Ketene iminium salts

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

The regiochemistry of ketene iminium salt cycloadditions can also differ from ketene cycloadditions. Whereas reaction of styrene with a series of ketene iminium salts gave 3-phenyI-cyclobutanones7 (60-70% yield) similar to the regiochemistry of ketene cycloadditions, reaction with a series of acrylates and a,/J-unsaturated ketones gave cyclobutanones 5 with regiochemistry opposite to what would be expected from electrostatic considerations of ketene cycloadditions.s... 

Unlike ketcnc cycloadditions, very few mechanistic studies have been carried out with ketene iminium salt cycloadditions. Differences in regiochemistry in the latter examples suggest that these reactions are not concerted and that a carbcne-type addition to the alkene leading to an intermediate such as 6 is responsible for these reactions.8... 

The ketene iminium salt cycloaddition route has been used to prepare a key intermediate 7 for the synthesis of grandisol.10... 

The use of a chiral auxiliary group on the ketene iminium salt permits the enantioselective synthesis of cyclobutanones. These salts offer a wider scope for asymmetric induction than ketenes since there are two substituents on the nitrogen of these salts which are not present on the oxygen of ketenes. Use of a chiral amide 8 or a geminal ehloroenaminc 10 permits the enantioselective synthesis of cyclobutanones 9 and 11. respectively, with enantiomeric excesses ranging from 55-97%. ... 

Derivatives other than cyclobutanones can be obtained from the ketene iminium salt by way of reduction with hydride ion of the cyclobutaneiminium salt to give cyclobutylamines. Although some stereoselectivity is observed, mixtures of stereoisomers are usually obtained, e.g. formation of 12.13... 

The intramolecular ketene iminium salt route has been used in the preparation of a key intermediate 16 for the synthesis of prostaglandins,16... 

Although the ketene iminium salt route has advantages over the ketene route, limitations of this method include the nonstereospecificity of these cycloadditions in some instances because of the nonconcerted nature of these reactions. Of greater concern is the fact that the major product from alkenes which can form a tertiary carbocation is often the Friedel-Crafts product. This method is therefore largely limited to mono- and 1,2-disubstituted alkenes. 

The stereochemical course of the annulation process has been determined by reaction of acryloyl chloride with the morpholine enamine of 4-f-butyl-2-methylcyclohexanone. The bicyclic dione was obtained in 76% yield as a 4 1 mixture of two isomers (Scheme 150). X-ray analysis of the main isomer showed that reaction had occurred by axial attack from the same side as the C-2 methyl group. In order for regeneration of the enamine system to occur under conditions of stereoelectronic control, the intermediate ketene-iminium salt presumably adopts a twist conformation. Cyclization of the ketene... 

ButenoUdes and furanes. The [2 + 2] cycloadducts (3) of alkynes with keten-iminium salts (2), readily formed from 1 (11, 560-561), undergo Baeyer-Villiger oxidation to give A -butenolides 4 exclusively. The products are readily reduced to furanes (5) by DIBAH. 

Azirenes from amides. Ketene iminium salts are generated from amide eno-lates. Further reaction with NaNj leads to 2-aminoazirenes. 

The synthesis of cyclobutanones can in some cases be accomplished more efficiently by addition of a ketene-iminium salt or a chromium carbene to an alkene. For example, under photochemical conditions, the chromium carbene 174 gave the cyclobutanone 175 as a single diastereomer (3.118). The product 175 was converted to the antifungal antibiotic (-l-)-cerulenin by way of the lactone 176. 

As an substitute for ketenes, keteniminium cations can also react with imines to afford /3-lactams. It has been found that ketoketenes give better yields of cycloadducts than do ketene iminium salts, whereas aldoketene iminium salts prevail in corresponding aldoketenes in respective reactions. In addition, ketenimines bearing an electron-withdrawing group (e.g., tosyl, cyano) on the nitrogen atom can react with imines to furnish azetidin-2-imines. ... 

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