Synthesis of new chiral sulfinyldiacetic acid derivatives and attempt at chemoselective asymmetric Pummerer reaction

(R(S))-1 (85% ee) was prepared by utilizing a porcin pancreatic lipase-promoted hydrolysis of sulfinyldiacetic acid dimethyl ester (8) which was derived from thiodiacetic acid (7). (R(S))-1 (99% ee) and (S(S))-1 (99% ee) were readily obtained by methanolysis of (R(S),S)-12 and (S(S),S)-12 with MeONa in MeOH. (R(S),S)-12 and (S(S),S)-12 were furnished by chromatographic separation of the diastereomeric mixture, obtained by oxidation of thiodiacetic mono-carboxylic acid (11) with 30% H2O2 followed by dehydrative condensation of the resultant sulfinyldiacetic mono-carboxylic acid with 4(S)-isopropyl-1,3-thiazolidine-2-thione. (R(S))-1 (99% ee) was successively treated with (TMS)2NLi, Ac2O, and TMSOTf to give a major chiral-3 product in 75% ee and in a highly chemoselective manner (chiral-3:chiral-2=93:7).     

Diastereomer method for determining ee by (1)H NMR and/or MS spectrometry with complete removal of the kinetic resolution effect

[structure: see text] Using chiral auxiliaries, 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid) (S)-(+)-1 and its deuterium-labeled enantiomer (R)-(-)-1-d(n)() (n = 3 or 6), we have developed a new diastereomer method for determining enantiomeric excess (% ee) of chiral alcohols by (1)H NMR and/or MS spectrometry, where the kinetic resolution effect is completely excluded. The data of % ee determined by this method agree well with those calculated by weight, the average error being ca. +/-1.08% ee.     

(5R,6R)-6-苯基-5-(苯磺酰基乙酰基)二环[2.2.1]-2-庚烯的合成及结构表征

报道了一种制备4-苯基-1-苯磺酰基-3-丁烯-2-酮的新合成方法. 4-苯基-3-丁烯-2-酮与溴化试剂Ph₃P^＋CH₂CH₂- COOHBr 作用, 得到1-溴-4-苯基-3-丁烯-2-酮, 不经分离直接与苯亚磺酸钠发生亲核取代反应, 得到4-苯基-1-苯磺酰基-3-丁烯-2-酮. 将此反应产物作为亲双烯体与环戊二烯在手性钛金属催化剂催化下进行不对称Diels-Alder反应, 得到了＞99% ee 的环加成产物(5R,6R)-6-苯基-5-(苯磺酰基乙酰基)二环[2.2.1]-2-庚烯. 用X衍射法对产物的晶体结构进行了测定, 讨论了反应机理, 通过元素分析, NMR, MS对产物的结构进行了表征.     

Chiral pyridylamino-ruthenium(II) complexes: synthesis, structure and catalytic properties in Diels-Alder reactions

Half-sandwich complexes [(eta(6)-arene)RuCl(pyam)][SbF(6)] (pyam = L(n) = N-(2-pyridylmethyl)-(R)-1-phenylethylamine (L(1)), N-(2-pyridylmethyl)-(R)-1-naphthylethylamine (L(2)), N-(2-quinolylmethyl)-(R)-1-naphthylethylamine (L(3)), N-(2-pyridylmethyl)-(R)-1-cyclohexylethylamine (L(4)), N-(2-pyridylmethyl)-(1R,2S,4R)-1-bornylamine (L(5))) have been synthetised and characterised. Treatment of these compounds with AgSbF(6) generates dicationic complexes [(eta(6)-arene)Ru(pyam)(H(2)O)](2+) which act as enantioselective catalysts for the Diels-Alder reactions of methacrolein and cyclopentadiene. The catalytic reactions occur quickly at room temperature with good exo : endo selectivity (from 84 : 16 to 98 : 2) and moderate enantioselectivity (up to 74% ee). The molecular structures of the chloride complexes (R(Ru),S(N),R(C))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(1)][SbF(6)], (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(5)][SbF(6)], and that of the aqua complex (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuL(5)(H(2)O)][SbF(6)](2), were determined by X-ray diffractometric methods. The distinctive variations observed in the molecular structures of these complexes only concern the puckering parameters of the metallacycle and the relative disposition of substituents within this ring. A clear trend to localise the most steric demanding substituents at equatorial positions is evident from the structural study.     

