Nucleophilic acyl synthetic equivalents

In the synthesis described in Scheme 10.10, the stereochemistry is established at an early stage. Stereoselectivity in the protonation of the enamine moiety during the hydrolysis in step B is presumably the result of preferential protonation from the less hindered side of the molecule. None of the other transformations affects these chiral centers, and the overall synthesis is stereoselective. It is interesting to note that step E in this synthesis employs a protected cyanohydrin as a nucleophilic acyl synthetic equivalent. 

The use of masked acyl anion equivalents in a synthetic protocol requires additional steps to unmask the carbonyl unit. Sometimes the deprotection procedures are incompatible with sensitive compounds thus, a direct nucleophilic acylation protocol is desirable. While C-nucleophilic carbonyl groups do not... 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

The nucleophile obtained by deprotonation of a dithiane serves as the synthetic equivalent of an acyl anion, a species that is too unstable to be prepared directly. 

Introduction. Sodium bis(trimethylsilyl)amide is a synthetically useful reagent in that it combines both high basicity and nucleophilicity, each of which may be exploited for useful organic transformations such as selective formation of enolates, preparation of Wittig reagents, formation of acyl anion equivalents, and the generation of carbenoid species. As a nucleophile, it has been used as a nitrogen source for the preparation of... 

Silyl ketene imines 21.126 (Scheme 21.18) developed by Denmark represent another group of useful nucleophilic reagents. These compounds are derived from protected cyanohydrins and thus can be viewed as acyl anion equivalents. They allow enantio- and diastereoselective construction of highly functionalised adducts 21.127, which can be further converted into useful synthetic intermediates, e.g. upon hydrolysis they produce crossbenzoin condensation products 21.128. ... 

One method that achieves the required umpoiung is using a 1,3-dithiane anion as a synthetic equivalent of the acyl anion (the Henry-Nef strategy using a nitroalkane anion offers an analogous approach, but it will not be discussed here). While the acyl anion is unstable and cannot be prepared, the 1,3-dithiane anion is stable due to the inductive withdrawal of electron density by the two sulfur atoms. The 1,3-dithiane anion can be used as a nucleophile and then converted to a carbonyl by hydrolysis. 

Asymmetric Nucleophilic Acylations with Synthetic Equivalents for the Active Aldehydes ... 

A third term which has become useful for the discussion of synthetic analysis and planning is synthon. This term refers to a structural unit which has the potential for some specific synthetic operation. Again using the example above, we are searching for a group which would serve as a nucleophilic acyl synthon that is, some structural entity that would correspond to the addition of a nucleophilic acyl equivalent to an electrophilic carbon-carbon double bond. 

Another natural carbon-carbon bond-forming process that has been adapted for use by synthetic chemists involves thiamine, or vitamin Bi, shown on p. 1058. Thiamine plays an essential role in several biochemical processes, including the biosynthesis of sugars, as we shall see in Chapter 24. Real Life 23-2 describes how thiamine also mediates sugar metabolism by converting pyruvic acid, a product of sugar metabolism, into acetyl CoA (Section 19-13). The relevant carbon-carbon bond-forming process makes use of a new kind of nucleophile derived from aldehydes and ketones, an acyl anion equivalent. 

Trost has published additional applications of a-lithiocyclopropyl phenyl sulphide, including an approach to spiro-sesquiterpenes, involving geminal alkylation, which utilizes a process that is formally the reversal of dithian-carbonyl addition(also see related studies by Marshall Synthetic applications of the highly nucleophilic methoxy-phenylthio-methyl-lithium PhSCH(Li)OMe and of the acyl anion equivalent methylthioacetic acid dianion RSCHCLOCOgLi (R = Me or Ph ) have also been described, as have synthetic procedures based on anions of a-alkylthio- or a-phenylthio-ketones and methylthiomethyl dithiocarbamates. ... 

The possibilities for assembling carbogenic structures have sharply increased in recent years with the advent of various synthetic strategies for generating the equivalents of carbon electrophiles and nucleophiles which are unavailable in structures containing simple core functional groups such as carbonyl, amino, or hydroxyl. For example, acyl anions (RCO), which for various reasons are not readily available, can be utilized in synthesis in modified or equivalent forms. Several acyl anion... 

---