Subject stereoselective synthesis

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

Tor a treatise on this subject, sec Morrison Asymmetric Synthesis, 5 vols. [vol. 4 co-cditcd by Scott] Academic Press New York, 1983-1985. For books, see N6gr4di Stereoselective Synthesis VCH New York, 1986 Eliel Olsuka Asymmetric Reactions and Processes in Chemistry American Chemical Society Washington, 1982 Morrison Mosher Asymmetric Organic Reactions Prentice-Hall Englewood Cliffs, NJ, 1971, paperback reprint, American Chemical Society Washington, 1976 Izumi Tai, Ref. I. For reviews, see Ward Chem. Soc. Rev. 1990, 19, 1-19 Whitesell Chem. Rev. 1989, 89, 1581-1590 Fujita Nagao Adv. Heterocycl. Chem. 1989, 45, 1-36 Kochetkov Belikov Russ. Chem. Rev. 1987, 56, 1045-1067 Oppolzer Tetrahedron 1987, 43, 1969-2004 Seebach Imwinkelried Weber Mod. Synth. Methods 1986, 4, 125-259 ApSimon Collier Tetrahedron 1986, 42, 5157-5254 Mukaiyama Asami Top. Curr. Chem. 1985, 127, 133-167 Martens Top. Curr. Chem. 1984, 125, 165-246 Duhamel Duhamel Launay Plaqucvcnt Bull. Soc.Chim. Fr. 1984,11-421-11-430 Mosher Morrison Science 1983,221, 1013-1019 Schollkopf Top. Curr. Chem. 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

In this chapter, key studies which have led to the current understanding of the mechanism of this transformation will be discussed, as a basis for dealing with issues of selectivity and choice of experimental variables in subsequent sections. Since the initial development of this reaction, it has evolved in scope to become a primary method for the stereoselective synthesis of epoxides to which an electronegative substituent is directly attached. Several recent variations on the initial protocol which afford functionally diverse molecules are the subject of Section 1.13.3. Section 1.13.5 examines related reactions that afford substituted aziridines instead of epoxides, and Section 1.13.6 examines some recent variants of the re-... 

Oxabicyclo[3.2.1]oct-6-en-2-ones are also available from this chemistry, as illustrated in Scheme 30. Treatment of 84 with sodium methoxide and then lithium hydroxide, followed by subjecting the resulting acid to the standard Curtius rearrangement conditions, results in the formation of 8-oxabicyclo[3.2.1]oct-6-en-2-one (85) in 52% yield. Racemic 85 has been used by Vogel in a stereoselective synthesis of the P-C-hexopyranoside 86. ... 

An efficient stereoselective synthesis of (-l-)-241D (13) using reductivea-mination was reported by Rao and coworkers [22]. Decanal (70) was subjected to an enantioselective Maruoka allylation using titanium complex of (S,S)-BINOL and furnished 71 with 98% ee. Tosylation of the hydroxyl group of 71 followed by azidation gave 72. The azide 72 was reduced to amine followed by protection with CbzCl to give 73. Sharpless AD of 73 with AD mix... 

In addition to alkenes, imines are tremendously popular aziridine precursors via an aza-Darzens approach. For example, a stereoselective synthesis of C-sulfonylated aziridines was reported via an aza-Darzens approach employing bromomethyl phenyl sulfbne, NaHMDS, and a series of N-tert-butanesulfinyl imines (14MI969). Likewise as shown below, chiral tert-butane- and mesitylsulfinimines were subjected to an aza-Darzens reaction with substituted 2-bromoesters to provide a host of aziridines in good yield with excellent stereocontrol (14OL6920). In turn, these aziridines could be subsequently converted to chiral A/-H aziridines in a total of three steps starting with a wide range of commercially available aldehydes. 

The versatihty of the present furanone synthetic method was demonstrated in the stereoselective synthesis of the Z-isomer of multicolanate (139) [118] (Scheme 26). The prerequisite compound 137 was prepared by successive treatment of appropriate organomagnesium and organohthium reagents, and it was transformed smoothly with lead tetraacetate to the target molecule (the incomplete acetate product 138 was subjected to elimination reaction with DBU). 

The dramatic requirement for the specifically placed benzylidene has been subjected to elegant analysis by Bols [75], who noted that the stereoselective synthesis employs, as its key element, donors that have been disarmed by locking their conformation. .. The purpose of the lock, Bols contends, is to provide an antiperiplanar relationship between the 06-C6 and C5-05 bonds, an arrangement that facilitates electron withdrawal that stabilizes the oxocarbenium ion intermediate. 

A highly stereoselective synthesis of cis- and trans-3,5 1isubstituted pyrazolidines has been developed in which the presence or absence of an N-1 protecting group controls product stereochemistry [42]. For example, treatment of 39 with 4-bromobiphenyl and a palladium catalyst in the presence of NaOtBu affords the trans-disubstituted product 41 (Eq. (1.18)), whereas subjection of 40 to similar reaction conditions affords the cis-disubstituted product 42 (Eq. (1.19)). 

Starting materials, like 141, which are accessible from alkenes by azido-selenenylation, afforded only in a few cases vinyl azides exclusively as shown by the example 141 142 (Scheme 5.19). In most cases, after oxidation of the vicinal phenylseleno azides and elimination reaction on the intermediate selenoxide, mixtures of allyl and vinyl azides were obtained. Ring opening of trialkylsilyl-substituted epoxides was utilized several times for stereoselective synthesis of vinyl azides. Thus, treatment of the frani -contigured oxiranes 143 with azidotrimethylsilane and boron trifluoride etherate yielded cis-conflgured products 145. This result was explained by the intermediate 144 which should undergo anti-elimination. On the other hand, when subjected to sodium azide in dimethylformamide, epoxides 146 were transformed into vinyl azides 148 via... 

With the conformational analysis in mind, our investigation commenced with the stereoselective formation of 2,3-trani-2,6-tran5-tetrahydropyrans. To determine the feasibility of the oxa-conjugate addition reaction for the stereoselective synthesis of 2,3-frans-2,6-trans-tetrahydropyrans, allyl alcohol (Z)-2.38a was prepared by dithiane coupling of (Z)-2.36 with (5)-glycidyl benzyl ether (2.37a) and subsequently subjected it to the tandem oxidation/oxa-conjugate addition reaction... 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

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