Staudinger reaction, enantioselective

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

Planar-chiral derivatives of 4-(pyrrolidino)pyridine (PPY) have been reported as efficient catalysts for enantioselective Staudinger reactions [75]. These chiral derivatives catalyzed the reactions between a range of symmetrical and unsymmet-rical disubstituted ketenes and a wide imine array leading to (3-lactams with good stereoselections and yields. 

V-Heterocyclic carbenes were demonstrated to be efficient catalysts for the Staudinger reaction of ketenes with /V-aryl-, /V-alkylcarbonyl imines [121]. Chiral /V-heterocyclic carbenes gave the corresponding < /.v-(3-lactams in good yields with good diastereoselectivities and excellent enantioselectivities (ee>99%). 

It has also been demonstrated that a planar-chiral azaferrocene derivative of 4-(pyrrolidino)pyridine is an excellent catalyst for the enantioselective Staudinger reaction, providing P-lactams 24 with very good stereoselection and yield <02JACS1578>. 

The absolute configuration of the structurally unique fungal metabolite mycosporins was determined in the laboratory of J.D. White by means of enantioselective total synthesis." In the endgame of the synthetic effort, the Staudinger reaction was used to elaborate the side chain. The cyclic vinyl azide was first converted to a stable vinyl iminophosphorane, which was subsequently reacted with benzyl glyoxylate to afford the corresponding Schiff base. Reduction of the imine was achieved with sodium cyanoborohydride. 

Subsequently, the ability of enantiomerically pure N-heterocyclic carbenes (NHCs) to catalyse the enantioselective Staudinger reaction has been tested. Different NHCs, obtained via deprotonation by potassium hexamethyldisilazide KHMDS in Et O of the respective parent ionic liquids, are able to promote the cycloaddition of diphenylketene and N-tosylimide giving P-lactams in elevated yields and 55-75% e.e. (Scheme 16.7) [95]. 

Ionic liquids have been proved to be efficient pre-catalysts (in solution of THF, containing 10% Cs COj) in the Staudinger reaction of arylalkylketenes with a variety of N-t-butoxycarbonyl arylimines to give the corresponding P-lactams in good yields with good diastereoselectivity and enantioselectivity (Scheme 16.8) [96]. 

Ligands have also been attached to polyethylene glycol so that they can be recovered for recycle by the foregoing methods. A phosphine isocyanate has been reacted with polyethylene glycol for use in the Staudinger reaction with alkyl azides to form a phosphine imine.173 An alkaloid has been attached to the monomethyl ether of polyethylene glycol for use in the Sharpless asymmetrical dihydroxylation of olefins. The reaction was complete in the same time, with no decrease in yield or enantioselectivity, as when the alkaloid was used by itself.174 (Asymmetrical reactions are covered in Chap. 10.)... 

An enantioselective Staudinger reaction of ketene 174 and imine 173 with imi-dazolinium-dithiocarboxylate catalyst (175) was developed by Wilhelm, et al.. Scheme 3.55 [71]. 

Scheme 3.55 Enantioselective Staudinger reaction of ketene and imine with imidazolinium-dithiocarboxylate catalyst...

In 2008, Ye and coworkers reported that chiral NHCs prepared from l-pyroglutamic acid were efficient catalysts for the enantioselective Staudinger reaction of ketenes with imines. The corresponding c/s-p-lactams 158 were obtained in good yields with good diastereoselectivities and excellent enantioselectivities (up to 99% ee) (Scheme 20.66). In the same year. Smith and coworkers independently reported the NHC-catalysed [2 + 2] cycloaddition of disubstituted ketenes and N-tosylimines. ... 

Chiral ketene fragments have proven to offer more general utility in the quest for enantioselective Staudinger reactions. In particular, ketenes containing the Evans oxazolidinone have proven to offer high diastereoselectivities in the synthesis of 3-amino-P-lactams. The ease of preparation of the carboxylic acid precursor, the low cost of the auxiliary, and the facile unmasking of the 3-amino group from the auxiliary all... 

Aza-P-lactams may be prepared by the Staudinger reaction of a ketene with an azodicarboxylate ester under catalysis by a planar chiral nucleophile. Dimethyl azodicarboxylate and diethyl azodicarboxylate performed well in this reaction. Higher azodicarboxylate esters afforded lower yields and lower enantioselectivities, while an azodicarboxamide failed to undergo reaction. 

One way to gain fast access to complex stmctures are multicomponent reactions (MCRs), of which especially the isocyanide-based MCRs are suitable to introduce peptidic elements, as the isonitrile usually ends up as an amide after the reaction is complete. Here the Ugi-4 component reaction (Ugi CR) is the most suitable one as it introduces two amide bonds to form an M-alkylated dipeptide usually (Fig. 2). The Passerini-3CR produces a typical element of depsipeptides with ester and amide in succession, and the Staudinger-3CR results in p-lactams. The biggest unsolved problem in all these MCRs is, however, that it is stUl close to impossible to obtain products with defined stereochemistry. On the other hand, this resistance, particularly of the Ugi-reaction, to render diastereo- and enantioselective processes allows the easy and unbiased synthesis of libraries with all stereoisomers present, usually in close to equal amounts. 

Ye applied his catalytic system to enantioselective p-lactam and p-lactone formations via Staudinger-like reactions with imines or ketones (Scheme 14.22). Furthermore, the reaction with benzoyldiazenes gave the corresponding oxadiazin-6-ones issue of a [4+2] cycloaddition reaction, instead of the reported [2+2] DMAP derivatives, as nucleophilic catalysts. The postulated formation of an azolium enolate upon reaction of the NHC with the ketene in these reactions was evidenced experimentally by the isolation and full characterization of such zwitterionic adducts in model reactions. ... 

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