Chloro-ketones => alkenes

Alkenes have also been converted to more highly oxidized products. Examples are (1) Treatment with KMn04 in aqueous acetone containing acetic acid gives a-hydroxy ketones. (2) 1,2-Disubstituted and trisubstituted alkenes give a-chloro ketones when oxidized with chromyl chloride in acetone RCH=CR R"—> RCOCCIR R". (3) a-Iodo ketones can be prepared by treating alkenes with... 

The above-postulated overall mechanism considers two alternative pathways depending on the nature of the acetylene derivative. Region A outlines a proposal in which the formation of the a-complex intermediate is supported by the fact that the treatment of aliphatic terminal acetylenes with FeCl3 led to 2-chloro-l-alkenes or methyl ketones (Scheme 12). The catalytic cycle outlined in region B invoked the formation of the oxetene. Any attempt to control the final balance of the obtained... 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

Since cyclobutanones are often produced by dichloroketene addition to an alkene (see Section 1.3.5.1.), a,a-dichlorocyclobutanones are very common intermediates. These can be reduced to the monochlorocyclobutanones (see Section 5.2.1.1.). It was reported249 that the C —Cl dipole has a pronounced effect on the sodium borohydride reduction of these compounds. For example, in the reduction of e ra-7-chloro-7-methylbicyclo[3.2.0]hept-2-en-6-one, the normal preference for an exo-face attack was reversed and the exo-alcohol was the major product exo-7-chlorobicyclo[3.2.0]hept-2-en-exo-6-ol exo-2d and exo-7-chlorobicy-clo[3.2.0]hept-2-en-en /o-6-ol endo-2A were obtained in a 78 22 ratio. On the other hand, when the corresponding endo-chloro ketones were reduced, the C —Cl dipole resulted in exclusive formation of the endo-alcohols endo-2b, c. 

Dehalogenation a-Bromo or a-chloro ketones are reduced by nickel boride in DMF to ketones in 70-95% yield. Wc-Dibromides are reduced to alkenes in 80-90% yield. 

OL-Alkenylcarbinols Reduction of alkynyl chlorohydrins, readily available from reaction of a-chloro ketones with lithium acetylides, with lithium aluminum hydride and sodium methoxidc results in partial reduction of the triple bond as well as a facile rearrangement to provide a-alkenylcarbinols. One useful feature is that only (E)-disubstitutcd alkenes are formed. The addition and reductive rearrangement can be conducted in a single operation. 

Athene synthesis. A new synthesis of alkenes, with the bond in a predetermined position, involves reaction of an a -chloro ketone with a Grignard reagent in ether at -60° the adduct is then treated with lithium powder and THF at -60° for 2 hours. When the temperature is raised to 20°, LiOMgBr is eliminated with formation of an alkene. Yields are moderate to good (35-99%). ... 

The alkene reduction reactions most frequently observed are of a,3-unsaturated aldehydes, ketones, acids and esters. Examples of stereospecific reductions of acyclic substrates are given in Scheme 50.148.157-159 (j, (, e formation of (123), the double bond of (122) is reduced prior to the aldehyde function. The conversion of (124) to (125) involves oxidation of the intermediate alcohol to the carboxylic acid by bubbling air into the fermentation medium. Stereospecific reductions of a, 3-unsaturated ketones may be similarly effected (Scheme 61). The reduction of the chloro ketone (126) gives (127) initially. This epimerizes under the reaction conditions, and each enantiomer is then reduced further to (128) and (129), with the predominance of the (128) stereoisomer increasing with the size of the R-group. Reduction of ( )-(130) leads to (131) and (132). ... 

This methodology has been used for an iterative synthesis of the tricyclopenta-noid hirsutene (6), as outlined in equation (II).2 Two steps in the synthesis involve Conversion of an a-chloro ketone to an alkene. This reaction was accomplished by reduction to a chlorohydrin followed by treatment with chromium(II) perchlorate.3... 

