Ketenes additions

Methanesulfonyl chloride reacts with enamino ketones (104), (e.g., 151) to give good yields of the enol sulfones (e.g., 152). The analogy with ketene addition to form a-pyrones (Section IV.A) is obvious. 

Scheme 6.8 gives some examples of ketene-alkene cycloadditions. In Entry 1, dimethylketene was generated by pyrolysis of the dimer, 2,2,4,4-tetramethylcyclobutane-l,3-dione and passed into a solution of the alkene maintained at 70° C. Entries 2 and 3 involve generation of chloromethylketene by dehydrohalo-genation of a-chloropropanoyl chloride. Entry 4 involves formation of dichloroketene. Entry 5 is an intramolecular addition, with the ketene being generated from a 2-pyridyl ester. Entries 6, 7, and 8 are other examples of intramolecular ketene additions. 

The importance of the six-membered transition state for hydrogen transfer to form the ketene is clearly demonstrated by the 17-fold increase in the ketene addition product (X = NHR) in proceeding from a five-membered transition state to a six-membered transition state above/36,37 ... 

Scheme 2.153. Yb(OTF)3-promoted domino ketene addition/acyl-Claisen rearrangement.

The scope of this quinine ester-catalyzed ketene addition reaction is promising. Optically pure a- and p-hydroxycarboxylic acids of either configuration can be prepared with facility. 

A tetracyclic p-lactam 82 was formed in an attempted deprotection of 81 using lead tetraacetate <99T8457>. Other tetracyclic p-lactams (e.g. 83) have been obtained by ketene addition to the C9-N10 bond of phenanthridine <98TL7431,99TL2005>. 

Despite the success of the concerted 2s + 2a pericyclic pathway in explaining stereochemistry of numerous ketene additions, there are also examples of additions of ketenes that occur by a stepwise path.45 A number of other hetero-cumulenes also undergo 2 + 2 additions.46... 

Asymmetric addition of ketenes to aldehydes is a highly attractive synthetic access to yfi-lactones with perfect atom economy [134, 135]. This reaction can be catalyzed efficiently by using chiral amines as organocatalysts. As early as 1967 Borr-mann et al. described an organocatalytic asymmetric ketene addition to aldehydes [136] chiral tertiary amines, in particular (—)-N,N-dimethyl-a-phenylethylamine or (—)-brucine, were used as catalysts [136]. The resulting lactones were obtained with modest enantioselectivity of up to 44% ee. 

Ketene Additions. Reaction of the ketene derived from ibuprofen (Ar=p-isobutylphenyl) with (R)-pantolactone in the presence of simple tertiary amine bases in apolar solvents yielded >99% de favoring the (R,R)-ester (eq 9). The reaction is first order in each component and possesses a pronounced deuterium isotope effect knlko 4). The ketene from naproxen (Ar=2-(6-methoxynaphthyl)) affords a de of 80% under similar conditions. 

I. Kikkawa and T. Yorifuji, Synthesis, 1980, 877 as an alternative mechanism, the ester may be deprotonated, followed by elimination to form the ketene, addition of the second equivalent of reagent results in the formation of the ketone enolate. 

Rey, M., Roberts, S. M., Dieffenbacher, A., Dreiding, A. S. Stereochemical aspects of ketene addition to cyclopentadiene. Helv. Chim. Acta 1970,53,417-432. 

The penem system has always been assembled by late formation of the thiazoline ring. No attempt to obtain penems by closing the azetidinone ring as the last step has ever been reported, though this strategy is well documented on penicillins [3, 4]. Approaches based either on the dehydrative condensation of thiazoline acetic acids 4 or on ketene addition to thiazoles 5, reactions known to... 

An alternative procedure for the preparation of (111) proceeds via thermolysis of (118), which is easily synthesized by a route initially involving keten addition to an alkoxyvinyl ether. Similarly, thermolysis of (119) yields (120). The dienes (121)—(123) have been prepared from the parent diketones. ... 

The amination of ketenes to produce amides (see Scheme 1) has been subjected to a variety of computational methods, including several treatments of the solvent, with explicit roles for actively participating amine and water molecules. All the results favour a two-step process with initial addition to the C=0 bond, rather than a concerted reaction involving the C=C bond. The former involves a 1-amino-1-hydroxy ene intermediate (6), formally the enol of the amide. Inclusion of a second amine molecule lowers the barrier to the two-step reaction. Replacing the second amine with a water molecule lowers it even further, an effect which should be even greater when water is the bulk solvent. Some experimental evidence is presented for the highly hindered substrates, bis(mesityl)ketene and bis(pentamethylphenyl)ketene. Addition of primary or secondary amines clearly shows, from IR and UV spectra, the build-up and subsequent tautomerization of the intermediate enols. The kinetics of these more hindered substrates are first order in amine this is not inconsistent with the theoretical results, as such hindered ketenes may only react rather slowly with amine dimer, which is also in low concentration under the conditions used. 

Partially resolved cyclonona-1,2-diene has also been treated with t-butylcyanoketen to give optically active products. The major product (329) has a cw-relationship between the t-butyl group and the adjacent CH2, which again suggests a synchronous reaction via a 2s (allene) and 2a (keten) addition (330).- ... 

The assumption of complex 218 goes back to the very early years of enantioselective chemistry, with the aim of interpreting the catalytic action of tertiary amines in ketene additions [81]. 

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