Enantioselective synthesis ketenes

Dai X, Nikkei T, Romero JAC, Fu GC (2007) Enantioselective synthesis of protected amines by the catalytic asymmetric addition of hydrologic acid to ketenes. Angew Chem Int Ed 46 4367 369... 

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... 

Dochnahl M, Fu GC (2009) Catalytic asymmetric cycloaddition of ketenes and nitroso compounds enantioselective synthesis of a-hydroxycarboxylic acid derivatives. Angew Chem Int Ed 48 2391-2393... 

Mermerian AH, Fu GC (2005) Nucleophile-catalyzed asymmetric acylations of silyl ketene imines application to the enantioselective synthesis of verapamil. Angew Chem Int Ed 44 949-952... 

Mermerian AH, Fu GC (2003) Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals dual activation of the electrophile and the nucleophile. J Am Chem Soc 125 4050-4051... 

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%. ... 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

W. E. Hanford, J. C. Sauer, Preparation of Ketenes and Ketene Dimers, Org. React. 1946, 3, 108-140. G. M. Coppola, H. F. Scuster, a-Hydroxy Acids in Enantioselective Synthesis, Wiley-VCH, Weinheim, New York, 1997. 

Kiyooka et al. reported that the 3i-catalyzed aldol reaction of a silyl ketene acetal involving a dithiolane moiety with y3-siloxy aldehyde resulted in the production of syn and anti 1,3-diols with complete stereoselectivity depending on the stereochemistry of the catalyst used [45b]. This methodology was applied to the enantioselective synthesis of the optically pure lactone involving a syn-l,3-diol unit, known to be a mevinic acid lactone derivative of the HMG-CoA reductase inhibitors mevinolin and compac-tin (Sch. 2). 

Kiyooka et al. have reported that stoichiometric use of chiral oxazaborolidines (e.g. (S)-47), derived from sulfonamides of a-amino acids and borane, is highly effective in enantioselective aldol reactions of ketene TMS acetals such as 48 and 49 (Scheme 10.39) [117]. The use of TMS enolate 49 achieves highly enantioselective synthesis of dithiolane aldols, which can be readily converted into acetate aldols without epimerization. The chiral borane 47-promoted aldol reaction proceeds with high levels of reagent-control (Scheme 10.40) [118] - the absolute configuration of a newly formed stereogenic center depends on that of the promoter used and not that of the substrate. 

Kobayashi s group37 developed a new enantioselective synthesis of Cis phytosphingosine using catalytic asymmetric aldol reactions as a key step (Scheme 23). The key catalytic aldol reaction of acrolein with the ketene silyl acetal 148 derived from phenyl a-benzyloxyacetate was carried out by using tin(II) triflate, chiral diamine 149, and tin(II) oxide. The desired aldol product... 

Asymmetric and enantioselective olefination reactions continue to be of interest. Wadsworth-Emmons reactions of 4-substituted cyclohexanones with the phosphonate (147), which carries a chiral benzopyrano-isoxazolidine substituent, proceed with diastereomeric excesses of 80-90% and hence provide another example of such an approach to enantiomerically pure, axially dissymmetric cyclohexylidene derivatives. A further example of trapping of in situ generated ketenes by Wadsworth-Emmons reactions to give allene carboxylates has been reported and the reaction has been extended to enantioselective synthesis by use of the optically active phosphonates (148) (Scheme 14). Moderate to good chemical yields and e.e. values up to 84% were obtained depending on the nature of (148) and the reactions conditions. 

Another applieation of photogenerated metal coordinated ketenes is based on the addition of protie nucleophiles and has been exploited in the synthesis of amino aeids and peptides. [66] As usual, the reactive intermediate is generated by photolysis of an aminoearbene complex 46, which may be a-alkylated in a previous step. The oxazolidine auxiliary applied successfully inducing asymmetry in the P-laetam formation, allowed an enantioselective synthesis of amino aeids. Sinee both enantiomers of the auxiliary may be obtained from the corresponding phenyl glycine enantiomer, natural (5) and non-natural R) amino acid esters 47 are accessible via this route (Scheme 25). A recent review on synthetical applications of chromium carbene photochemistry has been published, [li]... 

