Bridgehead carbanion alkylation

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. ... 

Alkylation at the bridge positions of a bicyclobutane has been well documented. However, with the fused bicyclobutane (191) bridgehead-substitution products are obtained only at low temperature. At temperatures approaching 0°C the initially produced bridgehead carbanion suffers skeletal rearrangement and products with the structure (192) are obtained. ... 

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. 

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. 

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>. 

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]. 

---