Y position

Similai selectivity is observed in the synthesis of allylsilanes where X = CF3SO3 and Y = Si(CH3) 3 (304). Alkenyl- and alkynylborates containing a leaving group in the y-position rearrange to aUyhc and aUenic boranes, respectively (305). 

These examples show that silane reacts selectively with the y-position of aHyl compounds. However, ia its reaction with aHyl amine, a side reaction ia which silane biads to the -position takes place (40). 

Halogen Substituents. Halogen functional groups are readily replaced by nucleophiles, eg, hydroxide ion, especially when they ate attached at the a- or y-position of the pyridine ting. This reaction has been exploited in the synthesis of the insecticide chlorpyrifos [2921-88-2J (43) (42), and the insecticide tiiclopyi [55335-06-3] (44) (14,43). 2,3,5,6-Tetiachloiopyiidine [2402-79-1] reacts with caustic to form the hydioxylated material [6515-38-4], which then can be used to form (44) and (43). 

Work in the mid-1970s demonstrated that the vitamin K-dependent step in prothrombin synthesis was the conversion of glutamyl residues to y-carboxyglutamyl residues. Subsequent studies more cleady defined the role of vitamin K in this conversion and have led to the current theory that the vitamin K-dependent carboxylation reaction is essentially a two-step process which first involves generation of a carbanion at the y-position of the glutamyl (Gla) residue. This event is coupled with the epoxidation of the reduced form of vitamin K and in a subsequent step, the carbanion is carboxylated (77—80). Studies have provided thermochemical confirmation for the mechanism of vitamin K and have shown the oxidation of vitamin KH2 (15) can produce a base of sufficient strength to deprotonate the y-position of the glutamate (81—83). 

Pyridazines with a hydroxy group at an a- or y-position to a ring nitrogen atom, i.e. 3-and 4-hydroxypyridazines (4) and (5), exist predominantly in the oxo form. This conclusion is based on spectroscopic evidence from UV spectra of unsubstituted compounds and their A-methyl and O-methyl derivatives in alkaline, neutral and acidic solutions. In some instances, as for example for 6-oxo-l,6-dihydropyridazine-3-carboxamide, there is also evidence from X-ray analysis <54AX199, 63AX318). Maleic hydrazide and substituted maleic hydrazides exist in the monohydroxymonooxo form (6). 

Mannich reaction with pyridazinone 1-oxides takes place at the a- or y-positions relative to the iV-oxide group, in contrast to the reaction in the pyridazinone series, where N-substituted products are formed. Pyridazin-3(2FT)-one 1-oxide gives first the corresponding 6-substituted derivative with excess of the reagents, 4,6-disubstituted products are obtained. When position 6 is blocked the corresponding 4-dialkylaminomethyl derivatives are obtained. 

Treatment of pyridazine 1-oxides with phosphorus oxychloride results in a-chlorination with respect to the N-oxide group, with simultaneous deoxygenation. When the a-position is blocked, substitution occurs at the y-position. 3-Methoxypyridazine 1-oxide, for example, is converted into 6-chloro-3-methoxypyridazine and 3,6-dimethylpyridazine 1-oxide into 4-chloro-3,6-dimethylpyridazine. 

The analogy between a substituent linked to a carbonyl group and a substituent in an a or, to a lesser extent, a y-position to a pyridinic nitrogen has been discussed in Section 4.02.3.1.2). The conclusions hold for pyrazoles and indazoles. 

The 8 Hz coupling indicates a proton in the y-position (B) the 5 Hz coupling locates a vicinal proton in position a (C), the additional 0.9 Hz coupling locates the remaining proton in position a (D) and thereby the p-position of the substituent. 

When the combination X,Yor X, Y is of the capto-dative type, as is the case for an alkoxy and an ester group, the enthalpy of bond dissociation is 10-15 kcal lower than when all four groups are electron-attracting. When the capto-dative combination CN/NR2 occupies both the X, Y and the X, Y positions, the enthalpy for dissociation of the C(3)—C(4) bond is less than lOkcal/mol. ... 

Ketones in which the double bond is located in the p,y position are likely candidates for a-cleavage because of the stability of the allyl radical that is formed. This is an important process on direct irradiation. Products then arise by recombination of the radicals or by recombination after decarbonylation. 

Constitution. On oxidation with chromic acid, conhydrine yields Z-piperidyl-2-earboxylic acid. It is converted into Z-coniine either by reduction of the iodo-derivative (iodoconiine), C,HijNI, formed by the action of hydriodic acid and phosphorus at 180° or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene. These and other observations indicate that the p- ygen atom must occur as a hydroxyl group, in the w-propyl side-chain in either the a- (XV) or (XVI) position, since the y-position would involve... 

HS(CH2) SH, BF3-Et20, CH2CI2, 25°, 12 h, high yield, n = 2, n = 3." In a,)8-unsaturated ketones, the double bond does not migrate to the p,y-position, as occurs when an ethylene ketal is prepared. Aldehydes are... 

Ironically, auxiliary-induced control via the alkene failed to generate synthetically useful selectivities, but direct substrate-induced control did. In particular, chiral silyl enol ethers with stereocenters in the y-position allowed the synthesis of enantiomerically... 

The Boekelheide reaction and related reactions involves treating pyridine N Oxides 1 with acylating agents to afford rearranged products 2. Traditionally, the rearrangement occurs at the a-position but variations andyor side-products of this reaction afford y-position modification. 

Less reactive electrophilic reagents like those involved in acylation or alkylation apparently do not react with phenyl-substituted pyrylium salts the p-acylation of a phenyl group in position 3 of the pyrylium salt obtained on diacylation of allylbenzene (Section II, I), 3, a), and the p-l-butylation of phenyl groups in y-positions of pyrylium salts prepared by dehydrogenation of 1,5-diones by means of butyl cations (Section II, B, 2, f) probably occur in stages preceding the pyrylium ring closure. 

A convenient method leading to pyrans (38) consists in the nucleophilic addition of R anions to 2,6-disubstituted pyrjdium salts, in which the y-position (secondary carbonium ion) is more reactive than the a-positions (tertiary carbonium ions), in opposition to the reactivity of 2,4,6-trisubstituted pyrylium salts.Krohnke and Dickore as well as Dimroth and WolH showed that 2,6-diphenyl-pyrylium salts add the anions R of nitromethane, 1,3-diketones, malonodinitrile, ethyl cyanoacetate, and benzoylacetonitrile. Similar reactions are known in the flavylium series. -Nonactivated R ... 

The jS-position of pyridine 1-oxide is much less reactive than either the a- or y-position. This is shown for the displacement of the chloro group in structures 39 and 40 the relative rates are indicated (jS = 1) at... 

There are conflicting generalizations in the heterocyclic literature as to the relative reactivity of a- and y-positions in azines toward nucleophiles. Variations in the relative reactivity are attributed in this and subsequent sections to specific factors operating in addition to activation by azine-nitrogen. Another possible source of variation may be a decrease in selectivity with increasing reactivity of one or both reagents, an effect established in electrophilic aromatic... 

The methodology based on the addition of nucleophiles at the a- and y -positions of A -alkylpyridinium salts to give substituted 1,2- and 1,4-dihydropyridines (often not isolated) as intermediates, respectively, which can be further elaborated into complex polycyclic alkaloids, was reviewed by Joan Bosch and M.-Lluiesa Bennasar in 1995 (95SL587). 

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