Asymmetric formation

Shibasaki M, Grdger H (1999) Chiral Heterobimetallic Lanthanoid Complexes Highly Efficient Multifunctional Catalysts for the Asymmetric Formation of C-C, C-O and C-P Bonds. 2 199-232... 

Fischer DF, Xin ZQ, Peters R (2007) Asymmetric formation of allylic amines with N-substimted quaternary stereocenters by Pd -catalyzed Aza-Claisen rearrangements. Angew Chem Int Ed 46 7704-7707... 

Xin ZQ, Fischer DF, Peters R (2008) Catalytic asymmetric formation of secondary allylic amines by Aza-Claisen rearrangement of trifluoroacetimidates. Synlett 1495-1499... 

Zajac M, Peters R (2007) Catalytic asymmetric formation of P-Sultams. Org Lett 9 2007-2010... 

Scheldt and co-workers have also accessed enolate equivalents from enals to furnish cyclopentanes 236 asymmetrically. Formation of the enolate equivalent from enals 235 with the NHC, followed by an intramolecular Michael reaction and 0-acylation, gives the lactone products 236, which are readily opened by either alcohols or amines to generate functionalised cyclopentane derivatives 237 in excellent ee. 

Schreiber et al.47 have described a mathematical model that combines enantiotopic group and diastereotopic face selectivity. They applied the model to a class of examples of epoxidation using several divinyl carbinols as substrates to predict the asymmetric formation of products with enhanced ee (Scheme 4-28). 

Hetero Diels-Alder reactions are very useful for constructing heterocyclic compounds, and many important chiral molecules have thus been synthesized. Although the retro Diels-Alder reaction does not itself involve the asymmetric formation of chiral centers, this reaction can still be used as an important tool in organic synthesis, especially in the synthesis of some thermodynamically less stable compounds. The temporarily formed Diels-Alder adduct can be considered as a protected active olefin moiety. Cyclopentadiene dimer was initially used, but it proved difficult to carry out the pyrrolytic process. Pentamethyl cyclopentadiene was then used, and it was found that a retro Diels-Alder reaction could easily be carried out under mild conditions. 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

Scheme 60 Catalytic asymmetric formation of epoxides from a,p-unsaturated ketones...

Chiral phosphoric acids mediate the enantioselective formation of C-C, C-H, C-0, C-N, and C-P bonds. A variety of 1,2-additions and cycloadditions to imines have been reported. Furthermore, the concept of the electrophilic activation of imines by means of phosphates has been extended to other compounds, though only a few examples are known. The scope of phosphoric acid catalysis is broad, but limited to reactive substrates. In contrast, chiral A-triflyl phosphoramides are more acidic and were designed to activate less reactive substrates. Asymmetric formations of C-C, C-H, C-0, as well as C-N bonds have been established. a,P-Unsaturated carbonyl compounds undergo 1,4-additions or cycloadditions in the presence of A-triflyl phosphoramides. Moreover, isolated examples of other substrates can be electrophil-ically activated for a nucleophilic attack. Chiral dicarboxylic acids have also found utility as specific acid catalysts of selected asymmetric transformations. 

Asymmetric formation of /i-lactams (38) in high ee has been achieved by reaction of achiral imines (36) with a ternary complex of achiral lithium ester enolate (35), achiral lithium amide, and a chiral ether ligand (37) (in either stoichiometric or catalytic amount) 45 the size and nature of the lithium amide have a considerable effect on the enantioselectivity of the ternary complex. 

Chiral pyrrolidine derivatives, proline, and amino acid-derived imidazolidinones mediate the asymmetric epoxidation of ,/i-unsalurated aldehydes. Protected a,a-diphenyl-2-prolinol catalyses the asymmetric formation of 2-epoxyaldehydes, with hydrogen peroxide or sodium percarbonate as the oxygen sources, with 81-95% conversion with up to 96 4 dr and 98% ee.204... 

In summary, these procedures for asymmetric formation of C-F bonds are efficient but still require use of stoichiometric amounts of organocatalyst. Thus, an extension of this process toward catalytic synthesis with reduced catalytic amounts of alkaloids is highly desirable. 