New chiral ruthenium(II) catalysts containing 2,6-bis(4'-(R)-phenyloxazolin-2'-yl)pyridine (Ph-pybox) ligands for highly enantioselective transfer hydrogenation of ketones

Treatment of complex trans-[RuCl(2)(eta(2)-C(2)H(4))[kappa(3)-N,N,N-(R,R)-Ph-pybox]] [(R,R)-Ph-pybox = 2,6-bis[4'-(R)-phenyloxazolin-2'-yl]pyridine] with phosphines or phosphites in dichloromethane at 50 degrees C leads to the formation of novel ruthenium(II)-pybox complexes trans-[RuCl(2)(L)[kappa(3)-N,N,N-(R,R)-Ph-pybox]] [L = PPh(3) (1 a), PPh(2)Me (2 a), PPh(2)(C(3)H(5)) (3 a), PPh(2)(C(4)H(7)) (4 a), PMe(3) (5 a), PiPr(3) (6 a), P(OMe)(3) (7 a) and P(OPh)(3) (8 a)]. Likewise, reaction of trans-[RuCl(2)(eta(2)-C(2)H(4))[kappa(3)-N,N,N-(R,R)-Ph-pybox]] with PPh(3) or PiPr(3) in refluxing methanol leads to the complexes cis-[RuCl(2)(L)(kappa(3)-N,N,N-(R,R)-Ph-pybox] [L = PPh(3) (1 b), PiPr(3) (6 b)]. No trans-cis isomerisation of complexes 1 a-8 a has been observed. Complexes 1 a-8 a, 1 b, 6 b together with the analogous trans-[RuCl(2)[P(OMe)(3)][kappa(3)-N,N,N-(S,S)-iPr-pybox]] (10 a) and the previously reported trans- and cis-[RuCl(2)(PPh(3))[kappa(3)-N,N,N-(S,S)-iPr-pybox]] (9 a and 9 b, respectively) are active catalysts for the transfer hydrogenation of acetophenone in 2-propanol in the presence of NaOH (ketone/cat/NaOH 500:1:6). cis-Ph-pybox derivatives are the most active catalysts. In particular, cis complexes 1 b and 6 b led to almost quantitative conversions in less than 5 min with a high enantioselectivity (up to 95 %). A variety of aromatic ketones have also been reduced to the corresponding secondary alcohols with very high TOF and ee up to 94 %. The overall catalytic performance seems to be a subtle combination of the steric and/or electronic properties both the phosphines and the ketones. A high TOF (27 300 h(-1)) and excellent ee (94 %) have been found for the reduction of 3-bromoacetophenone with catalyst 6 b. Reductions of alkyl ketones also proceed with high and rapid conversions but low enantioselectivities are achieved.     

Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: asymmetric synthesis of allylic sulfides,allylic sulfones,and allylic alcohols

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1 a-c and racemic acyclic allylic carbonates rac-3 aa and rac-3 ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate 1 a (>/=99 % ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2 aa, 2 b, 2 c, 2 d and 4 a-c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5 aa, 5 b, 5 ab, 6 aa-ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6 aa, 6 ab, 6 ac and 6 bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1 da and rac-1 db with 2-pyrimidinethiol gave the allylic sulfide 5 c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1 a and of the acyclic carbonates rac-3 aa and rac-3 ba with 2-pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1 a as well as of the highly enriched enantiomers 1 a (>/=99 % ee) and ent-1 a (>/=99 % ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1 a, ent-1 a (>/=99 % ee) and ent-1 c (>/=99 % ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1 a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1 a-c, ent-3 aa and ent-3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9 a-c (>/=99 % ee) and acyclic allylic alcohols 10 a (>/=99 % ee) and 10 b (99 % ee), respectively.     