A recent enantioselective synthesis of homopenicillin took advantage of a new method for the ring expansion of penicillin [79]. Irradiation of the P-ketosulphoxonium ylide 124 resulted in the smooth formation of y-lactam 127. The reaction probably involved the formation of an acylcarbene 125 which undergoes Wolff rearrangement to the ketene intermediate 126. Intramolecular nucleophilic attack formed the new five-membered ring (Scheme 43). Homo-... 

Ye and his co-workers reported an enantioselective synthesis of 3,3,4-trisubstituted 3,4-dihydrocoumarins 150 via iV-heterocyclic carbene-catalyzed cycloaddition of ketenes 148 and o-quinone methides 147, Scheme 3.48 [64], Noteworthy, it was found that the additive methanol was crucial for the high yields and enantioselectivities. However, the rationalization for the use of the additive methanol remains unclear. 

The first highly enantioselective synthesis of the p-lactam ring with Cinchona alkaloids was demonstrated by Lectka and coworkers in 2000. They employed 10 mol% of benzoylquinine (O-Bz-Q) or benzoylquinidine (O-Bz-QD), to condense electron-deficient a-imino esters and ketenes (Scheme 15.12). To ensure in situ ketene formation (in fact a chiral ketene enolate is the reactive species.), proton sponge (PS) was used as a... 

Shao, P.-L., Chen, X.-Y, Ye, S. (2010). Formal [3+2] cycloaddition of ketenes and oxaziridines catalyzed by chiral Lewis bases enantioselective synthesis of oxazolin-4-ones. Angewandte Chemie International Edition, 49, 8412-8416. 

Later, Ye and coworkers developed a highly enantioselective synthesis of spiro-cyclic oxindole-p-lactones by a [2-1-2] cycloaddition reaction between isatins and ketenes catalyzed by A-heterocyclic carbenes (NHCs) [57]. TheA-methyl isatin 54c reacted with various aromatic ketenes 100 in the presence of an NHC precursor XXVI at -40 °C to afford the corresponding spirocyclic oxindole-p-lactones 101 in good yields and enantioselectivities, as shown in Scheme 10.36. 

Wang, X.-N., Zhang, Y.-Y, Ye, S. (2010). Enantioselective synthesis of spirocyclic oxindole-(3-lactones via n-heterocyclic carbene-catalyzed cycloaddition of ketenes and isatins. Advanced Synthesis Catalysis, 352, 1892-1895. 

Scheme 5.51 Enantioselective synthesis of carboxylic esters 156 with a tertiary stereogenic a-carbonyl center by arylation of silyl ketene acetals 155.

It must be noted that chiral thiourea catalysts have been used earlier to catalyze the asymmetric Mannich reaction. Jacobsen and Wenzel reported the enantioselective synthesis of A-Boc-protected p-amino acids from silyl ketene acetals and A-Boc-protected imines using the thiourea catalyst 123 (Scheme 11.24). Here, the chiral thiourea-derived Brpnsted acid catalyst (the application of chiral Brpnsted acids in the... 

A novel catalytic system was developed for the enantioselective synthesis of P-lactones from ketene and aldehydes by Corey group in 2006 (Scheme 1.8) [10]. 

In 2002, Fu et al. reported planar-chiral 4-(pyrrolidino)pyridine derivative (27) catalyzed enantioselective addition of amines with ketene to give acylpyroles with high ees (Scheme 2.68). They proposed the intervention of chiral Bronsted acid catalysis [129]. They employed (27) as a catalyst for the enantioselective synthesis of esters from ketenes [130]. 

Kanazawa A, Delair P, Pourashraf M, Greene AE. Convergent, enantioselective synthesis of the novel furanoditerpene (+)-taonianone through facially selective chiral olelin-ketene [2 + 2] cycloaddition. J. Chem. Soc. Perkin Trans. 11997 (13) 1911 1912. 

Hodous BL, Ruble JC, Fu GC (1999) Enantioselective addition of alcohols to ketenes catalyzed by a planar-chiral azaferrocene catalytic asymmetric synthesis of arylpropionic acids. J Am Chem Soc 121 2637-2638... 

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