- Palladium/PC-Phos-Catalyzed Enantioselective Arylation of General Sulfenate Anions: Scope and Synthetic Applications
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Herein we reported an efficient palladium-catalyzed enantioselective arylation of both alkyl and aryl sulfenate anions to deliver various chiral sulfoxides in good yields (up to 98%) with excellent enantioselectivities (up to 99% ee) by the use of our developed chiral O,P-ligands (PC-Phos). PC-Phos are easily prepared in short steps from inexpensive commercially available starting materials. The single-crystal structure of the PC4/PdCl2 showed that a rarely observed 11-membered ring was formed via the O,P-coordination with the palladium(II) center. The salient features of this method include general substrate scope, ease of scale-up, applicable to the late-stage modification of bioactive compounds, and the synthesis of a marketed medicine Sulindac.
- Wang, Lei,Chen, Mingjie,Zhang, Peichao,Li, Wenbo,Zhang, Junliang
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p. 3467 - 3473
(2018/03/13)
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- Investigation of functionalized α-chloroalkyllithiums for a stereospecific reagent-controlled homologation approach to the analgesic alkaloid (-)-epibatidine
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Four putative functionalized α-chloroakyllithiums RCH 2CHLiCl, where R=CHCH2 (18 a), CCH (18 b), CH 2OBn (18 c), and CH[O(CH2)2O] (18 d), were generated in situ by sulfoxide-lithium exchange from α-chlorosulfoxides, and investigated for the stereospecific reagent-controlled homologation (StReCH) of phenethyl and 2-chloropyrid-5-yl (17) pinacol boronic esters. Deuterium labeling experiments revealed that α-chloroalkyllithiums are quenched by proton transfer from their α-chlorosulfoxide precursors and it was established that this effect compromises the yield of StReCH reactions. Use of α-deuterated α-chlorosulfoxides was discovered to ameliorate the problem by retarding the rate of acid-base chemistry between the carbenoid and its precursor. Carbenoids 18 a and 18 b showed poor StReCH efficacy, particularly the propargyl group bearing carbenoid 18 b, the instability of which was attributed to a facile 1,2-hydride shift. By contrast, 18 d, a carbenoid that benefits from a stabilizing interaction between O and Li atoms gave good StReCH yields. Boronate 17 was chain extended by carbenoids 18 a, 18 b, and 18 d in 16, 0, and 68 % yield, respectively; α-deuterated isotopomers D-18 a and D-18 d gave yields of 33 and 79 % for the same reaction. Double StReCH of 17 was pursued to target contiguous stereodiads appropriate for the total synthesis of (-)-epibatidine (15). One-pot double StReCH of boronate 17 by two exposures to (S)-D-18 a (≤66 % ee), followed by work-up with KOOH, gave the expected stereodiad product in 16 % yield (d.r.~67:33). The comparable reaction using two exposures to (S)-D-18 d (≤90 % ee) delivered the expected bisacetal containing stereodiad (R,R)-DD-48 in 40 % yield (≥98 % ee, d.r.=85:15). Double StReCH of 17 using (S)-D-18 d (≤90 % ee) followed by (R)-D-18 d (≤90 % ee) likewise gave (R,S)-DD-48 in 49 % yield (≥97 % ee, d.r.=79:21). (R,S)-DD-48 was converted to a dideuterated isotopomer of a synthetic intermediate in Corey's synthesis of 15. Copyright
- Emerson, Christopher R.,Zakharov, Lev N.,Blakemore, Paul R.
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p. 16342 - 16356
(2013/12/04)
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- Investigation of steric and electronic effects in the copper-catalysed asymmetric oxidation of sulfides
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Steric and electronic effects in the copper-catalysed asymmetric oxidation of aryl benzyl, aryl alkyl and alkyl benzyl sulfides have been investigated. The presence of an aryl group directly attached to the sulfur is essential to afford sulfoxides with high enantioselectivities, with up to 97% ee for 2-naphthyl benzyl sulfoxide, the highest enantioselectivity achieved to date for copper-catalysed asymmetric sulfoxidation. In contrast, the benzyl substituent can be replaced by sterically comparable groups with no effect on enantioselectivity. Copper-mediated oxidation of substituted aryl benzyl sulfides display modest steric and electronic effects resulting in comparable or lower enantioselectivities to those obtained with the unsubstituted benzyl phenyl sulfide.
- O'Mahony, Graham E.,Eccles, Kevin S.,Morrison, Robin E.,Ford, Alan,Lawrence, Simon E.,Maguire, Anita R.
