Alkyl halides carbonyl compound

Sulfur compounds have also proven to be useful as nucleophilic acyl equivalents. The first reagent of this type to find general use was 1,3-dithiane, which on lithiation provides a nucleophilic acyl equivalent. The lithio derivative is a reactive nucleophile toward alkyl halides, carbonyl compounds and enones.116 117 118... 

The lithium derivatives described above react with electrophiles such as alkyl halides, carbonyl compounds, and thiocarbonyl compounds, resulting in the corresponding 3-substituted derivatives (190). Hydrolysis of these products by dilute acid as described in Section B,1 gives the new nonproteinogenic amino acid ester (191) along with the original amino acid ester used as the chiral auxiliary. The chemical yields are above 80% (83MI1). 

Substituted cyclobutenes 2-substituted 1,3-dienes. The reagent reacts with various electrophiles (alkyl halides, carbonyl compounds, epoxides) to give the corresponding selenides, jS-hydroxy- and y-hydroxyselenides, respectively. Three methods can be used to convert these adducts to cyclobutenes, as shown in equations... 

The lithiation of 1,3-oxathiane (296) takes place with s-BuLi at —78 °C to give 2-lithio-1,3-oxathiane (315), an analogue of 2-lithio-l,3-dithiane (161), but with lower stability487. This intermediate reacts with different electrophiles, such as alkyl halides, carbonyl compounds, benzonitrile, dimethyl disulfide, dimethyl diselenide, trimethylplumbyl acetate and trimethylsilyl, germyl and stannyl chlorides488,489. However, further deprotection of 2-substituted 1,3-oxathianes has not been reported yet. 

The cyclic a-lithio-l,3-dithiane S-oxide 406 was generated from compound 392 with n-BuLi at —10 °C and reacted with deuterium oxide, alkyl halides, carbonyl compounds and esters to afford the corresponding products 407 as mixture of diastereomers (Scheme 106)605 - 607. (V-Acyl imidazoles were better acylating agents than esters608. However, compound 406 has not been employed properly as acyl anion. Intermediate... 

Reactions of the Enolate of (1) with Electrophiles. Addition of the dioxolanones (1) to solutions of Lithium Diiso-propylamide or Lithium Hexamethyldisilazide in THF at dry-ice temperature generates the corresponding enolates which react with alkyl halides, - carbonyl compounds, and nitroalkenes almost exclusively from the face remote from the t-Bu group to give products of type (2). These can be hydrolyzed to simple ot-hydroxy-ot-methyl carboxylic acids or further elaborated. Four examples are shown in (3)-(6) in which the part of the molecule originating from lactic acid is indicated in bold. 

Acetylene itself is readily available and its first important property is its ability to form an anion (1), usually with sodamide in liquid ammonia, but also by Grignard exchange. This is one of the few carbanions available as a genuine intermediate. It reacts with alkyl halides, carbonyl compounds, and epoxides to give intermediates (2)-(4). 

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

Methyl ketones, aldols, 1,4-diketones. Japanese chemists have used this allyl dithiocarbamate for introduction of the CH3COCH2 group into various electrophiles alkyl halides, carbonyl compounds, and epoxides. Typical results are summarized in equations I-III. The reagent is first converted into the lithium salt (2) by LDA in THF at -78° in essentially quantitative yield. 

The direct replacement of chlorine in 2-chlorotetrahydrothiophene by means of MeSH leads to low yields of (339). However, reaction with diphenylacetic acid and EtjN gives the diphenylacetic ester which can be converted to (339) in excellent yield by MeSH. Alternatively, 2-mercaptotetra-hydrothiophene can be prepared by the thiourea method (CHEC-I) and methylated to give (339) <92CB1641>. Deprotonation of (339) with Bu"Li at —30°C gives the 2-lithio derivative this reacts with a variety of electrophiles (alkyl halides, carbonyl compounds) to form (340) (Scheme 69). 

Imido and oxo species react with a variety of electrophiles that include protons, alkyl halides, carbonyl compounds, and heterocumulenes. Representative reactions of oxo and imido complexes with acid and methyl bromide are shown in Equations 13.85-13.89. 

Indoles of type 30 with S02Ph, C02tBu, and CONHtBu residues in the 1-position are capable of regioselective 2-metalation, for example, with organohthium compounds metalation can be followed by reactions with appropriate electrophihc reagents (alkyl halides, carbonyl compounds, etc.) ... 

Reissert compounds 12 served as tools for some synthetically interesting transformations [196]. Deprotonation of the N-benzoyl compound 15 brings about the anion 16, which rearranges to 1-benzoylisoquinoline (17) after loss of cyanide and a 2,1-acyl shift. Electrophilic reagents, like alkyl halides, carbonyl compounds, or Michael acceptors, convert the anion 16 into 1-substituted isoquinolines with elimination of cyanide (examples 18-20) ... 

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