Bridgehead Carbanions

In accordance with the electropositive nature of the bridgehead atoms, all di(pyridyl) substituted anions behave like amides with the electron density accumulated at the ring nitrogen atoms rather than carbanions, phosphides or arsenides. The divalent bridging atoms (N, P, As) in the related complexes should in principle be able to coordinate either one or even two further Lewis acidic metals to form heterobimetallic derivatives. According to the mesomeric structures, (Scheme 7), it can act as a 2e- or even a 4e-donor. However, theoretical calculations, supported by experiments, have shown that while in the amides (E = N) the amido nitrogen does function as... 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

Note that by the investigators design, the bridgehead protons ( ) are not acidic, since any resulting carbanion would be orthogonal to the boron 2pz-orbital and thus incapable of 7r-bonding stabilization. 

Evidence in support of a preferred sp3 configuration is provided by the observation that reactions which involve the formation of carbanion intermediates at bridgehead positions often take place readily while those that would have involved the corresponding carbo-cation (sp2) intermediates do not (cf. p. 86). 

Nucleophilic substitution, aliphatic, 31, 45, 77-100 Ag catalysis, 97 allyl halides, 85 ambident nucleophiles, 97 benzyl halides, 84, 91 bridgehead halides, 86 bromomethane, 78 2-bromopropanoate, 94 1-bromotriptycene, 87 carbanions in, 100,288... 

The two bridgehead hydrogens Ha and Hb in the anisaldehyde dithioace-tal (130) have a large difference in their acidities, as indicated by the NMR chemical-shift difference (4.88 and 5.03 ppm). Preparation of the monocarbanion (1 BuLi in THF at -78°C) and quenching with DC1 removed only the higher field hydrogen. The carbanion can be reacted with electrophiles such as primary halides, acid halides, or aldehydes to produce (135). Carbanion generation and alkylation can be repeated on (135) to yield the disubstituted derivative (136) as shown in Scheme 44. 

A hydroxyl group has been introduced at the bridgehead of the bicyclic compound (146) by treating the carbanion with the reagent oxodiperoxy-molybdenum hexamethylphosphoric triamide, pyridine (MoOPH), to give compound (147) (81TL2341). 

Another example of such effect is the increased regioselectivity for alkylation of certain bicydic piperazinediones [33]. The stability difference of the two bridgehead carbanions is due to the third substituent (O vs. CH2) see Eq. 19. ... 

In contrast to benzothiadiazepines 40 (see Scheme 4), the nucleophilic attack of -BuLi on bis(triazolo)thiadiazepine 77 (R = H) (Scheme 14) occurred both at the sulfur atom and at the proton of the seven-membered ring resulting in formation of two ring-opened products <2002MC131>. Carbanion formation at the bridgehead of 78 (R1 = R2 = H) (Scheme 15) is easily achieved by treatment with -BuLi or lithium diisopropylamide (LDA) subsequent alkylation with Mel afforded the monomethylated product 78 (R1 =Me R2 = H) in 54% yield <1981T2045>. 

Bridgehead adamantyl carbanions have been found to be quite elusive. Attempts to generate bridgehead organometallic derivatives of adamantane frequently result instead in the preparation of 1,1-biadamantane 318> 319). 1-Adamantyl lithium may be obtained, however, by the exchange reaction illustrated in Eq. (81). 

Simpkins and coworkers reported the use of chiral bases in the enantioselective generation of bridgehead enolates (Scheme 36)76. Initial studies revealed that external quench protocols were ineffective in trapping the carbanion. Addition of a mixture containing chiral base (R,R) 3 and LiCl to a solution of ketone 55 and TMSC1 at —105 °C gave mono (—)-a-silylated ketone 56 in 76% yield and >96% ee. 

Azocanes with nitrogen at a bridgehead such as fused azocane 289 were prepared starting from /V-protected amino aldehydes 286. Those amino aldehydes were converted into allylic alcohols by the classical Morita-Baylis-Hillman reaction or by condensation with selenium-stabilized carbanions, followed by oxidation <2007JOC5608>. Fused azocane 289 was prepared in good yield as described in Scheme 120. Formation of [ z, ,0]-bicyclic structures via these reactions is general and the stereochemistry of the starting amino-aldehyde is preserved. 

MoOPH (Section 2.3.2.1.2.ii) may be a suitable reagent for lactam enolate hydroxylation. This is suggested by the oxidation of lactam (148). Cleariy the label enolate is not strictly applicable to the bridgehead carbanion and it is likely that more forcing conditions would be necessary for genuine enolate hydroxylations. It is not clear whether V-oxidation would then emerge as a source of problems. 

Frequently, bond cleavage is used for R-Hal —> R-H dehalogenations [74], and the formation of carbanions [75]. More seldom encountered are reactions of n acceptors that have the a bond spatially well separated and that depend on long-range ET. Such a situation occurs in phenyl-substituted alkyl chlorides [76], and bridgehead halides [77] with various redox relay functions (e.g. a nitroaryl group) [78]. 

Second, all of the atoms involved in resonance stabilization must be coplanar. Thus, the exocyclic carbanion is not in a position geometrically favorable for reaction with the carbonyl group. Third, in 7-54 there is a double bond at a bridgehead that involves considerable strain energy. 

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