Hydrogen bridgehead

Assume that the bond dissociation energy of the bridgehead hydrogens in each bicycloalkane is 104kcal/mol. Indicate and discuss any other assumptions you have made. 

In bicyclic systems, bridgehead hydrogens are most resistant to replacement by fluorine Cobalt trifluonde converts l//-nonafluorobicyclo[3.2.0]hept-6-ene to... 

Examine the geometry of norcarane. What is the conformation of the cyclohexane ring Choose a name (chair, twist boat, half-chair, etc. see Chapter 5, Problem 4) that accurately describes its shape. The bridgehead hydrogens in norcarane are cis. Do you think a trans stereoisomer is possible Explain. 

Make a sketch of each decalin isomer, and label the orientation of the bridgehead hydrogens with respect to each ring (equatorial or axial). Build a plastic model of each isomer and determine its conformational flexibility (a flexible molecule can undergo a ring flip, but a locked molecule cannot). Is flexibility responsible for stabihty ... 

The pronounced acidity of the bridgehead hydrogen atoms in 4 (R = H) facilitates the regio-selective introduction of electrophiles. Rearrangements of 4 (R = H, Me, CHO, C02Me) catalyzed by dicarbonyldichlororhodium(I) lead to 4-substituted 1-benzothiepins 5,10 except in the case of R = Me where a mixture (1 1.3) of 3- and 4-methyl-l-benzothiepin is obtained (total yield 98 %). In the case of the dimethyl-substituted derivative 8 (R1 = R2 = Me), however, the rhodium(I)-catalyzed isomerization reaction leads to the thiophene isomer. 

Entry 5 is an example of use of an a-trimethylsilylallyl group to prepare a vinylsilane. The stereochemistry is consistent with a cyclic TS having the trimethylsilyl substituent in a quasi-axial position to avoid interaction with the bridgehead hydrogen of the bicyclic ring. 

In mechanism (8.43) the bridgehead hydrogens of barrelene should be found at the a positions of semibullvalene (2a, 0/3,0y). Mechanism (8.44) can give three different hydrogen-label distributions. If the final bond formation is concerted with bond fission, and bond fission and formation take place at the same carbon atom [mechanism (8.44A)], the label distribution should be (la, 0/3, ly). If bond formation is concerted with bond fission but with a preference for bond formation at the carbon allylic to bond fission [mechanism (8.44B)], the label distribution should be (2a, 0/3, Oy). If there is a symmetric allylic biradical which has a finite existence [mechanism (8.44AB)], then the hydrogen-label distribution should be (1.5a, 0/3,0.5y). 

Obviously, the advantages of this new synthetic method are i) valence isomerization can be performed under very mild conditions and ii) due to the fairly strong acidity of the bridgehead hydrogens of a bicyclobutane moiety, some substituents can be introduced regioselectively. Nevertheless, one serious disadvantage of this synthesis is the limitation of its applicability Thus, the formation of the precursor bicyclobutane derivatives is limited only to 46 and 56, and many attempts to prepare bicyclobutane precursors from other thiapyran derivatives have been unsuccessful so far. 

The well established chemistry of acyclic secondary-alkyl peroxides 12> suggested that bases should catalyse the isomerization of related bicyclic peroxides to cyclic hydroxyketones 62 via abstraction of bridgehead hydrogen and heterolysis of the peroxide bond (Eq. 48). 

The twice aromatic analog 71 of the propellane 60 containing cyclohexane rings, 5) (in which there are, of course, no bridgehead hydrogens), has been obtained from the tetrabromide and 1,2-benzenedithiol. Again no dispiran is formed 20. ... 

The larger (Z,Z)-l,5-cyclononadiene (169) reacts141 stereoselectively with PhSeCl in AcOH to give the substituted hydrindan 170 (equation 138). In consideration of the anti addition mode of selenenyl reagents to double bonds, the transannular reactions of 169 have been rationalized on the basis of the two reaction intermediates, 171 or 172, which are liable to place the PhSe- and AcO- groups in a cis- 1,4-relationship and trans to the bridgehead hydrogen (equation 139). The preferential formation of 170 has thus been attributed to the fact that the pathway via 172 should involve a boat transition state. 

