Ethylene Grignard syntheses with

Hydroxypyrroles. Pyrroles with nitrogen-substituted side chains containing hydroxyl groups are best prepared by the Paal-Knorr cyclization. Pyrroles with hydroxyl groups on carbon side chains can be made by reduction of the appropriate carbonyl compound with hydrides, by Grignard synthesis, or by iasertion of ethylene oxide or formaldehyde. For example, pyrrole plus formaldehyde gives 2-hydroxymethylpyrrole [27472-36-2] (24). The hydroxymethylpyrroles do not act as normal primary alcohols because of resonance stabilization of carbonium ions formed by loss of water. 

Following these results with the salen complex, Bedford reported on the synthesis of a series of Fe(iii)-salen-type complexes and the use of one of them, 75 (Figure 14), for the coupling of aryl Grignard reagents with primary and secondary alkyl halides, in Et20 at 45 Fiirstner subsequently reported on the use of the tetrakis(ethylene)fer-... 

Present Day Methods. In the Grignard Synthesis (82,83), chlorobenzene [108-90-7] is converted to phenylmagnesium chloride which reacts with ethylene oxide [75-21-8] at 100°C to give (3-phenylethoxy magnesium chloride which is then decomposed with sulfuric acid to give PEA. 

Reaction of the Grignard reagent with ethylene oxide, prepared in part (b), completes the synthesis. 

Another method of preparation is similar to one used to prepare derivatives of ethylene. When phenylmethyl carbinol, which can be prepared by the Grignard synthesis, is heated with zinc chloride, styrene is formed —... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

The first total synthesis of cinchonamine (277) and 2-epicinchonamine (278) proceeds via the epimers (279), which were prepared by two independent methods.169 Scheme 28 illustrates the more efficient of the two syntheses, which involves as its first stage the condensation of 2-lithio-iV-benzenesulphonyl-indole with N-benzoylmeroquinene aldehyde (280), itself obtained by reduction of the readily available JV-benzoylmeroquinene ester (281). The critical cyclization stage [(279)— (283)+ (284)] that occurs on prolonged heating at 155 °C presumably proceeds via the immonium ion (282), since separation of the epimers of (279) followed by dehydration and cyclization affords the same mixture of (283) and (284). Finally, the hydroxyethyl group was introduced by the reaction of the Grignard derivatives of (283) and (284) with ethylene oxide.169... 

Scheme 7 displays a possibility of the synthesis of chiral 2-arylpropionic acids via the oxidative tranformation of (7 )-3-aryl-l-butenes. The requisite chiral olefins may be obtained by transition metal-catalyzed asymmetric coupling between a benzylic Grignard reagent and vinyl bromide (93 % optical yield) [28] or, more attractively, asymmetric hydrovinylation of an aromatic olefin with ethylene. The asymmetric combination of styrene and ethylene, giving the adduct 25 in 95 % ee, has been performed on a 10-kg scale with a dinuclear Ni catalyst formed from ( -allyl)NiCl2 and a unique chiral dimeric aminophosphine obtainable from (/ )-myrtenal and (5)-l-phenylethylamine [7a],... 

Reactions of Thiophen Aldehydes and Ketones.—The synthesis of bis-(4-methylpent-3-enyl)thiophens was achieved by applying the Wittig reaction to (106). A convenient method for the synthesis of (2-thienyl)ethylene oxide from thiophen-2-aldehyde and a sulphur ylide has been worked out. From 2-thenil and diethyl ketone, (107) was prepared, and its Diels-Alder reactions have been studied. The reaction of (108) with different Grignard reagents has been... 

As a variant of this first method using Grignard reagents to prepare hybrid silicones, it may be cited a very recently published synthesis of poly(sil-oxylene-ethylene-phenylene-ethylene)s by reaction of a bis-chlorosiloxane with the bismagnesium derivative of a diethynyl compound [29,30] according to the following scheme ... 

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