”

Section: Discussionmentioning

confidence: 99%

4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S-propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions

et al. 2016

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Bioorthogonal reactions allow the introduction of new functionalities into peptides, proteins, and other biological molecules. The most readily accessible amino acids for biooorthogonal reactions have modest conformational preferences or bases for molecular interactions. Herein we describe the synthesis of 4 novel amino acids containing functional groups for bioorthogonal reactions. (2S,4R)- and (2S,4S)-iodophenyl ethers of hydroxyproline are capable of modification via rapid, specific Suzuki and Sonogashira reactions in water. The synthesis of these amino acids, as Boc-, Fmoc- and free amino acids, was achieved through succinct sequences. These amino acids exhibit well-defined conformational preferences, with the 4S-iodophenyl hydroxyproline crystallographically exhibiting β-turn (ϕ, ψ ~ −80°, 0°) or relatively extended (ϕ, ψ ~ −80°, +170°) conformations, while the 4R- diastereomer prefers a more compact conformation (ϕ ~ −60°). The aryloxyproline diastereomers present the aryl groups in a highly divergent manner, suggesting their stereospecific use in molecular design, medicinal chemistry, and catalysis. Thus, the 4R- and 4S-iodophenyl hydroxyprolines can be differentially applied in distinct structural contexts. The pentynoate ester of 4R-hydroxyproline introduces an alkyne functional group within an amino acid that prefers compact conformations. The propargyl thioether of 4-thiolphenylalanine was synthesized via copper-mediated cross-coupling reaction of thioacetic acid with protected 4-iodophenylalanine, followed by thiolysis and alkylation. This amino acid combines an alkyne functional group with an aromatic amino acid and the ability to tune aromatic and side chain properties via sulfur oxidation. These amino acids provide novel loci for peptide functionalization, with greater control of conformation possible than with other amino acids containing these functional groups.

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“…For the Mitsunobu reaction, see: Mitsunobu (1981); Hughes (1992), Swamy et al (2009). For the structures of analogous compounds, see: Anderson et al (1996); Hé roux & Brisse (1997); Wang et al (2007). For the synthesis of this and related compounds, see Doboszewski (1997Doboszewski ( , 2009.…”

Section: Related Literaturementioning

confidence: 99%

“…Even though the Mitsunobu reaction has been known for over 40 years, only in 1996 has an X-ray structure of a similar complex (Anderson et al, 1996, Héroux & Brisse, 1997 been published and its stability was attributed to strong association via hydrogen bonding. The present communication shows a second compound of this kind.…”

Section: S1 Commentmentioning

confidence: 99%

Dimethyl hydrazine-1,2-dicarboxylate–triphenylphosphine oxide (1/1)

et al. 2011

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Key indicators: single-crystal X-ray study; T = 200 K; mean (C-C) = 0.003 Å; R factor = 0.036; wR factor = 0.095; data-to-parameter ratio = 13.0.In the crystal structure of the title compound, C 4 H 8 N 2 O 4 Á-C 18 H 15 OP, two triphenylphosphine oxide molecules and two dimethyl hydrazine-1,2-dicarboxylate molecules are connected via N-HÁ Á ÁO hydrogen bonds of moderate strength and are related via a twofold rotational axis. Weak C ar -HÁ Á Á O contacts strengthen the crystal structure. Related literature ExperimentalCrystal data

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Sulfonation with Inversion by Mitsunobu Reaction: An Improvement on the Original Conditions

Cited by 62 publications

References 33 publications

Removal of Triphenylphosphine Oxide by Precipitation with Zinc Chloride in Polar Solvents

Removal of Triphenylphosphine Oxide by Precipitation with Zinc Chloride in Polar Solvents

4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S-propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions

Dimethyl hydrazine-1,2-dicarboxylate–triphenylphosphine oxide (1/1)

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