In the i r-acetyl-7-azabicyclo[2.2.1]heptadiene derivative (12), restricted rotation about the N-CO bond makes the bridgehead hydrogen atoms at C-1 and C-4 nonequivalent, so that they give rise to two equal intensity signals in the NMR spectrum.N-Acetyl- and N-nitroso-7-azabicyclo[2.2.1]heptanes [(35) and (38)] show the same effect. From the coalescence temperatures (>50°) the free energy barriers to internal rotation were calculated to be 17.4, 17.1, and 16.5 kcal mole for 12,35, and 38, respectively. These values are slightly lower than those measured for analogous acyclic amine derivatives, A,A-dimethylaceta-mide and N,N,-dimethylnitrosamine, respectively. 

Hexahydro-8//-pyrido[l,2-6]pyridazin-8-ones (23) are rrans-fused bicycles. The H NMR signal for the bridgehead hydrogen appears as triplet in the range of 3.3-3.5 ppm (7 11-12 Hz) and display further splitting [87JCS(P1)2511]. 

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. 

Treatment of adamantane (2) with sulfur tetrafluoride results in the replacement of one, two or three bridgehead hydrogen atoms by fluorine the degree of fluorination depends on the reaction temperature. When the reaction is conducted in hydrogen fluoride solution, substitution of all four bridgehead hydrogens occurs at relatively low temperature.185... 

Adamantanecarboxylic acids, on treatment with sulfur tetrafluoride, react in a conventional manner to give (triiluoromethyl)adamantanes (see Section 8.2.4.1.). However, in the presence of anhydrous hydrogen fluoride in large excess, substitution of bridgehead hydrogen atoms by fluorine occurs in addition to fluorination of carboxylic acid groups di- or trifluoro(tri-fluoromethyl)adamantanes 7 and 8 arc obtained in one step.8 119186... 

Replacement of bridgehead hydrogen atoms by fluorine is common for various derivatives of adamantane, e.g. adamantanones,119 e.g. 10, adamantylacetic acids,186 e.g. 11, and others.8, l87... 

Evidence for the configurations, i.e. the cis/trans relationship of a substituent with respect to the bridgehead hydrogen atoms, has also been presented. An a priori estimation of the relative stabilities of isomeric substituted indolizidines, assuming a trans junction between the rings, led to the conclusion that equatorial substituents in the six-membered ring and pseudo equatorial substituents in the five-membered ring are thermodynamically favoured. 

A revised structure for the secoiridoid xylomollin (176) has been proposed on the basis of lH coupling constant data and the revised trans-fused arrangement was confirmed by crystallographic analysis (78JA7079). Both rings are in a chair conformation and the bridgehead hydrogen atoms are disposed trans to each other. 

A crucial factor in this synthetic strategy is the fact that only a single diastereomer is formed The rm-butyl group in the bicyclic pro line derivative is cis to the bridgehead hydrogen atom. 

In bicyclie system 7 the bridgehead hydrogen atom is made acidic by the neighboring carbonyl group. Deprotonation with LDA results in enolate 20, the nucleophilic center of which is attacked from the si side. This Ik- 1,3-induction causes the tert-butyl group and the newly introduced allylic group to be cis to each other in product 9. 

Exo-endo additions of organic azides to the norbornene skeleton and other bridged bicyclic systems can be easily differentiated from the NMR spectra of the adducts. The endo protons (exo adducts) of the norbornane do not couple with the bridgehead hydrogens.386 The endo protons in position 3a and 7a of adduct 65 exhibit an AB spectrum. The lack of coupling with the bridgehead protons is a result of a dihedral angle of 82°.25,96 Based on this, the exo form of cycloadduct 66 exhibits symmetrical doublets centered at 8 4.60 and... 

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