Staudinger 2 + 2-cycloaddition ketene

Staudinger, H. Ber. Dtsch. Chem. Ges. 1907, 40, 1145. Hermann Standinger (Germany, 1881-1965) won the Nobel Prize in Chemistry in 1953 for his discoveries in the area of macromolecnlar chemistry. 

Bianchi, L. Dell Erba, C. Maccagno, M. Mngnoh, A. Novi, M. Petrillo, G. San-cassan, F. Tavani, C. Tetrahedron 2003, 59, 10195. 

Also known as the Staudinger reaction. [2 + 2]-Cycloaddition of ketene and imine to form p-lactams. Other couphng partners for ketenes include olefin to give cyclobutanone and caiboi rl to give P-lactone. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 259, Springer International Publishing Switzerland 2014 

Cremonesi, G. Dalla Croce, P. Fontana, F. La Rosa, C. Tetrahedron Asymmetry 2008,19, 554-561. 

aryl R = H, alkyl, aryl, vinyl R = H, alkyl, -Cl, -Br R = alkyl, aryl, -Cl, -Br, -OR -SiMes Lewis acid = BF3-OEt2, AICI3, ZnCl2 Mechanism  

The reaction of ketenes with alkenes is assumed to occur via a concerted nonsynchronous mechanism, where the approach of the reacting partners is orthogonal. As a consequence, the bulkier substituent of the ketene will end up on the sterically more crowded face of the cyclobutanone product. There are two descriptions that explain the experimental results 1) according to the Woodward-Hoffmann rules, the LUMO of the ketene reacts antarafacially with the HOMO of the alkene that reacts suprafacially 2) the HOMO of the alkene forms a bond with the pz orbital of 

The Staudinger ketene cycloaddition was utilized as the key reaction in the synthesis of a number of bakkane natural products in the laboratory of A.E. Greene. Dichloroketene was generated in situ from trichloroacetyl chloride by zinc-copper alloy in the presence of phosphorous oxychloride. The [2+2] cycloaddition between dichloroketene and 1,6-dimethylcyclohexene gave the product in high yield and excellent regio- and diastereoselectivity. The cycloadduct was successfully converted to (+)-bakkenolide A. 

Ecteinascidin (ET)-743 is a marine natural product that exhibits potent antitumor activity. R.M. Williams and coworkers developed an approach for the synthesis of the pentacyclic framework of the molecule. At an early stage in the synthesis, they used a ketene-imine cycloaddition utilizing a chiral A/-protected ketene derivative to control the stereoselectivity. Subsequently, the chiral auxiliary was removed and the intermediate 3-lactam was converted to the target structure. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 242, Springer-Verlag Berlin Heidelberg 2009 

Ph-C=N-CH2-PMP H 62% M0OOC V /C02f-Bu 0 CHjPMP Me02C 1 C02t-Bu tu 56 44 Ph- Nv H CH2PMP 

1881—1965) won the Nobel Prize in Chemistry in 1953 for his discoveries in the area of macromolecular chemistry. 

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The Staudinger ketene cycloaddition is the nonphotochemical [2 + 2] cycloaddition of a ketene and an imine to form a P-lactam. Related ketene cycloaddition reactions include the cycloaddition of a keten with an olefin to afford a cyclobutanone, with a carbonyl to give a P-lactone, and with carbodiimides to form 4-imino P-lactams. 

STAUDINGER Ketene Cycloaddition Cycloaddition of ketenes to olefins. 

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

Between the above two methods for the synthesis of (3-lactam derivatives, the venerable Staudinger [2+2] imine-ketene cycloaddition [36] is by far the most versatile and simplest entry to the lactam fragment. Application of Staudinger... 

Palomo, C. Aizpurua, J. M. Ganboa, I. Oiarbide, M. Asymmetric Synthesis of P-Lactams by Staudinger Ketene-Imine Cycloaddition Reaction, Eur. J. Org. Chem. 1999, 3223-3235. 

Palomo, C., Aizpurua, J. M. Asymmetric synthesis of 3-amino-P-laclams via Staudinger ketene-imine cycloaddition reaction. Chem. Met. Comp. (New York) (Translation of Khim. Geterot. Soed.) 1999, 34,1222-1236. 

Palomo C, Aizpurua JM, Ganboa 1, Oiarbide M (1999) Asymmetric synthesis of P-lactams by Staudinger ketene-imine cycloaddition reaction. Eur J Org Chem 1999 3223-3235... 

The mechanism of the Staudinger ketene imine cycloaddition reaction has been the subject of much debate and has recently been reviewed. The mechanism has been studied both computationally and experimentally. Experimental evidence gathered on solution phase reactions supports a two-step mechanism, in which addition of the imine nitrogen to the ketene carbonyl group occurs to generate an intermediate zwitterion. Subsequent cyclization of the zwitterion results in formation of the key C3-C4 a-bond. 

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