The following synthesis using an a-chloroacetic ester or an a-chloro ketone as a Cj building block possibly belongs to the same category, since only electron-deficient alkenes were eyclo-propanated to give cyclopropanes 16 but not cyclohexene. However, the reaction mechanism is not known in this case. 

Recently Ahman and Somfai [43] have used an AT-sulfonyl iminium ion-alkene cyclization as a key step in an enantioselective total synthesis of the alkaloid anatoxin A (Scheme 20). a-Hydroxy sulfonamide 55 was prepared from L-pyro-glutamic acid (cf Scheme 12) and was transformed in 6 steps into enone 112. Exposure of 112 to acid led to a mixture of bridged enone 114 and /3-chloro ketone 113. The latter compound could be converted into the desired enone with DBU. Detosylation of 114 provided the natural product (+)-anatoxin A. 

Chromyl chloride can also produce ketones, but a common side reaction is formation of an a-chloro ketone, as in the conversion of cyclododecene to a-chlorocyclododecanone (401) in 79% yield. In a subsequent reaction, the chloride moiety in 401 was reduced to give cyclododecanone in 95% yield with zinc and acetic acid. Chromyl chloride also reacts with alkenes to give a trans-chlorohydrin rather than a carbonyl compound (see sec. 2.10.C for the preparation of chlorohydrins), as in the conversion of cyclohexene to tran5-2-chlorocyclohexanol. 5 It is interesting that in this particular case (the temperature was maintained at -78°C in dichloromethane), the cis-chlorohydrin was formed. ... 

Chloromethylenetriphenylphosphorane (2). Treatment of 1 with potassium f-butoxide forms chloromethylenetriphenylphosphorane (2). Chloromelhylation of aldehydes and ketones with reagent prepared in this way results in 1-chloro-l-alkenes [(E)- and (Z)-isomers] in 60-95%, yield. If excess base is used, aromatic aldehydes give arylacetylenes, ArCHO. - ArCs=CH (40-90% yield). 

DI- and Tri-anions.—Frequently, the formation of a multi-ion is necessary in order that a specific site in a molecule can be rendered active. This is especially so where that site is less easily lithiated than others within the molecule. Such a case presents itself with the dianions (36), where reaction occurs at the more reactive carbanionic centre to give access to various useful p-hydroxy-sub-stituted compounds from conventional electrophiles. " The requisite dianions can be formed from a-chloro-alcohols and a-chloro-ketones " or alternatively by lithiation of the corresponding mercurial compounds (S ). Since the mercurial compounds can in turn be obtained from an alkene by addition of Hg(OAc)a-H2X, in excellent yield, the method provides a very versatile synthesis of p-hydroxy-compounds from alkenes. The same authors have used the new trianions (38), again generated from a mercury compound by lithium-mercury... 

The reduction of alkyl hahdes has been important in many syntheses. Sodium cyanoborohydride in HMPA will reduce alkyl iodides, bromides, and tosylates selectively in the presence of ester, amide, nitro, chloro, cyano, alkene, epoxide, and aldehyde groups [118]. Tri-n-butyltin hydride will replace chloro, bromo, or iodo groups with hydrogen via a free radical chain reaction initiated by thermal decomposition of AIBN [119]. Other functionality such as ketones, esters, amides, ethers, and alcohols survive unchanged. The less toxic tris(trimethylsilyl) silane can be used similarly [120]. 

Pyridine hydrochloride in pyridine is a mild reagent for the nucleophilic cleavage of a conjugated (but not necessarily strained) cyclopropyl ring furnishing /S-chloromethyl ketones. Photo-oxidation of mono- and di-substituted alkenes in the presence of iron (ill) chloride affords a-chloro-ketones whereas tri- and tetra-substituted alkenes suffer cleavage to form dichloro-ketones [equations (45) and (46)]." °... 

Reactions.— Lithium di-isopropylamide can effect facile reduction of a-halo-geno- (and a-alkoxy-) ketones at a rate comparable to the rate of enolization. A convenient one-pot synthesis of alkenes involves reaction of a-chloro-ketones with Grignard reagents and lithium [equation (49)]. Dehydro-... 

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