Asymmetric carbonyl halides

Much of the early work in this area was reviewed by Rtidorff [1751] and Fischer [656a] in the FIAT Review of German Science these contain extremely important, otherwise unpublished, experimental data based upon the observations of Kwasnik. 

Under normal conditions of temperature and pressure, COCIF is a gas. It is colourless in both the gaseous and condensed states, and has an odour similar to, but distinguishable from, phosgene. It is non-flammable. 

The synonyms of carbonyl chloride fluoride are carbonic chloride fluoride (currently used in Chemical Abstracts), carbonyl chlorofluoride, and monofluorophosgene. The Chemical Abstracts Registry No. is [353-49-1]. COCIF is included in the European inventory of existing chemical substances (EINECS) [602a], since it was included in the core inventory [602] its EINECS number is 206-533-7. No fuli-scale commercial synthesis of COCIF has ever been operated. 

There are no recorded cases of humans being poisoned with COCIF. Consequently, the only information available is from animal experiments, most of this work having been performed during the Second World War, when looking for alternatives to the existing war gases. 

The known dose-response relationships are summarised in Table 16.1. 

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Fig. 16.4 The fundamental vibrations of a general asymmetrical carbonyl halide, COXY.

The asymmetrical, fluorine-containing carbonyl halides, COXF (X = Cl, Br or I) were first prepared and examined by Kwasnik at I.G. Leverkusen (a part of I.G. Farbenindustrie) during World War II. This work was later disclosed by RUdorff [1751], and by Fischer [656a] in the enemy-property confiscation reports, known as the FIAT Reviews of German Science. 

Ab initio calculations on COBtj 2 symmetry) and the asymmetrically substituted carbonyl halides COCIF, COBrF and COBrCl (which have only C, symmetry) have shown that when a bromine atom is present in the molecule, the highest occupied molecular orbital has bromine lone-pair character [1857aa]. In contrast to this, the HOMO of COCIF has mixed chlorine and oxygen character. The principal orbital characteristics for the most chemically significant orbitals of these molecules are given in Tables 17.3 and 17.4 it must be remembered that the low symmetry means that there is little bar to extensive mixing of the molecular orbitals. 

Asymmetric carbonylation of alkenyl halides a-methylene lactones Optically active a-mcthylene lactones can be prepared by carbonylalion of alkenyl halides such as I catalyzed by PdCI2-(R)-BINAP (5 mol %) in the presence of thallium acetate. 

The asymmetric carbonylative coupling of two different benzyl halides using disodium tetracarbonylferrate gives 1,3-diarylacetones in moderate to high yields (Scheme 4-17)The first benzyl halide is reacted with Collman s reagent at 0 °C. The second halide is added after 1 h and reacted at room temperature. The ketones can be utilized for the construction of unsymmetrically substituted hexaarylbenzenes. 

Zeolites are very useful catalysts for a large variety of reactions, from acid to base and redox catalysis [27]. Hutchings et al. reported that bis(oxazoline)-modified Cu (II)-HY catalysts are effective for asymmetric carbonyl- and imino-ene reactions and aziridination of styrene [28, 29]. Recently Djakovitch and Kohler [30-34] found that Pd(II)-NaY zeolite activates aryl halides towards Heck olefination, a-arylation of malonate, and amination reactions. It is well known that alkali-exchanged faujasite zeolites are solid base catalysts [35]. Owing to the usefulness of zeolites in organic chemistry, and our interest, we recently reported the use of modified alkali-exchanged zeolite Y, NaY zeolite [36] with electron rich copper catalyst in the Y-arylation of nitrogen heterocycles with aryl halides to afford A -arylheterocycles in excellent yields under mild conditions without the use of any additive. 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

Asymmetric introduction of azide to the a-position of a carbonyl has been achieved by several methods. These include amine to azide conversion by diazo transfer,2 chiral enolate azidation,3 and displacement of optically active trifluoromethanesulfonates,4 p-nitrobenzenesulfonates,5 or halides.6 Alkyl 2-azidopropionates have been prepared in optically active form by diazo transfer,2 p-nitrobenzenesulfonate displacement,5 and the Mitsunobu displacement using zinc azide.7 The method presented here is the simplest of the displacement methods since alcohol activation and displacement steps occur in the same operation. In cases where the a-hydroxy esters are available, this would be the simplest method to introduce azide. 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

A review entitled a-heteroatom-substituted 1-alkenyllithium regents carbanions and carbenoids for C-C bond formation has addressed the methods of generation of such species, illustrated the carbenoid reactivity of a-lithiated vinyl halides and vinyl ethers, and emphasized the synthetic potential of the carbanion species in asymmetric synthesis of a-hydroxy- and a-amino-carbonyl compounds. ... 

In contrast to halides, alcohols, and carbonyl compounds, hydrocarbons may be extremely difficult to racemize. This is particularly true for a compound with a quaternary asymmetric center, such as methylethylpropylbutylmethane, 28, which has no handle to allow one to convert the asymmetric carbon to a symmetric condition by simple chemical means ... 

A similar catalytic procedure for enantioselective formation of C-Br and C-Cl bonds has been reported recently by the Lectka group [83]. The concept of this a-halogenation of carbonyl compounds is tandem asymmetric halogenation and esterification (Scheme 3.28). Inexpensive acyl halides, 74, are used as starting... 

Also ketones and aldehydes react with the lithiated bis-lactim ether 7 with rather high asymmetric induction to give the aldol-type adduct 13 (Table 2). Like alkyl halides, the carbonyl compounds enter trans to the methyl group at C-6 i.e. (R)-configuration is induced at C-3 13). 

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