Diaxial addition

The stereochemistry of formation and rearrangement of vicinal dihaUdes has been elucidated, chiefly by Barton s group. Trans diaxial addition occurs but the product may then equilibrate with the more stable... 

These reactions are examples of the preferred trans-diaxial opening of epoxides and the analogous trans-diaxial addition to double bonds. 

A wide variety of unsaturated carboxylic acids have been allowed to react with HBr.101 Carboxylic acids with remote C—C double bonds react as simple alkenes.138,139 4-Pentenoic acid reacts with HBr neat or in a polar solvent to give exclusively 4-bromopentanoic acid, but the reaction in nonpolar solvents affords only 5-bromopentanoic acid.136 On the other hand, 5-methyl-4-hexenoic acid produces only the S-bromo acid. A similar pattern is followed by 3-butenoic, 3-pentenoic and 4-methyl-3-pentenoic acids. No matter what the substitution pattern, 2-alkenoic acids always favor the 3-bromo acid.113,136,140,141 Addition of HBr to cyclic a,3-unsaturated acids initially forms predominantly the product of trans diaxial addition which upon longer reaction time or higher temperature isomerizes to the trans product (equation 92).57,141,142 Similar observations have been made on bicyclic a.fj-unsaturated acids.141... 

While the regiochemistry of simple electrophilic additions to double bonds is controlled by a combination of electronic (Maikovnikov rule), stereoelectronic (trans diaxial addition to cyclohexenes) and steric factors,9 the intramolecular nature of electrophilic heteroatom cyclizations introduces additional conformational, stereoelectronic and entropic factors. The combination of these factors in cyclofunctionalization reactions results in a general preference for exo cyclization over endo cyclization (Scheme 4).310 However, endo closure may predominate in cases where electronic or ring strain factors strongly favor that mode of cyclization. The observed regiochemistry may differ under conditions of kinetic control from that observed under conditions of thermodynamic control. 

The polarized-TT frontier molecular orbital (PPFMO) method has been employed to study protonation and sulphenylation of sugar-related dihydrofurans and tetrahydropy-rans. The predictions are consonant with the experimental observations62. Contrary to expectations, the proton-catalysed addition of alcohols to glycals, such as 30, has been shown by isotope labelling (2H) not to be anii-diaxial addition. This observation has been rationalized by the initial attack by deuteron from the bottom, giving ion 31, and by the anomeric effect favouring axial substituent at C-l (32)63. 

Conflict between electronic (Markovnikov) and conformational control in the electrophilic additions of alkenes is well known in steroids and generally leads to the conformationally preferred diaxial addition product. Methoxybrominations of 2-methyl-5a-cholest-2-ene (69) and its 3-methyl isomer (71) illustrate control by a combination of conformational and electronic factors the products indicate that the first-formed bromonium ion equilibrates between the 2a,3a and the 2/3,3/3 configurations before suffering nucleophilic attack by methanol. The major product (72) from the 3-methyl compound results from methanolysis of the less stable 2/8,3/3-bromonium ion, axial attack at the tertiary C-3 being the most favourable mode of reaction.95... 

This stereochemical character is shared by all addition reactions involving a halonium ion, so that mixed halogens e.g. Br-F [8g], Br Cl [go], I Cl [gi] and I F [g2]), and also reagents like hypobromous acid (Br-OH) [gs], acetyl hypobromite (CH3CO OBr) [g4] and iodine isocyanate (I NCO) [gs] lead to diaxial addition products, with the... 

Whereas hydrolysis of epoxides leads to the trans diaxial addition of water and the formation of trans glycols (1,2-diols), cis glycol formation involves the addition of osmium(VIII) oxide (osmium tetroxide, OsO ) or cold dilute aqueous potassium manganate(Vll) (potassium permanganate) to an alkene. 

Addition of bromine to cyclohexene is subject to stereoelectronic control and proceeds via formation of a bromonium ion intermediate. This is followed by spontaneous antiperiplanar (8 2 type), antiparallel opening by the bromide anion via a chairlike TS. Thus, under kinetic control, the predominant or exclusive product formed is via path b resulting from diaxial addition of Br2 to the double bond. 

The reagent (or its equivalent) can be generated by addition of N-bromouceltimide to an acetic acid solution of lithium acetate and an oleflnic substrate such us (I) irans-diaxial addition gives the bromohydrin acetate (2) in 74% yield. Reaction conditions are essentially neutral, acid-sensitive groups are not attacked, and the... 

To install the appropriate functionality at C2, solution phase chemistry has relied on a trans-diaxial addition of an iodonium electrophile in the presence of an amine to form an iodosulfonamide. Displacement of iodine proceeds presumably through an aziridine intermediate and may be induced by a thiolate nucleophile to fashion thioethyl 2-amidoglycosyl donors [38]. Successful transfer of this method to the solid support allowed polymer-bound glycals to be converted into thioethyl gly-cosyl donors. These donors were in turn coupled with a variety of glycosyl acceptors, including glycals [39]. 

Selenenylation is a stereospecific anti addition with acyclic alkenes.Cyclohexenes undergo preferential diaxial addition. 

Oxymercuration of unhindered alkenes is usually a stereospecific anti addition. This result is consistent with the involvement of a mercurinium ion intermediate that is opened by nucleophilic attack. Conformationally biased cyclic alkenes such as 4-f-butylcyclohexene and 4-f-butyl-l-methycyclohexene give exclusively the product of anfi-diaxial addition. ... 

The proton-catalyzed addition of alcohols to glycals is shown not to be trans diaxial addition. Bollitt et al. [83] reported that triphenylphosphine hydrobromide (TPP-HBr) was the catalyst of choice for mild and high-yield protonation and subsequent glycosidation of glycals (Fig. 5.44). 

In cyclic olefins, addition occurs by diaxial addition ... 

Addition of iodine azide to the D-glucal derivatives (39) gave mostly 2-deoxy-2-iodo-glycosyl azides (40) derived from trans-diaxial addition to the double bond. D-galactal and D-xylal derivatives... 

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