Grignard reagents reaction with ketals

The overall conversion of a 2-furyl ketal to a 6-substitutod l-hydroxy-2-pyridone (79) can be effected by electrolysis in methanol followed by reaction with hydroxylamine. A Grignard reagent can... 

Reaction of halides with oxide ion 0-68 Cleavage of oxonium salts 0-79 Reduction of acetals or ketals 0-92 Reaction between Grignard reagents and acetals or ketals dimerization of acetals... 

EthytidenationThe ketone (2) undergoes Wittig reaction with ethylidene-triphenylphosphorane in yields of only about 40%, with recovery of 2. The difficulty may be enolization promoted by the basic ylide. Use of the Grignard reagent from a-chloroethyltrimethylsilane results only in reduction of the carbonyl group. The problem is solved by use of 1, which reacts with 2 to give the internal ketal 3. Hydro-... 

The reaction of orthoesters with Grignard reagents provides a well known route to acetals and ketals U->-2). Eliel and Nader (1) have investigated the stereochemistry of this reaction and have concluded that it is governed by powerful stereoelectronic effects. 

When certain jS-keto-dithioesters (87) are treated with Grignard reagents, thiophilic addition occurs and 2-hydroxycyclopropanone dithioketals (88) are produced (Scheme 35) Only one isomer is obtained and a concerted cis-homo-l,4-addition has been proposed to account for the stereospecificity observed. Along somewhat similar lines, Giusti and coworkers have synthesized several cyclopropanone ketals by treating l,3-dibromo-2-propanone ketals with active metals (Table 20). Allenes are a byproduct in this reaction. Dihaloketals may also be cyclized electrolytically (Table 21). ... 

Fujioka et al. [18] prepared a new chiral a,j9-building block for use in the synthesis of optically active anthracyclinones [Eq. (3)]. Reaction of the propenyl Grignard reagent with the chiral j -tetralone gave the alkynylalcohol with an a,j -ring. The authors show one product with the indicated stereochemistry. Hydrolysis of the ketal gave the desired intermediate. 

Chiral acetals can be used as auxiliaries in the diastereoselective reactions of Grignard reagents with acyclic as well as cyclic a-keto acetals. Nucleophilic addition to the monoprotected diketone (69 equation 18) occurs with excellent stereoselectivity to generate the corresponding tertiary alcohol (70) as the major product, usually with greater than 95 5 selectivity. Removal of the ketal yields a-hydroxy ketones of high optical purity. In most examples, enantiomeric excesses of 95% and higher are observed in the resultant keto alcohols. Table 17 represents the results of additions to cyclic and acyclic substrates. 

These derivatives are prepared from the readily prepared hydroperoxide by the standard acid catalyzed ketal formation. Cleavage is achieved under basic conditions by treatment with Triton B in THF at rt, 62-87% yield. This group is stable to Grignard reagents, the Wadsworth-Emmons reaction, and reductive amination with NaBH(OAc)3. ... 

As for the diols, the symmetric compounds have found most uses for nonsymmetric diols, a versatile synthesis via silyl ketones using the SAMP/RAMP methodology has been developedl5. Both enantiomers of the simplest symmetric diol, 2,3-butanediol (11), are often used in asymmetric synthesis, mostly for the formation of acetals and ketals with carbonyl compounds and subsequent reactions with acidic catalysts (Section D. 1.1.2.2.), Grignard reagents (Section D. 1.3.1.4.) and other carbanions (Sections D. 1.5.1., D. 1.5.2.4.), and diastereoselective reductions (Section D.2.3.3.). Precursors of chiral alkenes for cycloprotonations (Section D.1.6.1.5.) and for chiral allenes (Section B.I.), and chiral haloboronic acids (Section D. 1.1.2.1.) are other applications. The free diol has been employed as a chiral ligand in molybdenum peroxo complexes used for enantioselective epoxidation of alkenes (Section D.4.5.2.2.). 

The demethylation of tropine derivatives by means of ethyl chloroformate has been extended to tropinone, which was allowed to react as its ethylene ketal. A series of iV-ethoxycarbonylnortropine derivatives have been prepared from the intermediate iV-ethoxycarbonylnortropinone by reaction with appropriate Grignard reagents. 

In model studies related to the synthesis of compactin (97) and mevinolin (98), the upper-half lactone moiety was constructed from 550 starting with an oxirane ring-opening reaction by vinyl Grignard reagent (Scheme 81) [136]. lodocarbonation of 560 followed by hydrolysis and ketalization affords isomerically pure acetonide 562, the compactin lactone synthon. 

Scheme 1. TADDOLs, Analogs, and Derivatives Thereof Constructed from +)- or (-)-Tar-trate. Aldehydes or Ketones, and a Grignard Reagent (shown here is the structure derived from (+)-(i ,i )-tartrate). Instead of tartrate acetals (R = H) or ketals (R, R H) [12], other chiral nonracemic dicarboxylates may be employed in the Grignard reaction [13] [14], Aryl = Ph can be hydrogenated to CgHn [15] [16], and the diastereoisomeric derivatives with geminal Ph/Me instead of Aryl/Aryl groups are available through the 4,5-dibenzoyl-dioxolane [14], For examples, for OH derivatizations, and for OH/Y and OH/Z substitutions, see Schemes 2 and 3.

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