Tosylates elimination

KOBu -DMF is the preferred reagent in tosylate elimination reactions with no accompanying substitution reactions [(—)-menthyl tosylate, (—)-bornyl tosylate, (-t-)-carvomenthyl tosylate] the tosylate of (-l-)-dihydrocarveol (164) gives a good yield (85%) of (-)-p-mentha-3,8-diene and (—)-p-mentha-2,4(8)-diene as sole products, presumably via base-catalysed rearrangement of isolimonene. ... 

Base-promoted tosylate elimination from (—)-bornyl tosylate is reported to yield bornene as the only hydrocarbon using potassium t-butoxide in DMF, in DMSO, and in benzene-(18-crown-6), although a second report of reaction in DMSO detects some camphene. ... 

Dimethyl sulphoxide has recently been used for tosylate elimination reactions [131 ], It is not clear whether this is a simple Ei process. The nucleophilic reactivity of dimethyl sulphoxide (p. 46) suggests the possibility of an indirect mechanism, with preliminary Sn2 substitution of the tosylate group by the oxygen atom of the reagent. This would permit elimination of an equatorial tosylate via the more favourably oriented axial oxysulphonium ion (c/. p. 47). 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

Similarly, when a nucleophile is added under basic conditions to a solution of dimethyl 2-(tosylmethyl)fumarate in THF at room temperature, a mixture of 8 278 2 products is obtained. Thus, reaction of sodium diethyl l-(ethoxycarbonyl)methylphosphonate with this sulfone affords exclusively the 8, 2 product in 58% yield. This reaction may be regarded as a Michael addition-tosyl elimination process. ... 

An alternative way to HMHM-structures such as 32 is shown in Scheme 6. The Co-symmetrical ditosylate 24 is converted into the mono-acetonide 29 which forms the epoxide 30 on treatment with base. The cuprate attack on the epoxide generates a second epoxide 31 via tosylate elimination. With excess cuprate 31 is opened to give 32 directly (4). 

In the cyclopentyl series, 5y/i-elimination occurs from a planar transition state, but a/in -elimination is slightly distorted from a dihedral angle of 180°. Consequently, the preference for n/m -elimination is less marked in the five-than in the six-membered ring systems (Table 12). With the small neutral base trimethylamine, electrostatic forces of attraction between the sulphonate ester and the partially neutralised base balance the normal preference for n/iti-elimination and the reaction is almost non-stereospecific. None of the reactions follows the carbanion mechanism, as general base catalysis is observed for the 2-p-tolylsulphonylcyclopentyl tosylate elimination and the studies on 2-phenylcyclopentyl tosylates revealed large isotope effects (A h/A d) and p values smaller than in the 2-phenylethyl series (see Table 9, p. 209) " . 

Now let s draw the forward scheme. The 3° alcohol is converted to 2-methylpropene using strong acid. Anti-Markovnikov addition of HBr (with peroxides) produces l-bromo-2-methylpropane. Subsequent reaction with sodium acetylide (produced from the 1° alcohol by dehydration, bromination and double elimation/deprotonation as shown) produces 4-methyl-1-pentyne. Deprotonation with sodium amide followed by reaction with 1-bromopentane (made from the 2° alcohol by tosylation, elimination and anfi -Markovnikov addition) yields 2-methyl-4-decyne. Reduction using sodium in liquid ammonia produces the E alkene. Ozonolysis followed by treatment with dimethylsulfide produces an equimolar ratio of the two products, 3-methylbutanal and hexanal. 

Sulfonate esters are subject to the same limitations as alkyl halides Competition from elimination needs to be considered when planning a functional group transforma tion that requires an anionic nucleophile because tosylates undergo elimination reactions just as alkyl halides do... 

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

Although there is usually a preference for anti elimination in acyclic systems, syn elimination is competitive in some cases. In acyclic systems, the extent of anti versus syn elimination can be determined by use of stereospecifically deuterated substrates or by use of diastereomeric reactants which will give different products by syn and anti elimination. The latter approach showed that elimination from 3-phenyl-2-butyl tosylate is a stereospecific anti process. ... 

Ester eliminations are normally one of two types, base catalyzed or pyrolytic. The usual choice for base catalyzed j5-elimination is a sulfonate ester, generally the tosylate or mesylate. The traditional conditions for elimination are treatment with refluxing collidine or other pyridine base, and rearrangement may occur. Alternative conditions include treatment with variously prepared aluminas, amide-metal halide-carbonate combinations, and recently, the use of DMSO either alone or in the presence of potassium -butoxide. 

The use of mesyl chloride for the dehydration of C-11 alcohols has already been mentioned, and mesylates can certainly be intermediates at least in the a-series. The preference for a coplanar trans arrangement is demonstrated by the well-known elimination reactions of tosylates of epimeric 20-alcohols (ref. 185, p. 616), although this does not restrict the usefulness of the reaction, and in some cases (sulfonates of 1 la-alcohols, for example) cw-elimination occurs (ref. 216, p. 293 ref. 224, 225, 226). 