Asymmetric hydrogenation of aromatic ketones using new chiral-bridged diphosphine/diamine-Ru(Ⅱ) complexes

<正>A series of chiral secondary alcohols were easily prepared by means of asymmetric hydrogenation of prochiral aromatic ketones using a new((R_(ax))-BuP)/(R,R)-DPEN-Ru(Ⅱ) complex catalyst system.The hydrogenation of 2-methylacetophenone in n-butanol (t-BuOK/Ru =45.6/1,S/C = 500,20 atm.of H_2,20℃,48 h) afforded(S)-1-(2'-methylphenyl)ethanol in 92%ee and99% conversion.     

First Resolution of a Free Fluorophosphine Chiral at Phosphorus. Resolution and Reactions of Free and Coordinated (+/-)-Fluorophenylisopropylphosphine

The trivalent fluorophosphine (+/-)-PFPh(i-Pr), (+/-)-1, has been prepared by halogen exchange of the corresponding chlorophosphine with sodium fluoride in hot sulfolane. The neat fluorophosphine rapidly decomposes by equilibrium redox disproportionation into PF(3)Ph(i-Pr) and (R,R)/(R,S)-Ph(i-Pr)PPPh(i-Pr), but in benzene, (+/-)-1 has considerable thermodynamic stability. The resolution of (+/-)-1 was achieved by a fractional crystallization of the diastereomers (R,R(P))- and (R,S(P))-chloro[1-[1-(dimethylamino)ethyl]-2-naphthalenyl-C,N](fluorophenylisopropylphosphine)palladium(II), (R,R(P))- and (R,S(P))-5, whereby the less soluble (R,R(P)) diastereomer selectively crystallized in 64% yield in a typical second-order asymmetric transformation. Optically pure (S)-(-)-1, -210 (c 0.59, C(6)H(6)), was liberated from (R,R(P))-5 with (R,S)-1,2-phenylenebis(methylphenylphosphine). The optically active phosphine in benzene racemizes over 6 h without significant redox disproportionation. The methoxyphosphine (+/-)-P(OMe)Ph(i-Pr), (+/-)-9, was also resolved by the method of metal complexation. Thus, fractional crystallization of (R,R(P))- and (R,S(P))-chloro[1-[1-(dimethylamino)ethyl]-2-naphthalenyl-C,N](methoxyphenylisopropylphosphine)palladium(II), (R,R(P))- and (R,S(P))-8, followed by liberation of the respective optically active methoxyphosphines from the separated diastereomers with 1,2-bis(diphenylphosphino)ethane, gave (R)-(+)- and (S)-(-)-9 of 92% and 96% ee, respectively. The barrier to unimolecular inversion for (+/-)-9 was determined to be >82.9 +/- 0.5 kJ mol(-)(1) by variable temperature (1)H NMR spectroscopy. The substitution of fluoride in (R,R(P))-5 by methoxide proceeds with predominant inversion of the configuration at phosphorus to give (R,R(P))- and (R,S(P))-8 with (R,S(P))/(R,R(P)) = (1)/(5). The crystal structures of (R,R(P))-5 and (R,R(P))-8 have been determined: (R,R(P))-5 (C(23)H(28)ClFNPPd) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 9.967(2) ?, b = 10.998(4) ?, c = 21.324(3) ?, Z = 4, and R = 0.031; (R,R(P))-8 (C(24)H(31)ClNOPPd) crystallizes in the space group P2(1)2(1)2(1) with a = 10.444(3) ?, b = 12.146(3) ?, c = 19.047(2) ?, Z = 4, and R = 0.026.     

替格瑞洛的合成工艺改进

以2-丙硫基-4,6-二氢-5-氨基嘧啶和2-{［(3aR,4S,6R,6aS)-6-氨基-2,2-二甲基四氢-3aH-环戊基［d］［1,3］二氧-4-基］氧}-1-乙醇L-酒石酸盐为原料,经C-N偶联,亲核取代和环合反应制得2-{［(3aR,4S,6R,6aS)-6-(7-氯-5-丙硫基-3H-［1,2,3］三唑［4,5-d］嘧啶-3-基)-2,2-二甲基四氢-3aH-环戊基［d］［1,3］二氧-4-基］氧}-1-乙醇(4); 4与(1R,2S)-2-(3,4-二氟苯基)环丙胺D-扁桃酸盐经亲核取代反应后酸解脱除丙酮叉保护基合成替格瑞洛,总收率58.7%,纯度99.2%,其结构经¹H NMR, MS(ESI)和XRD确证。     

