Alcohol displacement with retention

In a similar vein, the keto bridge in 5 can be replaced by oxygen with retention of activity. Reduction of acetophenone derivative 19 by means of sodium borohydride leads to the corresponding alcohol (20). Reaction with phosphorus tribromide with cyanide gives... 

Stereoselectivity in the reaction of acyclic ketone 270 is different from that of the cyclic ketone 256. The acetate in 271, prepared by reduction of the ketone 270 to alcohol with LiAlH and acetylation, was displaced with Me A1 from the exo side to give 272 with retention of the stereochemistry. No racemization of benzyl cation was observed. However, reaction of 270 with MeLi gave 274. The OH group of 274 was removed with hydride from the less hindered side as shown by 275 to give 276 with... 

The closure of the lactone must be done with inversion of configuration at the alcohol centre. We should normally use a Mitsunobu reaction for this but mesylation is a good alternative. Mesylatior occurs via the sulfene with retention and then displacement of this excellent leaving group require, inversion and the cis lactone is formed. 

Thionyl chloride is the classical reagent for the preparation of alkyl chlorides from alcohols with retention of configuration. This reaction is known to proceed via alkyl chlorosulfinates (7 75) which decompose by an ion pair mechanism, but may be diverted to an SN2 displacement path by addition of pyridine171 Wagner-Meerwein rearrangements have been observed in the course of alkylchlorosulfinate decomposition, e.g. (176) - (777)172). The behavior of the isomeric chlorosulfinates (178) and (179) is consistent with competitive ion pair collapse and 1,2-alkyl shift173. ... 

Introducing azide with retention of configuration via double inversion at C-7 of the triflate 245 led to the synthesis of 7-cp/-casuarine (253). Thus, treatment of 245 with cesium triflu-oroacetate in butanone followed by potassium carbonate in methanol afforded the inverted alcohol 250. Triflation of the free hydroxyl group of 250 followed by Sn2 displacement using azide ion furnished the azide 251. Reduction of the lactone 251 followed by mesylation afforded 252. This was converted into 253 in 17% overall yield from 245 by a series of steps analogous to that used in the synthesis of 249. 

Suppression of competing nucleophilic pathways, by changing from normal solvents to fluorinated alcohols, provided evidence for homoallylic participation (40). For solvolyses of cyclohexen-4-yl tosylate (equation 4), the substitution product (IV) is important, but the bicyclic product (V) is formed in significant quantities in HFIP (Table II). The stereochemistry of the substitution product (IV Table II) supports the interpretation that a displacement of solvent with inversion of stereochemistry (ks process) occurs in nucleophilic media, changing to a homoallylic (fcA) process with retention of stereochemistry in HFIP. In acetic acid, the fcA process is just beginning, and in formic acid, the ks and fcA processes occur about equally. 

The alkylchlorosulfite intermediate then reacts rapidly with another molecule of pyridine, in the same fashion as the original alcohol, to ve a pyridinium alkylsulfite intermediate, with release of the second chloride anion. A chloride anion then attacks the substrate carbon, displacing the sulfite leaving group, which in turn decomposes to release gaseous SO2 and pyridine. (In the absence of pyridine the reaction occurs with retention of configuration. See Problem 11.55.)... 

Brook addressed this important mechanistic issue early, developing evidence for retention of configuration at silicon in the rearrangement. Based on the precedented assumption of inversion at asymmetric silicon in chloride displacement with either an organolithium or an alcohol, Brook and coworkers showed a stereochemical Walden cycle that implicated retention at silicon in the rearrangement step. Mechanistically, retention at silicon corresponds to a frontside-type displacement, consistent with the mechanism shown above. The displacement might implicate 10 as a pentacoordinate silicon intermediate rather than a transition state. 

In the reaction of the endo isomer, direct displacement of the chloride by ethyl alcohol cannot be happening, as this potential reaction leads to a product that is not observed, the exo ether (Fig. 21.15). The ether is formed, but it is formed with retention of stereochemistry, not the inversion demanded by the simple Sn2 reaction. 

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