Alkyl sulfates chirality

Alkyl halides or alkyl sulfates, treated with the salts of sulfinic acids, give sulfones. A palladium catalyzed reaction with a chiral complexing agent led to sulfones with modest asymmetric induction. Alkyl sulfinates (R SO—OR) may be side products. Sulfonic acids themselves can be used, if DBU (p. 1337) is... 

Alkylation of Etiolates with Chiral Selenonium Salts, Sulfonium Salts and Mixed Sulfates... 

An asymmetric synthesis of a-amino acids uses the alkylation of glycine enolates by mixed sulfates, e.g., methyl 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose 3-sulfate, bearing a chiral leaving group1 13-15. 

The best alkylation occurs at low temperature in the presence of 10 12 equivalents of hexamethylphosphoric triamide (HMPA). Without IIMPA, the enantiomeric excesses arc lower and the methylation is slower. Furthermore, the chiral moiety of the mixed sulfate, as well as the Schiff base moiety of the methyl glycinate, determines the outcome of the a-alkylations. 

Further application of the in-situ generation of chiral quaternary ammonium fluorides from the corresponding hydrogen sulfates has also been shown in the facile preparation of optically active esters via the alkylative kinetic resolution of secondary alkyl halides. For example, simple stirring of the mixture of 3-phenylpropionic acid, l-(l-bromoethyl)naphthalene, (S,S)-6b (X = HS04 2 mol%) and KF-2H20 (5 equiv.)... 

The industrial production of Crixivan (9 H2S04) took advantage of the chirality of (IS,2R)-aminoindanol to set the two central chiral centers of 9 by an efficient diastereoselective alkylation-epoxidation sequence.17 The lithium enolate of 12 reacted with allyl bromide to give 13 in 94% yield and 96 4 diastereoselective ratio. Treatment of a mixture of olefin 13 and V-chlorosuccinimide in isopropyl acetate-aqueous sodium carbonate with an aqueous solution of sodium iodide led to the desired iodohydrin in 92% yield and 97 3 diastereoselectivity. The resulting compound was converted to the epoxide 14 in quantitative yield. Epoxide opening with piperazine 15 in refluxing methanol followed by Boc-removal gave 16 in 94% yield. Finally, treatment of piperazine derivative 16 with 3-picolyl chloride in sulfuric acid afforded Indinavir sulfate in 75% yield from epoxide 14 and 56% yield for the overall process (Scheme 24.1).17-22... 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

The chiral octanediol in turn is converted into the corresponding cyclic sulfate by reaction with thionyl chloride and subsequent oxidation with sodium periodate and a catalytic amount of ruthenium(ni) chloride (0.1 mol%) (eq 2). In the final step, 1,2-diphosphinobenzene is lithiated by treatment with n-butyllithium (n-BuLi 2 equiv, 1.6 mol% in hexane) followed by the addition of the (3R,6R)-octane-3,6-diol cyclic sulfate (2 equiv) and a further addition of 2.2 equiv of n-BuLi. (5,5)-Ethyl-DuPHOS is obtained in a yield of over 70% [78% yield was described for the (R,R)-enantiomer by an analogous method ]. In addition to (5,5)-ethyl-DuPHOS, a variety of related bisphospholanes either linked by an ethylene bridge, or bearing other 2,5-alkyl substituents, or with opposite configuration have been prepared by this methodology. ... 

Three of the five fragments have now been assembled, and only the two amine alkylations remain. The first alkylation makes use of the epoxide to introduce the required 1,2-amino-alcohol functionality. The protected enantiomerically pure piperazine reacted with the epoxide, and the product was treated with acid to deprotect both the second piperazine nitrogen and the acetonide group left over from the earlier chiral auxiliary step. The newly liberated secondary amine was alkylated with the reactive electrophile 3-chloromethyl pyridine, and the final product was crystallized as its sulfate salt... 

The electrophile E+ can be an alkyl halide or sulfate, an aldehyde to give aldol products, or an a,P-unsatunited ester when conjugate addition is preferred. Examples from simple alkylation show that the alkyl halide can be primary alkyl, allylic 33, and even an a-bromoester or y-bromo-a,P-unsaturated ester 31. The original carbonyl compound that forms the chiral imine with SAMP or RAMP can be an aldehyde 27 or 29, a ketone (symmetrical 32 or blocked on one side 35), or an enone. Only the reagents and products are shown with oxidative [O] or hydrolytic [H20] workup. Notice that SAMP is used for the formation of either enantiomer of 28 by using different starting materials but that RAMP is used to enter the other enantiomeric series from 32. 

Sinou and co-workers [73] studied the influence of different surfactants on the palladium-catalyzed asymmetric alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl malonate in presence of potassium carbonate as base and non-water-soluble chiral ligands. Best results in activity and enatioselectivity (> 90% ee) were observed with 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as ligand and cetyltrimethylammonium hydrogen sulfate as surfactant in aqueous medium. Water-stable Lewis acids as catalysts for aldol reactions were developed by Kobayashi and co-workers [74]. An acceleration of the reaction was indicated in presence of SDS as anionic surfactants. An additional promotion could be observed by combination of Lewis acid and surfactant (LASCs = Lewis acid-surfactant-combined catalysts) as shown in Eq. (3). Surfactant the anion of dodecanesulfonic acid. 

It was observed that the rate of palladium-catalyzed allylic alkylation in water was drastically enhanced when the reaction was performed in the presence of surfactants [15]. Enantioselectivity up to 92% was obtained in the reaction of dimethyl malonate with l,3-diphenyl-2-propenyl acetate when a chiral ligand such as Binap was used in the presence of cetyltrimethylammonium hydrogen sulfate (Eq. 6) [16]-... 

Carbohydrates with more than six carbon atoms are rarely applied as auxiliaries or catalysts, as they must be prepared by multistep sequences. 1,4 5,8-Bis-anhydro-l,2-0-isopropylidene-8-methyl-6,7,9-trideoxy-a-D-glucononanose (43) was used as its methyl sulfate ester as a chiral alkylation reagent (Section D.1.1.2.2.), but no details of the preparation of the protected carbohydrate were given30. 

SL1360>. This reaction involves sequential C- then N-alkylation of the 1,3,2-dioxathiane 2,2-dioxide. C-Alkylation proceeds rapidly at room temperature but the N-alkylation step requires heating to close the ring. By this procedure, chiral nonracemic cyclic sulfates, for example 87 (Scheme 14), were converted into the enantio-merically enriched piperidines 89 with only minimal loss of enantiomeric integrity during the rather complex chemical procedure <2000SL1360>. 

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