Syn-Chlorohydrins

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

Z)-3-Chloroallyldiisopinocampheylborane is a valuable allylating agent for aldehydes. The products are syn-chlorohydrins, which can be transformed into. it-l-alkyl-2-vinyloxiranes. a-Allenic alcohols are prepared from propargylic di i sopinocamphey Iboranes. ... 

Dibromopropene acts as a gem-allyl dianion synthon. However, the reaction is not as clean as one might desire, due to competing reductive debromination of the 1 1 products., l-Dichloro-2-propene undergoes a y-selective addition process, affording syn-chlorohydrins, but the allylindium species derived from 3-bromo-l-trimethylsilylpropene attacks aldehydes with the a-carbon. ... 

Umani-Ronchi adapted the Furstner protocol to achieve the first catalytic, enantioselective variant of this reaction. The chiral chromium salen complex was prepared from the in situ reduction of the anhydrous CrCb to CrCl2 with an excess of manganese metal, followed by complexation with the salen ligand 8 in the presence of catalytic triethylamine." Then the addition of allylic chloride (9) to aldehydes 10 to give the allylic alcohols 11 in moderate yields and in up to 95% ee. The same groups employed the same conditions for the addition of 2-butenyl bromides to aldehydes to achieve up to 83 17 syn/anti of allylic alcohol products and for the addition of 1,3-dichloropropene to aromatic aldehydes to obtain the syn chlorohydrin adduct in modest yield which were further converted to optically active vinyl epoxides. The [Cr(salen)]-catalyzed addition of propargyl halides to aromatic aldehydes allowed the synthesis of enantiomerically enriched homopropargyl alcohols in moderate yields with up to 56% ee. ... 

The solution of sodium methyl sulfide in absolute alcohol is transferred to a 3-I. three-necked flask, which is placed on a steam bath and fitted with a dropping funnel, a reflux condenser, and a mechanical stirrer. The solution is heated until the alcohol begins to boil. Heating is then discontinued and 302 g. (3.7s moles) of ethylene chlorohydrin (Note 5) is added dropwise with efficient stirring over a period of about two hours (Note 6). The reaction mixture is concentrated by distilling as much of the alcohol as possible on the steam bath. The mixture is then allowed to cool and the sodium chloride removed by filtration. The flask is rinsed, and the sodium chloride washed with three loo-cc. portions of 95 per cent alcohol. The combined filtrate and washings are concentrated on the steam bath under reduced pressure until no further distillate passes over. The residue is then transferred to a modified Claisen flask (Org. Syn. Coll. Vol. i, 125) and fractionally distilled under reduced pressure. The yield is 238-265 g. (74-82 per cent of the theoretical amount based on the sodium used) of a product boiling at 68-7o°/20 mm. 

The trimethylene chlorobromide used boiled at 142-1470. It may be prepared in 75-85 per cent yields from trimethylene chlorohydrin (p. 112) by the general method for the preparation of alkyl bromides described in Org. Syn. 1,1. 

To obtain the trimethylene chlorohydrin, the distillate from this operation is heated for about one hour on a steam bath in order to drive out most of the excess hydrogen chloride. The distillate is then fractionated under reduced pressure (Note 3) in a modified Claisen flask (Org. Syn. 1, 40). The fractionating side arm should be 25 cm. in length. The fractions collected under 10 mm. are to 55°, 55-57°, 57-65°, 65-85°, 85-105°, residue. 

The reaction of sulfoximine 6 with ClC02CH(Cl)Me proceeded readily and gave, besides 54, the chlorohydrins 57, as mixtures of the anti and syn diastereo-mers in ratios of 78 22 and 73 27, respectively, in good yields. Treatment of the mixture of chlorohydrins with DBU furnished oxiranes 58 as mixtures of trans and as isomers in ratios of 78 22 and 73 27, respectively, in good yields. 

Resin 60 was successively treated at -78 °C with n-BuLi, ClTi(NEt2)3, and benz-aldehyde in THF to afford the polymer-bound homoallyl alcohol 61. The cleavage of the linker group of 61 was achieved through treatment with ClC02CH(Cl)Me in CH2CI2 at room temperature. Thereby a mixture of chlorohydrins syn-57 and anti-57 in a ratio of 2 1 was obtained. These chlorohydrins were treated with DBU, which gave oxiranes trans-SS and cis-58 in a ratio of 2 1 in an overall yield of 34% based on sulfoximine 12. 

SYNS a-CHLORHYDRlN CHLORODEOXY-GLYCEROL 1-CHLORO-2.3-DIHYDROXYPROPANE 3-CHLORO-1.2-DIHYDROXYPROPANE a-CHLOROHYDRIN l-CHLOROPROPANE-2,3-DIOL I-CHLORO-23-PROPANEDIOL 3-CHLOROPROPANE-1,2-DIOL 3-CHLORO-1.2-PROPANEDIOL 3-CHLOROPROPYLENE GYLCOL Q P, 3 -DIHYDROXY-ISOPROPYL CHLORIDE 2,3-DIHYDROXYPROPYL CHLORIDE EPIBLOC GLYCERIN-a-MONOCHLOR-HYDRIN GLYCEROL CHLOROHYDRIN GLYCEROL-a-CHLOROHYDRIN GLYCEROL-a-MONOCHLOROHYDRIN (DOT) GLYCERYL-o-CHLOROHYDRIN MONOCHLORHYDRIN MONOCHLOROHYDRIN a-MONOCHLOROHYDRIN D U-5897... 

