Functionalization remote

Thilgen C., Cardullo F., Haldimann R., Isaacs L., Seiler P., Diederich F., Boudon C., Gisselbrecht J. P., Gross M. Synthesis of Multiple Adducts of C60 With Specific Addition Patterns by Simple and Reversible (Templated) Tether-Directed Remote Functionalization Proc. - Electrochem. Soc. 1996 96-10 1260-1271 Keywords fullerene C60, regiochemistry... 

Ring-Chain Tautomerism of Bis-N,N-Oxyiminium Cations Scheme 3.215 shows the ring-chain tautomerism of selected bis-7V,7V-oxyiminium cations, which was suggested as an explanation of the reactivity of y-functionalized AN. This problem is not only of theoretical interest but also of importance for the development of a simple and efficient procedure for the synthesis of conjugated enoximes (395) containing a remote functional group (153, 293) (Scheme 3.218). 

An increase in the size of the carbocycle and steric hindrance of the base leads to a decrease in the contribution of the target enoxime in the reaction products. Hence, in each particular case it is necessary to perform special experiments to elucidate whether the scheme is applicable for the synthesis of conjugated enoximes containing a remote functional group and to find optimal conditions. 

Allylic alcohol derivatives are quite useful in organic synthesis, so the asymmetric synthesis of such compounds via asymmetric hydrogenation of dienyl (especially enynyl) esters is desirable. The olefin functionality preserves diverse synthetic potential by either direct or remote functionalization. Boaz33 reported that enynyl ester and dienyl ester were preferred substrates for asymmetric hydrogenation using Rh-(Me-DuPhos) catalyst [Rh(I)-(R,R)-14], and products with extremely high enantioselectivity (>97%) were obtained (Schemes 6-11 and 6-12). 

L. Isaacs, R. E Haldimann, F. Diederich, Tether-directed Remote Functionalization of Buckminsterfullerene Regiospecific Hexaadduct Formation , Angew. Chem. Int. Ed. Engl. 1994,33, 2339-2342. 

L. Isaacs, E Diederich, R. F. Haldimann, Multiple Adducts of C6o by Tether-Directed Remote Functionalization and Synthesis of Soluble Derivatives of New Carbon Allotropes Cn(60+5) , Helv. Chim Acta 1997, 80, 317-342. 

Apart from glycosyl acetate and benzoate donors, more elaborate O-carbonyl derivatives offer potential for distinct modes of anomeric leaving group activation. Many of these donors (Scheme 3.21) involve activation of an anomeric O-carbonyl derivative 134 at a remote functional group (Y). The adivated remote functionality, in turn,... 

Glycosyl esters with remote functionality constitute a relatively new class of O-carbonyl glycosyl donors, which fulfill the prospect of mild and chemoselective activation protocols (Scheme 3.22). For example, Kobayashi and coworkers have developed a 2-pyridine carboxylate glycosyl donor 134 (Y = 2-pyridyl), which is activated by the coordination of metal Lewis acid (El+) to the Lewis basic pyridine nitrogen atom and ester carbonyl oxygen atom [324]. In the event, 2-pyridyl (carbonyl) donor 134 and the monosaccharide acceptor were treated with copper(II) triflate (2.2 equiv) in diethyl ether at —50 °C, providing the disaccharide 136 in 70% (a P,... 

In less repetitive syntheses, it is possible to use remote functional groups as "control elements", a technique which depends more upon the opportunist tactics developed in the course of a synthesis rather than of a premeditated strategy. Such is the case, for instance, of the synthesis of strychnine (i) by Woodward [2], in which after synthesising the intermediate 2 a hydrogen at C(8) must be introduced onto the P-face (4), i.e., onto the most hindered concave face of the molecule (Scheme 8.1). Usually the reduction with a metal hydride would lead to the a-C(8)-H isomer (i.e., the hydride ion will atack from the less hindered face of the molecule), however in the present case the P-OH group at C(21) acts as a control element and, besides the reduction of the amide at C(20), a hydride ion attacks at C(8) from the P-face by an intramolecular transfer of the complex C(21)-0-Al-H (3). 

McNaughton, B. R. Bucholtz, K. M. Camaano-Moure, A. Miller, B. L. Self-selection in olefin cross metathesis The effect of remote functionality. Org. Lett. 2005, 7, 733-736. 

