A-halomethyl

Alkyl-2-arylthiazoles and 4,5-disubstituted-2-(p-aminophenyl thiazoles were simflarly prepared from arylamides and a-halomethyl-ketones in alcoholic (239, 392, 641, 792) or acetonic solution (638, 651). 

Davis has also employed a similar procedure for the synthesis of aziridine-2-phosphonoates, involving the addition of N-(2,4,6-trimethylphenylsulfinyl)imine to anions of diethyl a-halomethyl phosphonates (Scheme 1.29) [53, 54], Aziridines... 

Cyclic a-halomethyl or a-phenylselenenylmethyl (3-ketoesters undergo one-carbon ring expansion via transient cyclopropylalkoxy radicals.360... 

Thiadiazole 5,5-dioxides (274) have been prepared by the cyclization of A(-halomethyl-sulfonyl amidines and guanidines (273) (Equation (41)) <84CHEC-I(6)463>. 

All the reactions described above rely on the electrophilic reactivity of the carbonyl C atom of the aldehyde 2. Much effort was devoted to the development of phosphaferrocenes with nucleophilic reactivity at this position. For example, transformation of the formyl group into a halomethyl function would pave the way for the preparation of Grignard or lithium derivatives by halogen-metal exchange. However, all attempts to do this were unsuccessful. 

TABLE 21. Alkaline hydrolysis of a-halomethyl-phosphonium salts658... 

Scheme 33 Synthesis of 1-Oxoethylene Peptides using a Halomethyl Ketone and a Malonatef78-80 ...

Enantioselective reductions. The neat reagent (1), prepared from ( + )-< -pinene, reduces aryl a-halomethyl ketones slowly but in high chemical yield to (R)-halohydrins in 90-96% ee, but optical induction is mediocre in the case of aliphatic a-halo ketones (35-66% ee). The chiral halohydrins are useful precursors to chiral epoxides. 

The silirane intermediate could also account for the formation of vinylsilane 89 when (trimethylsilyl)carbene is generated from dichloromethyl(trimethyl)silane and Na—K in a gas-phase reaction53. The transformations of (trialkylsilyl)carbenes, generated from (a-halomethyl)silanes by a-elimination with a strong base, may involve transient siliranes as well (equation 23 and Section III.E.l.b). 

As noted above, one difficulty which prevents versatile use of levoglucosenone 1 is its sturdy internal acetal functionality. We, therefore, designed12 a levoglucosenone carrying a handle on an appropriate position such as 6-alkoxymethyllevoglucosenone 20 so as to cleave the internal acetal functionality without difficulty. If 20 is available, its acetal linkage may be cleaved after conversion into a halomethyl derivative 21 to give a hemiacetal 22 under reductive conditions (Scheme 6). 

AIBN (1.5 2.5 mmol) in toluene (10 15 ml) was added dropwise over 8 h by means of a dropping funnel to a refluxing solution of a-halomethyl cyclic P-keto ester (0.5 mmol) and Ph4Si2H2 (0.6 mmol) in toluene (10 ml). After 12 h, the solvent was removed and the residue was purified by column chromatography (eluent hexane/ethyl acetate = 5/1 10/1) to provide the ring-expanded cyclic y-keto ester [253]. 

The synthesis of N, /V-disubstituted 2-amino-5-acylthiazoles has been reported. Starting from the thiourea 71 reaction with a-halomethyl ketones 72 furnished the thiazoles 73 in good yields. This method is useful for preparing AfN-bisaryl derivatives <02T2137>. 

These reagents react with aldehydes and ketones to form epoxides or halohydrins, and with esters to form a-halomethyl ketones. ... 

Halohydrins Opening of 1,2-epoxide ring by halogen at room temperature to afford l-halo-2-alkanols is catalyzed by this heterocycle (14 examples, 80-99%). Thus, styrene oxide gives a-halomethyl benzyl alcohols. 

More recently, the related indium-mediated radical reactions have been widely studied (Scheme 7.13).19 Indium iodide-mediated radical cyclisation was first reported by Cook et al.20 The indium-mediated 1,4-addition of alkyl radicals to (F)-but-2-enenitrile was investigated by using 1-ethylpiperidinum hypophosphite (EPHP) as a hydrogen donor in aqueous media (Scheme 7.13).21 Atom transfer radical cyclisation and reductive radical cyclisation were studied using indium and iodine.22 Indium mediated alkyl radical addition to dehydroamino acid derivatives was also reported.23 The indium-mediated radical ring expansion of a-halomethyl cyclic (3-keto esters, shown in Scheme 7.13, was achieved in aqueous alcohols.24... 

Various (1-bromoalkyl)- and some (l-chloroalkyl)cyclopropanes reacted with nitrogen nucleophiles to give the corresponding V-(l-cyclopropylalkyl)-substituted products. If the reacting center is a primary halide, i.e. a halomethyl group, the reaction proceeds without competing attack on the cyclopropane ring whether the nucleophile is azide, phthalimide i. 1049... 

Cyclooctenones 36 were made by cleavage of 8-halo- or 8,8-dihalo-l-(trimethylsiloxy)bi-cyclo[5.1.0]octanes 35, promoted by tetrabutylammonium fluoride in tetrahydrofuran. The cy-clooctenone was usually accompanied by 10-15% of the corresponding (a-halomethyl)cyclo-heptanone 37." For example, 8,8-dichloro-3,3,7-trimethyl-l-(trimethylsiloxy)bicyclo[5.1.0]oc-tane (35, X = Y = Cl) gave a mixture of 36 (Y = Cl, 43%) and 37 (X = Y = Cl, 11%). ... 

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