Tosylation stereoselective

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

A highly efficient construction of the steroidal skeleton 166 is reported by Kametani and coworkers111 in the intramolecular Diels-Alder reaction of the a, jS-unsaturated sulfone moiety of 165 (equation 117). Thus, when the sulfone 165 is heated in 1,2-dichlorobenzene for 6h, the steroidal compound 166 can be obtained in 62% yield. The compound 166 produces estrone (167) by elimination of benzenesulfinic acid and subsequent hydrogenation of the formed double bond. The stereoselectivity of the addition reflects a transition state in which the p-tosyl group occupies the exo position to minimize the steric repulsion between methyl and t-butoxy groups and the o-quinodimethane group as shown in equation 117. 

Alkynes react with electrophilic selenium reagents such as phenylselenenyl tosylate.155 The reaction occurs with anti stereoselectivity. Aryl-substituted alkynes are regioselective, but alkyl-substituted alkynes are not. 

Chapter 1 deals with alkylation of carbon nucleophiles by alkyl halides and tosylates. We discuss the major factors affecting stereoselectivity in both cyclic and acyclic compounds and consider intramolecular alkylation and the use of chiral auxiliaries. 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

Equation (9)).49,49a 49d The solvent (THF or 1,4-dioxane) and reaction temperature (85 °C) are the keys to a smooth relay of the unit processes and high stereoselectivity of 220. The electron-withdrawing tosyl group of the imine is important for this reaction, since the same reaction of 218 with 7V-(4-chlorobenzylidene)aniline instead of 219 afforded the cyclopropane 221 in 92% yield. 

Considering the monoaminomercuration-demercuration of 1,4-hexadiene with /V-me-thylaniline leads to V-methyl-lV-(l-methylpent-3-enyl)aniline, the stereoselective synthesis of /V-alkoxycarbonyl or /V-tosyl s-2,5-dimethylpyrrolidine from the same diene has been explained172 on the basis of an initial amidomercuration reaction on the terminal bond followed by the second addition of mercury(II) salt to the internal double bond, on the less sterically hindered site (equation 171). 

The cathodic cleavage of CX- to CH-bonds can be achieved with a variety of substituents X, such as Hal, NR3+, PR3+, OTos, or epoxides. Generally, good yields, a high potential selectivity, and often good stereoselectivities are encountered (see also Chapters) [117-123]. Chemical reactions for similar conversions, which are well worked out, especially with regard to yield and selectivity, are the reduction of tosylates with LiAlH4 and halides with... 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

If an organomagnesium reagent bears a remote leaving group, cyclizations can be achieved. Starting from the tosylate 133, a stereoselective substitution using CuCN-2LiCl... 

On the other hand, optically active 43 and 44 were synthesized as follows.401 Treatment of 2,3,4-tri-0-benzyl-l,5-di-0-tosyl-D-arabinitol (277) with three equimolar proportions of methylenetriphenylphos-phorane gave the cyclic phosphorane (278), which was stereoselectively converted into the cyanohydrin (279) by way of the corresponding C-methylene and inosose derivatives. Compound 279 was converted into 43 and 44 by way of the corresponding carboxylic acid (280), and unsaturated nitrile (281), respectively. Compound 39 was derived from the inosose (282), obtained from quebrachitol, through a 21-step conversion.402 Introduction of a hydroxymethyl group into 282 was accom-... 

T. Mukaiyama, Y. Hashimoto, Y. Hayashi, and S.-l. Shoda, Stereoselective synthesis of a-ribonucleosides from 1-hydroxy sugars by using 2-fluoropyridinium tosylate, Chem. Lett 557 (1984). 

Azetidine-2-carboxylic acid (2) is commercially available. It is readily prepared as the racemate by refluxing 2,4-dibromobutyric acid ester with benzhydrylamine in acetonitrile. If benzyl 2,4-dibromobutyrate is treated with benzhydrylamine, the resulting benzyl TV-benz-hydryl-D,L-azetidine-2-carboxylate is hydrogenolytically processed to D,L-azetidine-2-car-boxylic acid in a one-step reaction. 101,107 Resolution of the racemate can be performed by the method of Vogler 108 via fractional crystallization of the Z-D,L-Aze-OH-H-Tyr-N2H3 salt thereby the salt of the D-imino acid precipitates first from methanol. 96 A stereoselective synthesis of A-tosyl-L-azetidine-2-carboxylic acid can be achieved by a two-step reaction from N-tosyl-L-homoserine lactone. 94 ... 

Enantiomerically pure pipecolic acid (6) is accessible essentially by two well-established synthetic routes (i) cyclization of l- or D-lysine by reaction with disodium nitrosyl-pentacyanoferrate(II) with preservation of configuration at C2 215 216 (ii) ring closure of A ,Ae-bis(A-nitroso-A-tosyl) derivatives of l- or D-lysine, again with retention of chirality at C2. 217 Stereoselective synthesis of pipecolic acid derivatives, substituted in position 4, is achieved using the aza-Diels-Alder reaction of imines with dienes 218-220 or via an ene-iminium cyclization. 221 222 ... 

Analogously to AAla from Ser, AAbu can be derived from Thr by using essentially the same methods.1"-104 However, because of the possibility of E- and Z-isomers with AAbu, either stereoselective synthesis or separation of isomers must be taken into consideration. Srinivasan et al. 89 reported detailed stereochemical studies on the 3-elimination of Thr derivatives. Lee et al. 122 confirmed the stereospecific formation of AAbu from O-tosyl Thr derivatives the Z-isomer from the threo type and the E-isomer from the erythro type. If DSC is used for direct elimination, only the Z-isomer 57 is formed from Z-Thr-OMe 56 in 70% yield (Scheme 19). 

Asymmetric 1,3-dipolar cycloaddition of nitrones to ketene acetals is effectively catalyzed by chiral oxazaborolidines derived from N-tosyl-L-a-amino acids to afford 5,5-dialkoxyisoxa-zolidines with high regio- and stereoselectivity [70] (Eq. 8A.46). Hydrolysis of the N-O bond of the resulting chiral adducts under mild conditions yields the corresponding [1-amino esters quantitatively. 

Recently, Maeda and coworkers utilized the (S, S) -le-catalyzed asymmetric alkylation of phenylglycine-derived Schiffbase 42 (R1 = Ph) for the stereoselective synthesis of a 4-hydroxy-2-phenylproline framework [27]. After hydrolysis and transesterification, the resulting (S)-49 was derivatized to its N-tosylate 50. Subsequent treatment of 50 with Br2 in CH2C12 resulted in the formation of y-lactone 51 with high diastereos-electivity this was then treated with NaH in methanol to give essentially pure (2 S,4R)-4-hydroxy-2-phenylproline derivative 52 in 80% yield from 50 (Scheme 5.25). 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

A characteristic feature of the dianhydrohexopyranoses is their steric rigidity. Consequently, they usually react with high and predictable regio-and stereoselectivity, mainly by diaxial cleavage of the oxirane ring. Thus, they became versatile starting materials for synthesis of various carbohydrates as well as noncarbohydrate structures. The most important compounds are l,6 3,4-dianhydro-2-0-tosyl-/l-D-galactopyranose (146), the manno epoxide 143, the altro epoxide 159, and the 2,3- and 3,4-anhydro-a//o epoxides 138 and 139. The tosyl epoxide 146 (for its crystal structure,... 

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