Mechanism of the

Stereochemical studies on [2 + 2] photoaddition of cis-/trans-4-propenylanisole (cis-1 and trans-1) and cis-1-(p-methoxyphenyl)ethylene-2-d(1) (cis-3-d(1)) to C(60) exhibit stereospecificity in favor of the trans-2 cycloadduct in the former case and nonstereoselectivity in the latter. The observed stereoselectivity in favor of the cis-6-d(3) [2 + 2] diastereomer by 12% in the case of the photochemical addition of (E)-1-(p-methoxyphenyl)-2-methyl-prop-1-ene-3,3,3-d(3) (trans-5-d(3)) to C(60) is attributed to a steric kinetic isotope effect (k(H)/k(D) = 0.78). The loss of stereochemistry in the cyclobutane ring excludes a concerted addition and is consistent with a stepwise mechanism. Intermolecular secondary kinetic isotope effects of the [2 + 2] photocycloaddition of 3-d(0) vs 3-d(1), and 3-d(6) as well as 5-d(0) vs 5-d(1), and 5-d(6) to C(60) were also measured. The intermolecular competition due to deuterium substitution of both vinylic hydrogens at the beta-carbon of 3 exhibits a substantial inverse alpha-secondary isotope effect k(H)/k(D) = 0.83 (per deuterium). Substitution with deuterium at both vinylic methyl groups of 5 yields a small inverse k(H)/k(D) = 0. 94. These results are consistent with the formation of an open intermediate in the rate-determining step.     

一种制备盐酸西那卡塞的新方法

（R）-1-萘乙胺与丙烯酰氯发生亲核取代反应制得酰胺（2）; 2与3-三氟甲基碘苯经Heck偶联反应制得α,β-不饱和酰胺（3）; 3经两次还原反应后再与盐酸成盐合成了盐酸西那卡塞,总收率40%,纯度>99.5%, ee值>99.9%,其结构经¹H NMR和¹³C NMR确证。     

Gold(I)-catalyzed intramolecular amination of allylic alcohols with alkylamines

A 1:1 mixture of (1)AuCl [1 = P(t-Bu)(2)o-biphenyl] and AgSbF(6) catalyzes the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. Gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee, 95% de) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield with 96% ee, consistent with the net syn addition of the amine relative to the departing hydroxyl group.     

N-propargylamides via the asymmetric michael addition of B-alkynyl-10-TMS-9- borabicyclo[3.3.2]decanes to N-acylimines

[Structure: see text] The asymmetric synthesis of N-propargylamides through Michael addition of the alkynylborane 1 to N-acylimines is reported. The N-acetylimines provide the best substrates for the process exhibiting high selectivity (56-95% ee) with predictable stereochemistry. In several cases, 5 crystallizes in essentially pure form (97-99% ee) and a single-crystal X-ray structure was also obtained for 5g (R1=R2=Me, R3=o-Cl-C6C4). The process regenerates 4 for its direct conversion back to 1 and facilitates the efficient recovery of the pseudoephedrine.     

Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction: one-pot synthesis of optically active 7-oxabicyclo[2.2.1]heptenes from furfuryl alcohols and beta-substituted acrylic acids

The first lipase-catalyzed domino reaction is described in which the acyl moiety formed during the enzymatic kinetic resolution of furfuryl alcohols (+/-)-3 with a 1-ethoxyvinyl ester 2 was utilized as a part of the constituent structure for the subsequent Diels-Alder reaction. The preparation of ester 2 from carboxylic acid 1 and the subsequent domino reaction were carried out in a one-pot reaction. Therefore, this procedure provides a convenient preparation of the optically active 7-oxabicyclo[2.2.1]heptene derivatives 5, which has five chiral, non-racemic carbon centers, from achiral 1 and racemic 3. The overall efficiency of this process was dependent on the substituent at the C-3 position of 3, and the use of the 3-methylfurfuryl derivatives, (+/-)-3 b and (+/-)-3 f, exclusively produced diastereoselectivity with excellent enantioselectivity to give (2R)-syn-5 (91->/=99 % ee) and (S)-3 (96->/=99 % ee). Similar procedures starting from the 3-bromofurfuryl alcohols (+/-)-3 h-j provided the cycloadducts (2R)-syn-5 j-q (93->/=99 % ee), in which the bromo group was utilized for the installation of bulky substituents to the 7-oxabicycloheptene core.     