Under optimized reaction conditions this two step synthesis for asymmetric preparation of /1-lactams is performed as follows. First, the organocatalyst 46 is added as a shuttle base to a solution of the acid chloride, 47, and the proton sponge , 49, at low temperature. Within a few minutes the soluble ketene and the hydrochloride salt, 49 HC1, as a white precipitate, are formed. Subsequently, the imino ester 44 is added to this solution at —78 °C, which results in the asymmetric formation of the /Mactam. Thus, the alkaloid 46 acts both as a dehydrohalogena-tion agent and as an organocatalyst for subsequent lactam formation [49, 52]. 

Simple dipeptides bearing a primary amino N-terminus catalyse direct asymmetric intramolecular aldol reactions in up to 99% ee.115 These simple catalysts such as L-Ala-L-Ala and L-Val-L-Phe can also promote the asymmetric formation of sugars, further suggesting a possible role in prebiotic chemistry. 

Benovsky P, Stephenson GA, Stille JR (1998) Asymmetric formation of quaternary centers through aza-annulation of chiral P-enamino amides with acrylate derivatives. J Am Chem Soc 120 2493-2500... 

Chiral auxiliaries are optically active compounds which are used to direct asymmetric synthesis. The chiral auxiliary is temporarily incorporated into an organic synthesis which introduces chirality in otherwise racemic compounds. This temporary stereocentre then forces the asymmetric formation of a second stereocentre. The synthesis is thus diastere-oselective, rather than enantioselective. After the creation of the second stereocentre the original auxiliary can be removed in a third step and recycled. E. J. Corey in 1975, B. M. Trost in 1980 and J. K. Whitesell in 1985 introduced the chiral auxiliaries 8-phenylmenthoT (1.40), chiral mandelic acid (1.41) and frans-2-phenyl-l-cyclohexanoT (1.42), respectively. 

Shibasaki, M. and Groger, H. (1999) Chiral heterobimetallic lanthanoid complexes highly efficient multifunctional catalysts for the asymmetric formation of CC CO and CP bonds. Topics in Organometallic Chemistry, 2 (Lanthanides) 199-232. 

Guijar, M K, Kumar, P, Rao, B V, Stereocontrolled synthesis of spirocyclopropane sugars and their application to asymmetric formation of tertiary chiral centres a route to 2,2 -diaIkylated pyranose subunit (C-18-C-23) of lasonolide A, Tetrahedron Lett., il, 8617-8620, 1996. 

Two representative organocatalytic reaction systems can be considered for nucleophilic a-substitution of carbonyl compounds, the issue of this chapter. One involves the in situ formation of a chiral enamine through covalent bond between organo-catalyst (mainly a chiral secondary amine such as proline) and substrate (mainly an aldehyde), followed by asymmetric formation of new bond between the a-carbon of carbonyl compound and electrophile. Detachment of organocatalyst provides optically active a-substituted carbonyl compound, and the free organocatalyst then participates in another catalytic cycle (Figure 6.1a) [2]. 

Norrish Type II reactivity is often a common reaction path for ketones with available Y 7< °sens. Hydrogen abstraction by the excited carbonyl group results in the formation of a 1,4-biradical which can undergo either bond cleavage to reform the carbonyl group and an alkene or bond formation to yield a cyclobutanol derivative. The fragmentation path is followed by the ketone (13). The interest in this reaction is the control which can be exercised on the ketonization of the resultant enol (14). Apparently in the presence of (->-ephedrine asymmetric formation of the final product, (R)-2-methylindanone (15),... 

Ketone (1) gives the enol (2) by a Norrish Type II reaction. In the presence of (-)-ephedrine, asymmetric formation of the final product (3) occurs by enantioselective transformation of the enol (Henin et al.). In the well known photo-cyclisation of o-alkyl substituted aryl ketones to cyclobutenols, it has now been shown that a dienol intermediate precedes the cyclobutenol this resolves a longstanding disagreement (Wagner et al.). In the ketones such as (4), a 1,5-biradical is... 

Introduction Formation of C-H and C-C Bonds Part I - Asymmetric Formation of C-H Bonds... 

Noyori s synthesis of menthol by Rh+-catalysed [1,3]H shifts Corey s CBS Reduction of Ketones A synthesis of the H1 blocker cetirizine Part II - Asymmetric Formation of C-C Bonds Organic Catalysis... 

---