Nonstabiiized lithiooxiranes can be prepared by the reaction of strong bases such as alkylithium reagents or lithium amides. However, as already discussed in a preceding section (Section II), the competition between a- and /3-deprotonation has to be adressed, and the issue of this competition is highly dependent on the structure of the starting oxirane as well as on the nature of the base used. These lithiooxiranes are very reactive species. In order to prevent their decomposition, they can be stabilized by a diamine ligand. Further stabilization can be obtained by a remote functionality. 

The lithiooxirane can also be stabilized by a remote functionality in the molecule. The deprotonation of the two isomeric terminal oxiranes 113 and 114 (Scheme 53) affords the two remote carbonyl stabilized lithiooxiranes 115 and 116 which, due to this stabilization, could be trapped by various electrophiles. Deprotonation occurs stereoselectively cis to the ester moiety. The reaction with aldehydes gives the corresponding epoxylactones in good yields and excellent stereoselectivities . 

In 1994, Diederich and co-workers reported a very important approach for the regioselective formation of multiple adducts of Cjq by tether-directed remote functionalization [75]. This technique allows for the synthesis offullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered addends. This important subject has been extensively reviewed [26, 76, 77]. 

The first example of a tether remote functionalization was the synthesis of the tris-64 (Scheme 10.14) [75,78]. For this purpose the computer-aided chemically designed addend 63 was allowed to undergo a successive nucleophilic cyclopropanation/ [4-1-2] cycloaddition sequence yielding the tris-adduct 64 in 60% yield with complete regio selectivity. Subsequent cyclopropanation of the remaining octahedral sites with a large excess of diethyl bromomalonate and DBU afforded the hexakisadduct 65... 

Scheme 10.16 Tether-directed remote functionalization leading to the tetraethynylated [2 4] hexakisadduct 76. (i) O2, hv, PhCI (ii) PPhj, PhCI ...

In 1975 Brown and Yamashita reported that a triple bond in any position of a straight chain hydrocarbon or acetylenic alcohol, when treated with a sufficiently strong base, could be isomerized exclusively to the free terminus of the chain. The "zipper reaction" thus provides a general solution to the problem of remote functionalization of a long hydrocarbon chain. Isomer-izations along chains of thirty carbon atoms have been achieved. 

Substitutions at saturated carbon atoms that are subject to control by remote functionalities may be best illustrated by the ring opening of aziridines [35] and epoxides [36, 37]. 

Remote function control of the regiochemistry for 1,2-addition in the bridged bicycloalkene systems [114] has been delineated. Again, the polarity alternation rule proves very useful for rationalizing these results. 

Burke et al. [84] synthetised nagilactone F (55) by a polyenic cyclization initiated with acetal and concluded with vinylsilane, giving an overall yield of 6%. The key steps in this synthesis were the coupling of substrates 166 and 167 with control of the absolute and relative stereochemistry, the cationic biscyclization to form the intermediate tricyclic trans-anti-trans 169 and the formation of the D ring by regio-selective intramolecular remote functionalization. 

The magnesium-ene reaction provides a unique approach to remote functional groups. ... 

This reaction is generally part of a sequence followed by Claisen rearrangement to generate a remote functional group (aldehyde). 

Since enolates also add via a ligand attack process, the regioselectivity that they exhibit is quite comparable to soft caibon nucleophiles. Alkyl or aiyl substituents at the allyl termini direct attack to the less substituted terminus (equations 228-232) functional groups such as COaMe and halogen at one allyl terminus direct attack to the remote terminus (equations 233 and 234). Remote functionalities such as —OR also direct addition to the allyl terminus more removed from the substituent (equations 23S and 236). 

The Hofmann-Loffler-Freytag (HLF) reaction is the oldest known reaction that involves aminium cation radicals (Scheme 14) (50JA2118 60JA1657). This reaction is a remote functionalization reaction where an N-chloro- or N-bromo-amine 46 is converted to a 8-haloamine 49 via the intermediate aminium cation radical 47. Pyrrolidine products are obtained by cyclization of the 8-haloamines under basic conditions. A comprehensive survey of the synthetic utility of this reaction has been reported by Wolff (63CRV55). 

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