Leaving groups derivatives

There are dozens of new reagents that have been developed and examined for their coupling efficiency. Most are composed of a good leaving group derived from a... 

IV. Aminations via Leaving Groups Derived from Hydroxy-N-Heterocycles. 125... 

Tosylates, Mesylates, and Triflates Leaving Group Derivatives of Alcohols 514... 

TOSYLATES, MESYLATES, AND TRIFLATES LEAVING GROUP DERIVATIVES OF ALGOHOLS... 

The inorganic esters in the reactions of SOCI2 are special examples of leaving groups derived from sulfur-based acids. They are related to the sulfonates (Section 6-7). Alkyl sulfonates contain excellent leaving groups and can be readily prepared from the corresponding sulfonyl chlorides and an alcohol. A mild base such as pyridine or a tertiary amine is often added to remove the HCl formed. 

As indicated in the general scheme below, butatrienes are the first products from base-induced 1,4-elinination of hydrogen and a suitable leaving group. The butatriene in general very readily undergoes isomerization into enynes, if sufficiently "acidic" protons are available (see Chapter 11 in Ref. 3a). In aprotic media cumulenic ethers are fixed as their lithio derivatives if an excess of alkyllithium is applied... 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Two different access routes are used, whether the leaving group is carried on thiazolium derivatives such as anilinovinyl (method A), acetanilidovinyl (method B), formyl methylene, or thioformylmethylene or on the ketomethylene compound (method C). The use of acid anhydride together with pyridine has been patented (method E). 

Reactions with Acyl Garbanion Equivalents. Alkyl substituted carbanions CRXY with potential leaving groups X, Y, and acyl carbanion equivalents or CHRX (342) react with alkylboranes, providing products with mixed alkyl groups derived from both reagents. 

Conversion to a more facile, sulfur-derived, leaving group can be achieved by treatment with sodium thiosulfate or salts of thio and dithio acids (75,87). Under anhydrous conditions, boron tribromide converts the 3 -acetoxy group to a bromide whereas trimethyl silyl iodide gives good yields of the 3 -iodide (87,171,172). These 3 -halides are much more reactive, even when the carboxyl group is esterified, and can be displaced readily by cyano and by oxygen nucleophiles (127). 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

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