Highly enantioselective hydrogenation of aromatic-heteroaromatic ketones

Asymmetric hydrogenation of ketone 1 using trans-RuCl(2)[(R)-xylbinap][(R)-daipen] (3) as a catalyst afforded secondary alcohol 2 quantitatively and in 99.4% ee. Further exploration of the effect of the thiazole ring substitution revealed that the catalyst was highly effective for the enantioselective hydrogenation of 5-benzoyl thiazoles, which afforded corresponding alcohols in 92-99% ee. The same protocol was applicable to a variety of aromatic-heteroaromatic ketones to generate secondary alcohols in excellent enantioselectivities. [reaction: see text]     

Asymmetric hydrogenation of enamides with Rh-BisP and Rh-miniPHOS catalysts. scope, limitations, and mechanism.

The asymmetric hydrogenation of aryl- and alkyl-substituted enamides catalyzed by Rh-BisP complex affords optically active amides with very high ee values. The Rh-MiniPHOS catalyst gives somewhat less satisfactory results. Hydrogenation of the aryl-substituted enamides with (S,S)-BisP-Rh catalyst gives R-amides, whereas the t-Bu- and 1-adamantyl-substituted enamides give S-products with 99% ee. Reaction of [Rh(BisP)(CD(3)OD)(2)]BF(4) (11) with CH(2)=C(C(6)H(5))NHCOCH(3) (5) gives two diastereomers of the catalyst-substrate complex (12a,b), which interconvert reversibly by both intra- and intermolecular pathways as shown by EXSY data. Only one isomer in equilibrium with solvate complex 11 was detected for each of the catalyst-substrate complexes 17 and 18 obtained from CH(2)=C(t-Bu)NHCOCH(3) (6) or CH(2)=C(1-adamantyl)NHCOCH(3) (7). Hydrogenation of these equilibrium mixtures at -100 degrees C gave monohydride intermediates 19 and 20, respectively. In these monohydrides the Rh atom is bound to the beta-carbon. A new effect of the significant decrease of ee was found for the asymmetric hydrogenation of CH(2)=C(C(6)H(4)OCH(3)-o)NHCOCH(3) (21), when H(2) was substituted for HD or D(2).     

Optically active cyclohexene derivative as a new antisepsis agent: an efficient synthesis of ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242)

Two new synthetic methods were established for the efficient synthesis of optically active cyclohexene antisepsis agent, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate [(R)-1: TAK-242)]. The first method involved recrystallization from methanol of the diastereomeric mixture (6RS,1'R)-7, obtained by esterification of carboxylic acid 3 with (S)-1-(4-nitrophenyl)ethanol [(S)-5)] to give the desired isomer (6R,1'R)-7 with 99% de in 32% yield. Subsequent catalytic hydrogenolysis and esterification gave (R)-1 with >99% ee. The second method employed enantioselective hydrolysis of acetoxymethyl ester 9a (prepared by alkylation of 3 with bromomethyl acetate) with Lipase PS-D to give the eutomeric enantiomer (R)-9a with excellent enantioselectivity (>99% ee) and high yield (48%). The desired (R)-1 was then obtained by transesterification with ethanol in the presence of concentrated sulfuric acid without loss of ee. Of these, the procedure employing enzymatic kinetic resolution using Lipase PS-D is the more efficient and practical preparation of (R)-1.     

