Diastereoselective synthesis halides

This method was applied to the diastereoselective synthesis of vinyl ethers from readily available a-alkoxy aldehydes9. Reasonable selectivity in favor of the syn-adduct is observed when the stannyl anion is modified by softer metal salts such as zinc halides or copper(I) bromide. 

Azetidines are compounds of interest in the field of agricultural and pharmaceutical chemistry. They are also useful as monomers and cross-linkers in polymer industry. Due to ring strain associated with it, azetidines are also useful S5mthons in organic chemistry. The common methods for S5mthesis of azetidines are cyclizations of y-amino alcohols, y-amino halides, 3-amino allenes, reactions of 1,3-dielectrophiles with amines, metal-catalyzed cyclizations in diazocarbonyls, cycloaddition reactions, and reduction of 2-azetidinones. There are several reports in literature on the S5mthesis of azetidines in aqueous media. A diastereoselective synthesis of azetidines is reported by the reaction of azazirconacyclopentane derivatives with iodine followed by treatment with aqueous potassium carbonate [26]. 

Alkenylcarbene complexes react with in situ-generated iodomethyllithium or dibromomethyllithium, at low temperature, to produce cydopropylcarbene complexes in a formal [2C+1S] cycloaddition reaction. This reaction is highly diastereoselective and the use of chiral alkenylcarbene complexes derived from (-)-8-phenylmenthol has allowed the enantioselective synthesis of highly interesting 1,2-disubstituted and 1,2,3-trisubstituted cyclopropane derivatives [31] (Scheme 9). As in the precedent example, this reaction is supposed to proceed through an initial 1,4-addition of the corresponding halomethyllithium derivative to the alkenylcarbene complex, followed by a spontaneous y-elimi-nation of lithium halide to produce the final cydopropylcarbene complexes. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

Stereoselective synthesis of the 1,3-amino alcohol moiety is possible starting from N-tert-butyldimethylsilyloxycarbonyl derivatives of allylic halides 5 through a ScN cyclization. Thus, methyl ( )-2-tm-butyldimethylsilyloxycarboiiylamino-6-chloro-4-hexenoatc (5, R = COOCH3), treated with 2 equivalents of silver fluoride in acetonitrile, gives a mixture of the cis- and trans-tetrahydro-2//-l,3-oxazin-2-oncs 6 in 65% yield, although in moderate diastereoselectivity,9c. 

Asymmetric Synthesis of a-Amino Acids. Chiral ketimines prepared from the title ketone and glycinates can be deprotonated and treated with electrophiles, such as alkyl halides (eq 1), or Michael acceptors, to give a-subsdtuted a-amino acids with moderate to excellent levels of diastereoselectivity. 

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

The Heck reaction is applicable to the synthesis of benzo-fused heterocycles including indolines, 1,2-dihydroquinolines, and benzopyrans. Influence of reaction conditions on diastereoselectivity is witnessed in the cyclization leading to geissoschizol and its isomer. Reaction of 2-cyanothiophene with aryl halides introduces the aryl group to the 5-position."... 

Pinacol formation from carbonyl compounds promoted by Smij continues to interest chemists. In the presence of methyl chloroformate the products are cyclic carbonates. In a cyclitol synthesis the diastereoselectivity for cyclization is found to be dependent on the a-substituents of the aldehyde groups. Lithium halides (chloride, bromide) have a profound effect on the reactivity of Sml2 and the pinacol coupling is favored. The reduction and pinacol coupling of ketones in THF is accelerated by MejSiCl (reaction time from hours reduced to a few minutes)." ... 

Studies in the nineteen-eighties revealed that some Maimich-type reactions of imines with silyl enolates can be controlled with high diastereoselectivity, and that use of a chiral auxiliary enables highly enantioselective synthesis of -aminocarbo-nyl compounds [186]. Some Lewis acids, for example TMSOTf and zinc halides, were also found to be effective in catalytic quantities [187-190] although the original method requires a stoichiometric amount of TiCU [185]. In the last decade, further progress has been made by development of new acid catalysts. 

---