Alkoxy tertiary

Reaction with carbonyl electrophiles is possible, so enantiopure stannanes are excellent precursors of enantiopure a-alkoxy tertiary alcohols [165,167], a-alkoxy acids and esters [180], and a-alkoxyketones [181], and y-alkoxyhydrazides (precur-... 

Under moderate conditions, primary alkoxy radicals tend to undergo reaction 12 whereas secondary and tertiary alkoxys tend to undergo -scission. In general, the alkyl group that can form the lowest energy radical tends to become the departing radical. The -scission of secondary alkoxy radicals yields aldehydes as the nonradical products tertiary alkoxy radicals yield ketones. 

An asymmetric synthesis has used the reduction of imonium salts to optically active tertiary amines with lithium aluminum alkoxy hydrides derived from optically active alcohols (538,539). 

It will be observed that most syntheses yield pyrylium salts in which positions 2,4, and 6 are substituted. Since according to formulas Ib-lc these positions have a partial positive charge, it can readily be understood why electron-donating substituents (hydroxy, alkoxy, alkyl, or aryl) in these positions stabilize the pyrylium salts. Only three pyrylium salts which do not have substituents in either a-position have been reported and few unsubstituted in y or in one a-position they are less stable toward hydrolysis, and in the case of perchlorates they explode more easily, than 2,4,6-trisubstituted compounds. In fact, the former are secondary, the latter tertiary carbonium ions. This fact also explains why the parent compound (1) was prepared only in 1953. 

Acid-catalyzed solvolysis of hydroxylactams to (m)ethoxylactams has already been discussed. Secondary or tertiary alcohols can also be used, though in the latter case yields are lower. The reverse reaction, viz. hydrolysis of the alkoxy compounds, is generally performed in aqueous acid. 

However, the situation is not as clear-cut as it might at first seem since a variety of other factors may also contribute to the above-mentioned trend. Abuin et a/.141 pointed out that the transition state for addition is sterically more demanding than that for hydrogen-atom abstraction. Within a given series (alkyl or alkoxy), the more nucleophilic radicals are generally the more bulky (i.e. steric factors favor the same trends). It can also be seen from Tabic 1.6 that, for alkyl radicals, the values of D decrease in the series primary>secondary>tertiary (i.e. relative bond strengths favor the same trend). 

A novel approach was developed very recently by Kita et al. [15]. DKR of allylic alcohols was performed by combining a lipase-catalyzed acylation with a racemization through the formation of allyl vanadate intermediates. Excellent yields and enantioselectivities were obtained. An example is shown in Figure 4.4. A limitation with this approach for the substrates shown in Figure 4.4 is that the allylic alcohol must be equally disubstituted in the allylic position (R = R ) since C—C single bond rotation is required in the tertiary alkoxy intermediate. Alternatively, R or R can be H if the two allylic alcohols formed by migration of the hydroxyl group are enantiomers (e.g. cyclic allylic acetates). 

Introduction of an additional substituent such as alkyl, alkoxy, halogen, etc. at 3 -position has a large effect on color. That is, green color changes to red color when there is a tertiary amino group at 2 -position. Thus, 2 -dibenzylamino-6 -diethylamino-3 -methylfluoran (47 R1 = H, R2 = CH3 ),40 2 -dibenzylamino-6 -diethylamino-3 -ethylfluoran (47 R1 = H, R2 = C2H 5),34 3 -chloro-2 -dibenzylamino-6 -diethylaminofluoran (47 R1 = H, R2 = Cl),34 6 -((V-ethyl-4-methylanilino)-3 -methyl-2 -((V-methylanilino)flu-... 

Along with tertiary hydroperoxide of ether, the BDE of the O—H bonds of alkoxy hydroperoxides are higher than that of similar hydrocarbons. Very valuable data were obtained in experiments on ether oxidation (RiH) in the presence of hydroperoxide (RiOOH). Peroxyl radicals of oxidized ether exchange very rapidly to peroxyl radicals of added hydroperoxide ROOH and only R02 reacts with ether (see Chapter 5). The rate constants of alkylperoxyl radicals with several ethers are presented in Table 7.18. The reactivity of ethers in reactions with peroxyl radicals will be analyzed in next section. 