Chiral alpha-branched benzylic carbocations: diastereoselective intermolecular reactions with arene nucleophiles and NMR spectroscopic studies

The chiral benzylic alcohols 1-6 were prepared and subjected to S(N)1-type displacement reactions with various arene nucleophiles in acidic medium. Under optimized conditions (HBF(4).OEt(2), CH(2)Cl(2), -78 degrees C --> r.t.) the corresponding 1,1-diarylalkanes 11-18 and 20 were obtained in good chemical yields (48-99%). The facial diastereoselectivity of the reaction is high (d.r. = 91/9-97/3) when the substrate bears a stereogenic carbon center -CHtBuMe in the alpha-position to the electrophilic carbon atom. If the starting material was enantiomerically pure, no significant racemization was observed (94% ee --> 92% ee). The reactions proceed stereoconvergently as demonstrated by the conversion of the separated diastereoisomers syn-1a and anti-1a in separate reactions to the same product syn-11 (d.r. = 97/3). Further evidence for long-lived chiral benzylic carbocations as reaction intermediates was obtained from NMR studies in superacidic medium. The chiral cation 24 was generated in SO(2)ClF as the solvent at -70 degrees C employing SbF(5) as the Lewis acid and characterized by its (1)H and (13)C NMR spectra. NOE measurements suggest a preferred conformation in which the diastereotopic faces of the cation are differentiated by the two carbon substituents R and Me at the stereogenic carbon center in the alpha-position. The hypothesis is further supported by the observation that the diastereoselectivity of the substitution reaction decreases if the bulky tert-butyl (R = tBu) substituent in the substrate 1a is replaced by a smaller ethyl group (2a, R = Et).     

Convenient syntheses of fluorous aryl iodides and hypervalent iodine compounds: ArI(L)n reagents that are recoverable by simple liquid/liquid biphase workups,and applications in oxidations of hydroquinones

Iodinations of the ortho, meta, and para fluorous arenes (R(f8)CH(2)CH(2)CH(2))(2)C(6)H(4) (R(f8)=(CF(2))(7)CF(3)) with I(2)/H(5)IO(6) in AcOH/H(2)SO(4)/H(2)O give 3,4-(R(f8)CH(2)CH(2)CH(2))(2)C(6)H(3)I (5) and the analogous 2,4- (6) and 2,5- (7) isomers, respectively. Spectroscopic yields are >90 %, but 5 and 7 must be separated by chromatography from by-products (yields isolated: 70 %, 97 %, 61 %). Reaction of 1,3,5-(R(f8)CH(2)CH(2)CH(2))(3)C(6)H(3) with PhI(OAc)(2)/I(2) gives 2,4,6-(R(f8)CH(2)CH(2)CH(2))(3)C(6)H(2)I (8) on multigram scales in 97 % yield. The CF(3)C(6)F(11)/toluene partition coefficients of 5-8 (24 degrees C: 69.5:30.5 (5), 74.7:25.3 (6), 73.9:26.1 (7), 98.0:2.0 (8)) are lower than those of the precursors, but CF(3)C(6)F(11)/MeOH gives higher values (97.0:3.0 (5), 98.6:1.4 (6), 98.0:2.0 (7), >99.3:<0.3 (8)). Reactions of 5-8 with excess NaBO(3) in AcOH yield the corresponding ArI(OAc)(2) species 9-12 (9, 85 % as a 90:10 9/5 mixture; 10, 97 %; 11, 95 %; 12, 93 % as a 95:5 12/8 mixture). These rapidly oxidize 1,4-hydroquinones in MeOH. Subsequent additions of CF(3)C(6)F(11) give liquid biphase systems. Solvent removal from the CF(3)C(6)F(11) phases gives 5-8 in >99-98 % yields, and solvent removal from the MeOH phases gives the quinone products, normally in >99-95 % yields. The recovered compounds 5-8 are easily reoxidized to 9-12 and used again.     

Efficient syntheses of four stable-isotope labeled (1R)-menthyl (1S,2S)-(+)-2-phenylcyclopropanecarboxylates

Many carbenoid cyclopropanation reactions promoted by chiral catalysts give product mixtures reflecting impressive diastereo- and enantioselectivities. Few provide a single chiral product efficiently. This limitation has been overcome in cyclopropanations of styrene and isotopically labeled styrenes with alpha-diazoacetates. Convenient syntheses on a 20 g scale of each of four chiral isotopically labeled (1R)-menthyl (1S,2S)-2-phenylcyclopropanecarboxylates (the 1-d-3-(13)C, 1,(3S)-d2, 1,2,(3S)-d3, and 1,3,3-d3 isotopomers) of better than 99% ee have been realized.