Lithium tosylate displacement with

The thus established stereocenter served in the following steps. Conversion of 50 to 51 was achieved by acyl chloride formation followed by Friedel-Crafts reaction with ethylene and A1C13. Addition of the lithium enolate of t-butylacetate occurred from the less-hindered face of the cyclic ketone to give, after reduction and tosylation, adduct 52. Tosylate displacement with amine 53, esterification with methoxyacetylchloride, and addition of HC1 gave mibefradil 54. 

Spiroketalization. The synthesis of talaron ycin B (3) with four chiral centers by cyclization of an acyclic precursor presents stcrcot hcmical problems. A solution involves cyclization of a protected (3-hydroxy ketone witii only one chiral center. Because of thermodynamic considerations (i.e.. all substituents being equatorial and the anomcric effect), cyclization of 1 with HgCl, in CH,CN lollowcd by acetonation results in the desired product (2, 65% yield) with a stereoselectivity of —10 1. Final steps involve conversion of the hydroxymethyl group to ethyl by tosylation and displacement with lithium dimethylcupratc (80% yield) and hydrolysis of the acetonidc group. 

Two other purely chemical routes to chiral acetic acid have been pursued in our laboratory. In one of these, outlined in Scheme 4, stereospecifically o-deuterated or -tritiated 3,5-dimethoxybenzyl alcohol is prepared by reduction of the aldehyde with Midland s reagent (B-3-pinanyl-9-borabicyclo [3.3.1 ] -nonane, cr-pinanyl-9-BBN) (35), followed by conversion to the tosylate and reductive displacement with lithium aluminum hydride or superhydride (lithium... 

Due to the inherent C2-symmetry of 37, monotosylation occurs in good yield to provide (25, 35)-l-0-tosyl-2,3-0-isopropylidene-L-threitol (79). Subsequent protection of the the free hydroxyl group, displacement of the tosyl group with lithium diethylcuprate, deprotection. 

The mesylate-tosylate in the framework of the pyranose derivative reacted with lithium acetylide-ethylenediamine complex to give the seven-membered sultone (13) in 98% yield, as a result of displacement of a tosylate coupled with deprotonation at the mesylate producing a nucleophile and then ring formation (Scheme 6) <81CJC260>. 

So, first the reduction of the ester to the corresponding primary alcohol with lithium aluminum hydride was effected, and the alcohol was converted to the toluenesulfonate (tosylate). Displacement by bromide anion (LiBr) to produce the primary bromide was followed by another lithium aluminum hydride reduction to the final hydrocarbon (Scheme 11.65). 

The substitution of the phosphorous atom at C-5 followed by introduction into the pyranose ring has been accomplished for D-xylose [116]. The 1,2-O-isopropy-lidene a-D-xylofuranoside is tosylated at C-5 and methylated at C-3. The tosyl group at C-5 is displaced to give the 5-iodo derivative, which is displaced with triethyl phosphite, followed by reduction with lithium aluminium hydride to give the C-5 phosphine analog (reaction 4.123). 

The benzylidene derivative above is used, if both hydroxyl groups on C-2 and C-3 are needed in synthesis. This r/vzns-2,3-diol can be converted to the sterically more hindered a-cpoxide by tosylation of both hydroxy groups and subsequent treatment with base (N.R. Williams, 1970 J.G. Buchanan, 1976). An oxide anion is formed and displaces the sulfonyloxy group by a rearside attack. The oxirane may then be re-opened with nucleophiles, e.g. methyl lithium, and the less hindered carbon atom will react selectively. In the following sequence starting with an a-glucoside only the 2-methyl-2-deoxyaltrose is obtained (S. Hanessian, 1977). 

Replacement of a primary or secondary hydroxyl function with deuterium is usually carried out by first converting the alcohol into a mesylate or tosylate ester, which can then be displaced by treatment with lithium aluminum deuteride. The... 

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A -steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3l3-di-A -steroid (188) and a 6c-dj-3,5a-cyclo steroid (189). The incorporation of deuterium at the 3 -position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual S, 2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the p configuration. ... 

Deuteration at C-3 by Displacement of a 3 -Tosylate with Lithium Aluminum Deuteride... 

Deuteration at C-3 by displacement of a 3p-tosylate with lithium aluminum deuteride, 198... 

The use of lithium in liquid ammonia to reduce enones is a well-known, well-established procedure which has seen widespread use. The nucleophilic character of the -carbon is clear, and has been demonstrated in many ways. For example, reduction of enone 253 leads to displacement of tosylate and formation of the tricyclic ketone 254 [68,69]. It is interesting to note that the yield for formation of 254 is a function of the nature of the reducing agent. For example, using Li/NH3, a 45% yield is obtained, while with lithium dimethylcuprate, it is 96% [70], and via cathodic reduction, 98%. 

Chiral derivatives of hemiacetal from fluoral have been prepared by adding an alcohol to fluoral in the presence of (l )-BlNOL— Ti(0—iPr)2 or by HPLC resolution of the racemate. The displacement of the sulfonate moiety from the tosyl derivative, by an alkyl lithium aluminate, affords the trifluoromethyl ether with inversion of configuration and an excellent chirality transfer (Figure 2.49). ° ... 

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