A -Oleflns in the 5a-series are frequently formed by elimination from the tosylates of 3j5-alcohols. Contamination with A -compound is common, and puriflcation via a derivative (e.g. dibromide) may be necessary (see page 343). A 2-methyl substituent increases the selectivity ... 

It has been claimed that the elimination of tosylates of 3a-alcohols in 5jS-series gives 3-oleflns with high selectivity. However, the homogeneity of these products is questionable, in view of recent findings concerning the ehmination of 3-chloro compounds (see below) and Fieser s results with the elimination of methyl lithocholate tosylate (ref. 232, cf. ref. 233). Neutral alumina may also be used to effect elimination of tosylates of 3j5-alcohols if the alumina is pretreated with potassium hydroxide the inverted alcohol is the predominant product. 

Tosylates also undergo elimination upon treatment with lithium salts in amide solvents. The a,/ -unsaturated ketone (106) is formed from the a-hy-droxy ketone tosylate in a fashion analogous to a-halo ketone eliminations. 

Dimethyl sulfoxide (DMSO) has been used to effect the elimination of sulfonates at elevated temperatures (see, for example, ref. 237). Benzene-sulfonates are recommended. The elimination of a variety of sulfonates proceeds readily in this medium in the presence of potassium /-butoxide. A -Compounds have been formed at 100°, but heating is not necessary. The effects of temperature change, orientation of the hydroxy group and changes in the sulfonate employed have been examined. The principal side reaction appears to be formation of the original alcohol (uninverted), particularly with equatorial mesylates at low temperatures it is minimized with axial tosylates. 

The elimination of water from a fluorinated compound generally follows a reaction path similar to that of its nonfluorinated counterpart, although the presence of the highly electronegative fluorine atoms may have unexpected effects Various monofluoro alcohols can be dehydrated via their tosyl esters at 75 C by using potassium rert-butoxide [80] (equation 50)... 

Base-promoted E2 elimination involves simultaneous loss of and X from neighboring carbons. Applying this rule to 2-methylcyclohexyl tosylate suggests that two different products might form, but the actual situation is more complicated. One tosylate isomer gives only one of the two possible alkenes, while the other gives both. 

Examine all of the low-energy (within. 004 au or 3 kcal/ mol of the lowest-energy conformer) conformers of cis-2-methylcyclohexyl tosylate. Identify every conformer that can undergo anti elimination of OTs and H+, and predict the alkene that will be produced. What alkenes will be obtained from the cis tosylate ... 

Another interesting question concerns the rate at which each tosylate undergoes elimination. A tosylate sample contains molecules with several different conformations. The size of each conformer population depends on conformer energy, and the more reactive tosylate will probably be the one with the largest population of reactive conformers, i.e., molecules whose geometries allow anti elimination. Which tosylate, cis or trans, will have a larger population of reactive conformers Explain how you reached this conclusion. 

Mesylates and tosylates may be used as variants of the 0-sulfate ester. For instance, 55% of aziridine 7 was obtained from base-mediated cyclization of amino mesylate 6. In comparison, the classic Wenker protocol only gave 3% of 7. In another instance, A-tosyl amino alcohol 8 was tosylated to give 9, which was transformed to aziridine 10 in 64% yield, along with 29% of the P-elimination product due to the presence of the ester moiety. Likewise, aziridine 12 was assembled from tosylate 11 in two steps and 60% yield. ... 

The ketoxime derivatives, required as starting materials, can be prepared from the appropriate aromatic, aliphatic or heterocyclic ketone. Aldoximes (where R is H) do not undergo the rearrangement reaction, but rather an elimination of toluenesulfonic acid to yield a nitrile. With ketoxime tosylates a Beckmann rearrangement may be observed as a side-reaction. 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

The tosylate of (2>RP35)-3-phenyl-2-butanol undergoes E2 elimination on treatment with sodium ethoxide to yield (Z)-2-pheny)-2-butene. Explain, using Newman projections. 

Because the Williamson synthesis is an S 2 reaction, it is subject to all the usual constraints, as discussed in Section 11.2. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore be synthesized by reaction between the more hindered alkoxide partner and less hindered halide partner rather than vice versa. For example, terf-butyl methyl ether, a substance used in the 1990s as an octane booster in gasoline, is best prepared by reaction of tert-butoxide ion. with iodomethane rather than by reaction of methoxide ion with 2-chloro-2-methylpropane. 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

Alternatively, the hydroxy group can be converted to the tosyl ester168 or replaced by chlorine108,169 followed by a base-catalyzed elimination. 1-Benzoxepin-5-(4//)-one is reduced with cerium(III) chloride/sodium borohydride to the hydroxy derivative. After conversion to the p-toluenesulfonate, the double bond is formed in 2 upon treatment with potassium tert-pen-toxide.168... 

Under acidic conditions, dienone tosylhydrazones 5 cyclize to 1 -tosyl-6,7-dihydro-l//-l,2-diazepines 6,l04a which on treatment with sodium ethoxide eliminate the elements of/Moluenesul-finic acid to yield an equilibrium mixture of the tautomeric 3//-1,2-diazepines 7 and 8.104b... 

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. 

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