The preference for the /3-silyl isomer product complements methods available for hydrostannation of alkynes, for which the a-stannyl regioisomer is formed preferentially.70 7011 70c In addition, the /3-silyl products serve as the platform for a tertiary alcohol synthesis (Scheme 15). Upon treatment of vinylsilanes such as B with tetrabutylam-monium fluoride (TBAF) in DMF at 0 °C, a 1,2 carbon-to-silicon migration occurs, affording the tertiary heterosilane E. Oxidation of the C-Si bond then provides the tertiary alcohol. Good 1,2-diastereocontrol has been demonstrated for y-alkoxy substrates, as in the example shown. The studies suggest that the oxidation of the sterically demanding silane intermediate is facilitated by the intramolecular formation of a silyl hemiketal or silyllactone for ketone or ester substrates, respectively.71... 

V-alkoxycarbonylamino add (Figure 1.10, path B) did not occur without immediate expulsion of the alkyl group, giving the amino-acid Af-carboxyanhydride (see Section 7.13). 2-Alkoxy-5(47/)-oxazolones are now recognized as intermediates in coupling reactions and are products that are generated by the action of tertiary amines on activated A-alkoxy carbonyl amino adds (see Section 4.16).20 22... 

More /V-acylurea is generated if tertiary amine is present because the latter removes any protons that might prevent the rearrangement (see Section 2.12). The two intramolecular reactions also occur to a greater extent when interaction between the O-acylisourea and the /V-nucleophile is impeded by the side chain of the activated residue. This means that more 2-alkoxy-5(4//)-oxazolone and /V-acylurea are generated when the activated residues are hindered (see Section 1.4). A corollary of the above is that the best way to prepare an /V-acylurea, should it be needed, is to heat... 

That being said, it must be recognized that the evidence that the (V-acy I isourea is the precursor of the 2-alkoxy-5(4//)-oxazolone is only circumstantial because experiments starting from the former have yet to be achieved. The oxazolone could theoretically come from the symmetrical anhydride. The latter generates 2-alkoxy-5(4//)-oxazolone in the presence of tertiary amines (see Section 4.16) even dicy-clohexylcarbodiimide (DCC) was basic enough to generate 2-t< rt-butoxy-5(4 )-oxazolone from Boc-valine anhydride. However the weight of evidence points to O-acylisourea as the precursor of the 2-alkoxy-5(4//)-oxazolone. In the absence of. V-nucleophile, such as in the preparation of esters, the major precursor of product is the symmetrical anhydride.7,8... 

FIGURE 2.14 Peptide-bond formation from chlorides of A-alkoxycarbonylamino acids. N-9-Fluorenylmethoxycarbonylamino-acid chlorides.41 The base is NaHCO, Na2C03, or a tertiary amine. The reaction is carried out in a one- or two-phase system. The latter is used to try to suppress formation of the 2-alkoxy-5(4//)-oxazolone that is generated by the action of the base on the acid chloride. The method is applicable primarily to Fmoc-amino-acid derivatives that do not have acid-sensitive protecting groups on their side chains. 

FIGURE 4.14 Reactions of activated A-alkoxycarbonylamino acids in the presence of tertiary amine. Acyl halides and mixed and symmetrical anhydrides generate 2-alkoxy-5(4/7)-oxazolone in the presence of tertiary amine. Aminolysis of 2-alkoxy-5(47f)-oxazolone in the presence of E N led to partially epimerized products. OAct = activating group. 

With the exception of adamantane and few related compounds [1-5] in which dichlorocarbene reacts at the tertiary C-H centre, the yields for the majority of insertion reactions into hydrocarbons are low and of little synthetic value (Table 7.1). Reaction also occurs in low yield at benzylic C-H sites [1, 6, 7] and, in the case of simple alkanes, the insertion reaction is promoted by alkoxy groups [1,6-14], Thus, whereas methylcyclohexane produces only 4% yield of the l-dichloromethyl-l-methylcyclohexane, the corresponding yield with 1-methoxycyclohexane is 13% [6], Similarly, the low yielding reaction of 1-methoxyadamantane with dichlorocarbene produces l-dichloromethyl-3-methoxyadamantane by insertion into the tertiary C-H site and (2,2-dichioroethoxy)adamantane by reaction at the primary C-H site, which is activated by the methoxy group. No reaction occurs at the secondary C-H sites [2],... 

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