Carbonyl compounds as electrophiles

Nucleophilic addition to the C-O double bond of carbonyl derivatives is one of the most widely used C-C-bond forming reactions in organic synthesis. The synthetic value of this process lies particularly on the stereocontrolled formation of a new C-O-chiral center when aldehydes or ketones are used. On the other hand, carbonyl derivatives themselves can serve as nucleophiles leading to new carbon-carbon bonds and thus expanding the synthetic scope of these functional groups. The explanation of the underlying basic principles in terms of reactivity and stereochemical models is beyond the scope of this book and will not be discussed in the following chapter since many textbooks cover these issues. Instead, we wish to provide the practitioner with examples that detail the delicate relationship of an individual, unique structure with its special reactivity delineated thereof 

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Aliphatic and aromatic nitriles 19 were decyanated with lithium and a catalytic amount (5%) of DTBB in the presence of different carbonyl compounds as electrophiles... 

Easy hydrolysis of hydroxycarbamates of type 105 (resultiug from the use of carbonyl compounds as electrophiles) with lithium hydroxide gave diols of type 107 iu 81-96% yield. 

Another type of sp -hybridized S-oxido functionahzed organolithium compounds has been easily prepared from chloroacetic acid (149). After a double deprotonation with lithium diisopropylamide in THF at —78°C, a DTBB catalyzed (5%) hthiation in the presence of different carbonyl compounds as electrophiles at the same temperature followed by final hydrolysis afforded the expected S-hydroxy acids 151. The corresponding intermediate 150 was probably involved in the process (Scheme 54)" . 

By a DTBB-catalyzed (5%) lithiation of chlorinated unsaturated amines 191 in the presence of a carbonyl compound as electrophile, the final hydrolysis afforded 192 as a Z/E mixture of diastereomers (Scheme 66). In this process, the corresponding sp -hybridized functionalized organolithium intermediate is probably involved. 

The use of carbon dioxide as electrophile afforded directly the thiolactone 367 in 72% yield. Finally, compounds 366, derived from the use of a carbonyl compound as electrophile, were easily cyclized under acidic conditions (85% H3PO4, toluene reflux) to yield the corresponding thioisochromans 368 in 85-97% yield. 

The reaction of dichloromethane (or its dideuterio derivative) (430) with lithium and a catalytic amount of DTBB (5%) in the presence of a carbonyl compound as electrophile in THF at —40 °C led, after final hydrolysis with water, to the corresponding 1,3-diols... 

Phenone imines 587 were lithiated with lithium and a catalytic amount of naphthalene (8%) in the presence of different carbonyl compounds as electrophiles in THF at temperatures ranging between —78 and room temperature, giving, after hydrolysis with water, the corresponding 1,2-aminoalcohols 588 (Scheme 154). ... 

Arsenic.—Carbanions of the type Ph2As(0)CHR and Ph2AsCHCH2R are obtainable by deprotonation of the conjugate acids with LiNPr and by addition of RLi to Ph2AsCH=CH2 respectively. They react with electrophiles such as carbonyl compounds or alkyl halides to give the expected products, e.g. Ph2As(0)CHRE (E = group derived from electrophile), and the arsenic moiety can subsequently be replaced by Br or by a nucleophilic moiety. In the case of products obtained from carbonyl compounds as electrophiles, the products derived from brominolysis are bromoalkenes. ° ... 

T.J.J. MiiUer, In T.J.J. Muller, editor Multicomponent Reactions 1. General Discussion and Reactions Involving a Carbonyl Compound as Electrophilic Component, The Science of Synthesis, Georg Thieme Verlag Stuttgart (2014), p 5. 

J.J. Van den Eynde and A. Mayence, A Carbonyl Compound as Electrophilic Compound — With an Amine or Analogue as One Nucleophile Component — Third Component 1,3-Dicarbonyl Compound (with Ammonia or Amines Hantzsch Pyridine Synthesis), In... 

Carbonyl Compounds as Electrophiles 1147 Table 3.1 Conditions displaying the directing effect of titanium enolates. 

The Mukaiyama aldol reaction is a highly selective cross aldol condensation using a silyl enol ether as nucleophile and a Lewis acid-coordinated carbonyl compound as electrophile. 

Recently, different a-lithioenamines 75 have been prepared by chlorine-lithium exchange from the corresponding chloroenamines 74 and reacted with electrophiles to give functionalized enamines 76. A mixture of lithium and a catalytic amount of DTBB was used as the lithiating reagent (Scheme 2.12) [67]. The process can be performed either step-by-step (lithiation-reaction with the electrophile) at -90 °C or under Barbier-reaction conditions at -40 °C. In the case of using carbonyl compounds as electrophiles, after acidic hydrolysis, a-hydroxyketones were obtained, intermediates 74 acting in this case as acyl anion equivalents [41]. 

Masked lithium homoenolates of type XII are of interest in synthetic organic chemistry and can be considered as three-carbon homologating reagents with umpolung reactivity [122]. The lithiation of the jS-chloro orthoester 147 with lithium in the presence of a catalytic amount of DTBB, under Barbier-reaction conditions, and using carbonyl compounds as electrophiles, followed by acidic hydrolysis, led to lactones 149 as reaction products, the masked lithium homoenolate 148 bang proposed as a reaction intermediate (Scheme 2.20) [123]. 

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