SYNS 4-CHLORBUTAN-l-OL (GERMAN) 4-CHLORO-l-BUTANE-OL 4-CHLOROBUTANOL TETRAMETHYLENE CHLOROHYDRIN... 

SYNS 3-CHLORPROPAN-l-OL I-PROPANOL, 3-CHLORO- TRIMETHYLENE CHLOROHYDRIN... 

SYNS CHLOROSULFONIC ACID CHLOROSULFON-IC ACID (with or without sulfur trioxide) (UN 1754) (DOT) CHROMOSULFURIC ACID (UN 2240) (DOT) MONOCHLOROSULFURIC ACID SULFONIC ACID, MONOCHLORIDE SULFURIC CHLOROHYDRIN... 

Olefin inversion (cf. 7, 338).1 Trifluoroacetyl chloride reacts with 1,2-dialkyl epoxides in DMF stereospecifically by trans opening to give u/c-chlorohydrin trifluoroacetates. These products are reduced stereospecifically by Nal to alkenes with syn-elimination to give inverted alkenes. Reductions with zinc are less selective. Inversion of olefins is also possible by addition of NCS in CF3COOH (actual reagent is trifluoroacetyl hypochlorite) followed by reduction with Nal. 

Another example of the reduction of a-chloroketone involves dynamic kinetic resolution. The reduction of an a-chloroketo ester by M. racemosus and R. glutinis resulted in optically active syn- and anti-chlorohydrin, respectively, as shown in... 

It is remarkable that even though the syn- as well as the n /-diastereomer has been observed in all the product chlorohydrins, both of them showed nearly complete optical purity. Since the optical purity of the a-chloroketoncs is only between 44% and 84% enantiomeric excess it can be concluded that reduction of the ketone proceeds with complete enantioselectivity and is independent of the adjacent center of asymmetry containing the chloro substituent. The absolute configuration of the stereogenic center bearing the hydroxyl group is S. 

O-Chlorohydrin. 3-Chtoro-1,2-propanediol 3-chloto-1,2-dihydroxypropare a-monOchlOrohydrin 3,3 -dihydroxyisopropyl chloride glycerol a-monochlorohydrin J-cbk>ropropylene glycol Epibloc. CjHjClOp mo] wt 110.54. C 32.59%, H 6.38%, Cl 32.08%, O 28.95%. CHjCI-CHOHCHjOH. Prepd from glycerol and HCI gas Conant, Quayle, Org. Syn. coll. vol. I, 294 (1941). 

A stereochemical study reported by Henry illustrated that the formation of aldehyde and formation of chlorohydrin occur with different stereochemistry, and this result implies that one process occurs by syn addition and one by anti addition of water and palladium across the olefin. This study is summarized in Scheme 16.24. Oxidation of the non-race-mic, chiral allyl alcohol in the absence of added chloride forms the (R)-(E)-alcohol, whereas reaction of the allyl alcohol in the presence of added chloride forms the product with stereochemistry resulting from the opposite mode of attack. Because it is known that the allylic alcohol binds to palladium with hydrogen bonding between the hydroxyl group and the bound chloride, Henry concluded that the reaction conducted in the presence of high concentrations of added diloride occurs by external attack of the oxygen nucleophile, while the reaction with low concentrations of added chloride occurs by insertion of the olefin into a Pd-0 bond. ... 

Coates and coworkers recently reported that boron-based Lewis acids such as BCI3 (Equation 18) and BBrs (Equation 19) react with various acyclic and monocyclic 5,c-unsaturated ketones (25) to give the halide-terminated syn-selective halo-Prins cyclization products, thus providing the sterically congested chlorohydrin (26) and bromohydrins (28) [24]. Here, the use of SnCU as a Lewis acid afforded the opposite selectivity to give the trans-chlorohydrin product (27) (Equation 18), highlighting the complementarity often possible with boron halides. 

Evans aldol reaction between the functionalized 4-phenyl-oxazohdinone 6 and 5-chloropentanal 7, securing the 1,2-syn stereochemistry " in the resultant chlorohydrin 9. The diastereoselectivity of this process is governed by the preferential formation of a (Z)-enolate and dipole minimization in the Zimmerman-Traxler transition state 8. Conversion of the aldol adduct into the corresponding mesylate was followed by reductive removal of the auxiliary to provide the hydroxymesylate 10, an advanced intermediate in the enantioselective synthesis of (-l-)-methylphenidate hydrochloride 11. The active pharmaceutical ingredient was produced in >99% ee after lecrystaUization. 

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