Addition of nucleophiles

J-Tosyloxy. d -steroids, e.g. O-tosylcholesterol, give 3,5-cyclosteroids (— /-steroids) on addition of nucleophiles. Internal hydroxyl displacement, e.g. with PClj, leads to 3fi-substituted products or overall retention of configuration at C-3 by rearrangement of the 6/5 substituent (E.M. Kosower, 1956). 

Like butadiene, allene undergoes dimerization and addition of nucleophiles to give 1-substituted 3-methyl-2-methylene-3-butenyl compounds. Dimerization-hydration of allene is catalyzed by Pd(0) in the presence of CO2 to give 3-methyl-2-methylene-3-buten-l-ol (1). An addition reaction with. MleOH proceeds without CO2 to give 2-methyl-4-methoxy-3-inethylene-1-butene (2)[1]. Similarly, piperidine reacts with allene to give the dimeric amine 3, and the reaction of malonate affords 4 in good yields. Pd(0) coordinated by maleic anhydride (MA) IS used as a catalyst[2]. 

Addition of nucleophiles to both activated and unactivated alkenes is catalyzed by Pd(II). Addition of alcohols or AcOH to alkenes bearing EWGs is catalyzed by PdCl2(PhCN)2 to give the corresponding ethers and esters. The addition of an alcohol to the cyclic acetal of acrolein 82 to give the ether 83 is also possible with the same catalyst[64]. Amines add to the vinylic ether 84 to give 85, but not to simple alkenes[65]. 

Addition Reactions. The addition of nucleophiles to quinones is often an acid-catalyzed, Michael-type reductive process (7,43,44). The addition of benzenethiol to 1,4-benzoquinone (2) was studied by A. Michael for a better understanding of valence in organic chemistry (45). The presence of the reduced product thiophenyUiydroquinone (52), the cross-oxidation product 2-thiophenyl-1,4-benzoquinone [18232-03-6] (53), and multiple-addition products such as 2,5-(bis(thiophenyl)-l,4-benzoquinone [17058-53-6] (54) and 2,6-bis(thiophenyl)-l,4-benzoquinone [121194-11-4] (55), is typical ofmany such transformations. 

Chiral Titanium Complexes. Chiral titanium complexes are useful for the enantioselective addition of nucleophiles to carbonyl groups ... 

The Michael addition of nucleophiles to the carbon—carbon double bond of maleimide has been exploited ia the synthesis of a variety of linear polymers through reaction of bismaleimide with bisthiols (39). This method has been used to synthesize ethynyl-terminated imidothioether from the reaction of 4,4 -dimercaptodiphenyl ether [17527-79-6] and A/-(3-ethynylphenyl)maleimide (40). The chemical stmcture of this Michael addition imide thermoset is as follows ... 

The conjugated stmcture of 1,3-butadiene gives it the abiUty to accept nucleophiles at both ends and distribute charge at both carbon 2 and 4. The initial addition of nucleophiles leads to transition states of TT-ahyl complexes in both anionic and transition-metal polymerizations. 

Addition of nucleophiles to C=N bonds is common in these compounds. 

The addition of nucleophiles to double and triple bond systems is often a convenient way of effecting an intramolecular ring closure. Addition to cyano groups has received considerable attention, as in addition to ring formation it provides a convenient method for the introduction of an amino group. Reaction of methyl Af-cyanodithiocarbimidate with Af-methylaminoacetonitrile resulted in displacement of methanethiol and formation of (314). Sodium ethoxide treatment in DMF converted (314) into a 4-amino-5-cyanoimidazole... 

Table 8.4. Relative Reactivity of Some Ketones toward Addition of Nucleophiles...

Addition of nucleophiles sueh as ammonia or alcohols or their conjugate bases to benzynes takes place very rapidly. These nueleophilie additions are believed to involve eapture of the nueleophile, followed by protonation to give the substituted benzene. ... 

A partial explanation of the above findings must lie in the known ease of addition of nucleophilic reagents to the conjugated double bond of pregn-16-en-20-ones. The amide ion that is a by-product of the reduction probably adds to a portion of the unreduced pregn-16-en-20-one giving the lithium enolate of amino ketone (74). This enolate may well be relatively stable at — 33° and would be protonated to the free 16-amino-20-one during work-up... 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Quite remarkably it was found that all cations yielded the same values, or, to put this another way, the LEER of log against had slope = 1.00 for all cations only the intercepts (log Hjo) differed.Table 7-16 gives values ofiV +. [Additions of nucleophiles to some activated olefins also have been found to correlate with N +, although slopes were different from unity. 

Finally, mention should be made of the addition of nucleophilic reagents to the 1-position of 3,4-dihydro-j8-carbolines, Cyanide has been reported to yield adducts with harmaline, 6-nitroharm-aline, and 2-methylharmalinium salt similarly, hydroxylamine forms adducts with harmaline, 3,4-dihydro-j8-carboline (307 R = H), and l-phenyl-3,4-dihydro-)S-carboline (307 R =... 

Covalent addition of solvent or of nucleophile prior to substitution will alter the reactivity characteristics of the substrate. Covalent addition of nucleophile after substitution will affect the kinetics in a way similar to the formation of 389. Covalent hydration and additions are especially likely to occur in bicyclic azines. (cf. Section IV,B,3,b).ii>i o>i i i4... 

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). 

Ley and Middleton synthesized ketone-functionalized lactam complexes 260 (Scheme 2.64) by sonication of vinylaziridines 259 with Fe2(CO)9 in benzene. These complexes were easily converted into the corresponding (3-lactams 261 by stereoselective addition of nucleophiles such as NaBH4 or trialkylaluminium to the carbonyl group followed by decomplexation with Me3NO [96]. 

As outlined in Section D.2.3.5., the stereochemical outcome of the addition of nucleophilic reagents to chiral aldehydes or ketones is rationalized most plausibly by the Cram-Felkin-Anh model. On the other hand, the corresponding reactions of oxygen- or nitrogen-heterosub-stituted aldehydes or ketones may be interpreted either by the same transition state hypothesis or, alternatively, by Cram s cyclic model. 

The addition of nucleophiles with charge n (Nu", n = 0, -1, -2) to arenediazonium ions can be summarized as shown in Scheme 6-1. In the primary adduct (6.1) Nu" is covalently bonded to the (3-nitrogen. In most - perhaps all - cases the azo group is in the (Z)-configuration. The stability of the primary adduct is critically... 

Structural and Mechanistic Aspects of Additions of Nucleophiles to Diazonium Ions... 

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