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p. 10168 - 10184
(2013/11/06)
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- Iterative stereospecific reagent-controlled homologation using a functionalized α-chloroalkyllithium: Synthesis of cyclic targets related to epibatidine
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Enantioenriched 1-chloro-2-(1,3-dioxolan-2-yl)ethyllithium was generated by PhLi initiated sulfoxide-ligand exchange and deployed in situ for sequential double stereospecific reagent-controlled homologation (StReCH) of B-(2-chloro-pyrid-5-yl) pinacol boronate. This process afforded highly functionalized contiguous stereodiad motifs (typically, % ee ≥ 98%, dr ≥ 85:15) amenable to subsequent annulative transformations as demonstrated by the concise synthesis (5-7 steps) of cyclic adducts related to the analgesic alkaloid epibatidine.
- Emerson, Christopher R.,Zakharov, Lev N.,Blakemore, Paul R.
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p. 1318 - 1321
(2011/04/26)
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- Practical and highly stereoselective technology for preparation of enantiopure sulfoxides and sulfinamides utilizing activated and functionally differentiated N-sulfonyl-1,2,3-oxathiazolidine-2-oxide derivatives
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A simple, general, and practical technology to prepare enantiopure 1,2,3-oxathiazolidine-2-oxide derivatives using chiral aryl N-sulfonyl aminoalcohol derivatives and thionyl chloride is reported. The versatility of these novel chiral building blocks (MIOO and TMPOO), was exemplified by the expedient production of a variety of unique chiral sulfoxides and valuable chiral sulfinamides in excellent yields and enantiopurities.
- Han, Zhengxu,Krishnamurthy, Dhileepkumar,Grover, Paul,Fang, Q. Kevin,Su, Xiping,Wilkinson, H. Scott,Lu, Zhi-Hui,Magiera, Daniel,Senanayake, Chris H.
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p. 6386 - 6408
(2007/10/03)
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- Stereochemical studies of the palladium-catalyzed rearrangements of chiral 2-alkynyl sulfinates into chiral allenyl sulfones
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Palladium-catalyzed reactions of diastereomerically pure chiral 2-alkynyl p-toluenesulfinates under very mild reaction conditions gave both enantiomers of optically active sulfonyl allenes in good yields with high stereospecificity. The stereochemistry of this transformation with the assistance of a palladium catalyst was determined. The conversion rate was measured by the HPLC analysis in accordance with the elapse of the reaction time, and the rather marked difference of the rate was observed between the diastereomeric sulfinates. A novel mechanism for this transformation with palladium catalysts is proposed.
- Hiroi, Kunio,Kato, Fumiko
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p. 1543 - 1550
(2007/10/03)
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- Extremely Facile Ligand-Exchange and Disproportionation Reactions of Diaryl Sulfoxides, Selenoxides, and Triarylphosphine Oxides with Organolithium and Grignard Reagents
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Diaryl sulfoxides undergo unusually rapid ligand-exchange reaction upon treatment with organolithium reagents at -95 deg C.Optically pure phenyl p-tolyl sulfoxide (4b) reacted with organolithium reagents at the range from -20 to -95 deg C to give facile ligand-exchange and disproportionation products, i.e., diphenyl sulfoxide (7), recovered 4b, and di-p-tolyl sulfoxide (8) in a statistical ratio of 1:2:1 in quantitative yields, and the recovered 4b was completely racemized.This facile ligand exchange was observed in the similar reactions using only diaryl selenoxides and triarylphosphine oxides.The reactions of 18O-labeled phenyl p-tolyl sulfoxide (4c) with organolithium reagents gave products in a statistical ration without 18O scrambling, indicating that only the C-S bond cleavage took place under low temperature.It is suggested that the ligand exchange reactions occur by the nucleophilic attack by organolithium reagent at the sulfinyl sulfur atom, giving ?-sulfurane as an intermediate that collapses rapidly.These results suggest that the treatment of arylic sulfoxides, selenoxides, and phosphine oxides with strong bases should be effected with caution.
- Furukawa, Naomichi,Ogawa, Satoshi,Matsumura, Kazunori,Fujihara, Hisashi
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p. 6341 - 6348
(2007/10/02)
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- Studies on Chiral Organo-Sulfur Compounds. II. Stereochemistry of Thermal Chiral Allyl Sulfinate-Sulfone Rearrangements
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A highly efficient and general synthetic route to optically active sulfinates by the stereospecific boron trifluoride etherate-catalyzed esterification of sulfinamides was developed.Dramatic solvent effects were observed in the thermal transformation of allyl sulfinate derivatives to sulfones.Heating of chiral trans- and cis-allyl sulfinates, (S)-(-)-3a,c,e and (S)-(-)-3b,d,f, in N,N-dimethylformamide at 90-120 deg C provided chiral sulfones (S)-(+)- and (R)-(-)-5,6,7 in good yields, respectively, with exceedingly high stereospecificity. Keywords - asymmetric transfer; stereospecificity; chiral allyl sulfinate; chiral allyl sulfone; boron trifluoride etherate; thermolysis
- Hiroi, Kunio,Kitayama, Ryuichi,Sato, Shuko
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p. 2628 - 2638
(2007/10/02)
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