Rotamers reactivity

The cycloaddition of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to tricar-bonylchromium complexed styrenes proceeds with high stereoselectivity (Scheme 1.17), thus offering a new synthetic route to optically active 3,5-di-substituted 4,5-dihydroisoxazoles (213). The preferred formation of cycloadducts 44 rather than 45 shows that nitrile oxide attacks the it face opposite to Cr(CO)3 and the reactive rotamer of the dipolarophile is transoid (213). 

In virtually all other W(CHR)(NAr)(OR )2 complexes only the syn alkylidene ro-tamer is observed readily [63]. It was not clear at the time why rotamers could be observed in this particular case and why they interconverted readily. Later it was shown that the reactivities of certain syn and anti species could differ by many orders of magnitude and that the rates of their interconversion also could differ by many orders of magnitude as OR was changed from O-t-Bu to OC-Me(CF3)2. Therefore in any system of this general type two different alkylidene rotamers could be accessible (although both may not be observable), either by rotation about the M=C bond, or as a consequence of the metathesis reaction itself. The presence of syn and anti rotamers further complicates the metathesis reaction at a molecular level, and at least in ROMP reactions (see below) in important ways. The apparent ease of interconversion of syn and anti rotamers in phenoxide complexes could be an important feature of systems in which access to both syn and anti rotamers must be assured (see later). 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

The application of this methodology to suitably functionalized alkynes has allowed a direct and easy synthesis of important heterocyclic compounds starting from readily available substrates. New /1-lactone [100,101] and /3-lactam [102] derivatives were synthesized in good yields from a,a-disubstituted propynyl alcohols and amines, respectively (Eq. 38), through the mechanistic route shown in Scheme 18, path a. The substitution a to the triple bond was a necessary requisite for cychzation to occur, owing to the reactive rotamer effect [301]. 

The foregoing examples of differential reactivities of rotamers may be summarized by saying that the reactivity is controlled by the steric factor. The difference in the reactivities of rotamers of 9-(2-bromomethyl-6-methyl-phenyl)fluorene (56) in SN2 type reactions falls in the same category (176). However, the substituent effect is not limited to a steric one there can be conformation-dependent electronic effects of substituents as well. A pertinent example is found in the reactivity of the bromomethyl compound (56) when the rotamers are heated in a trifluoroacetic acid solution (Scheme 10). The ap form gives rise to a cyclized product, whereas the sp form remains intact (176). The former must be reacting by participation of the it system of the fluorene ring. 

In conclusion, the chemistry of atropisomers holds a promising future in providing reactivity data for rotamers and information on molecular interactions that are otherwise not detectable. It is especially promising in that a variety of functional groups can be introduced into the 9-arylfluorene and 9-substituted triptycene systems and thus the electronic as well as steric effects of substituents can be examined. In the past, steric effects on reactivity were almost die sole... 

The functionalization of folded motifs is based on an understanding of secondary and tertiary structures (Fig. 2) and must take into account the relative positions of the residues, their rotamer populations and possible interactions with residues that do not form part of the site. For example, glutamic acid in position i has a strong propensity for salt-bridge formation, and thus reduced reactivity, if there is a Lys residue available i-4 in the sequence, but the probabihty is much less if the base is i-3 [60]. Fortunately, there is a wealth of structural information on the structural properties of the common amino acids from studies of natural proteins that provides considerable support for the design of new proteins. The naturally occurring amino acids have so far been used to construct reactive sites for catalysis [11-13], metal- and heme-binding sites [14,15,19,21,22] and for the site-selective functionalization of folded proteins [24,25]. 

A facilitated transition hypothesis has been suggested to replace the reactive rotamer hypothesis as an explanation for the gem-dialky I effect in intramolecular cyclization reactions.59... 

The reaction of 219 with 7 (R = Me) proceeds mainly via the less abundant but much more reactive anti rotamer of the initiating and propagating species. The first four propagating species may be distiguished in the H NMR spectrum for the longer chains the anti and syn rotamers are just resolved, in the ratio of 1 6. The corresponding 13C... 

The structure of diphosphallenic radical cations, generated from the allene ArP=C=PAr by electrochemical oxidation, has been examined using EPR spectroscopy. Ab initio calculations including correlation effects at the MP2 and MCSCF levels have determined that two rotamers exist compatible with Jahn-Teller distortion of the allene.146 Anodically generated radical cations of alkyl phosphites [(RO P] and silylphosphites [(RO)2POSiMe3] reacted with alkenes by initial attack at the C=C bond followed by electron transfer, deprotonation, and elimination of an alkyl or trimethylsilyl cation to form identical alkyl phosphate adducts.147 The electron ionization-induced McLafferty rearrangement of n-hexylphosphine afford the a-distonic radical cation CTEPH, the distinct reactivity of which suggests there is no... 

Conformationally rigid s-glycosides were found to be reactive towards ozone. At least one of the rotamers E], Eg, and Eg of a B-glycoside (Fig. 9) which corresponds to conformers A, jl, and C respectively of an acetal function should therefore be reactive. Compounds 57 and 158 are rigid model compounds for rotamers E- and g. These two compounds react with ozone thus, conformers A and are reactive conformers. On the other hand, the unreac-tive compound 159 is a rigid model for rotamer Eg thus, conformer B is not reactive, as predicted. 

Jung, M. E. Gervay, J. gem-Dialkyl effect in the intramolecular Diels-Alder reaction of 2-fur-furyl methyl fumarates the reactive rotamer effect, enthalpic basis for acceleration, and evi-... 

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