Exocyclic double bonds, control

The crucial element of these syntheses is control of the stereochemistry of the exocyclic double bond on the basis of the stereochemistry of migration of a substituent from boron to carbon. Discuss the requirements for a stereoselective synthesis, and suggest how these requirements might be met. 

In this connection, our finding that the allylic mercury intermediate represents the only isolated product following reaction in THF, CH2CI2, or HMPA is pertinent. The generation of this species appears to be rapid in all media. The ensuing step in which Hg(II) is reduced to Hg(O) likely serves as the rate-determining step. If so, the role of nonpolar benzene may be to stabilize the transition state and accelerate the overall rate. No allylic alcohol having an exocyclic double bond was formed, a feature that hints to the possible operation of thermodynamic control. 

Iminium ion-vinylsUane cyclization. This reaction can be used to control the configuration of exocyclic double bonds /i to the nitrogen function of alkaloids. Thus, reaction of the (Z)- and (E)-vinylsilanes 1 and 2 with paraformaldehyde (excess) and tf-camphor-10-sulfonic acid proceeds with >98% retention of configuration to give 3 and 4, respectively. The latter product is identical with the natural indoloquinolizidine alkaloid deplancheine. ... 

The addition of dichlorocarbene to polycyclic isopropylidene di- or polyenes proceeds re-gioselectively at the nucleophilic exocyclic double bond. The ratio oisyn- and unri-isomers formed is controlled by both steric and electronic effects, e.g. formation of 27. ... 

A solution of Pd(dba)2 (1.75 g, 3.0 mmol), t-Bu(i-Pr)2P (560 mg, 3.0 mmol), methylenecyclopropane(43.3 g, 0.8 mol) and diethyl fumarate (135.2 g, 0.786 mol) in anhyd toluene (100 mL), was pumped through a stainless steel capillary tube heated to I50°C (temperature control). The pumping rate, as well as length and diameter of the tube, was adjusted in order to achieve a reaction time of 27 min in the hot zone of the tube. Subsequent fractionating distillation of the dark-red mixture yielded a forerun of toluene, followed by a main fraction (172.3 g bp 60-65 °C/10 Torr) consisting of toluene (0.9%), diethyl fumarate (1.1%), trans-S (R = Et 96.5%), diethyl tranj-4-methylcyclopent-3-ene-l,2-dicarboxylate (0.5%) and cw-8 (R = Et 1.0%), as determined by GC analysis. In order to prevent an increase of isomerization of the exocyclic double bond to yield the cyclopentene product, the bath temperature during distillation should not rise above 90°C. The yield of trans-S is 166.3 g (93.6%). 

Vinylsilanes react with acetals in the presence of Lewis acids to give allylic ethers, which go on to react further. Intramolecular reactions are less susceptible to this difficulty and provide an opportunity for controlling the configuration of exocyclic double bonds (Scheme 51). As usual with vinylsilanes, the... 

Efforts have been made to stabilize the 2,3-bismethylene-2,3-dihydrothiophene system by introducing suitable substituents. Thus the compound (297) with phenyl groups at the exocyclic double bonds was generated by base-catalyzed elimination of methanol from (296) <91ACS9I9>. However, (297) also dimerized easily and the only isolable product (30%) was the spiro compound (298) (Scheme 55). This corresponds to the exo-addition of the diene system to the 3-methylene bond of another molecule. The cycloaddition appears to be orbital symmetry controlled. Only one isomer was obtained. Similarly, (297) could be trapped by means of norbornene cycloaddition led to the exo-adduct in 40% yield. 

The exocyclic C — C double bond in the chlorin can be reduced by catalytic hydrogenation in tetrahydrofuran/water in the presence of palladium(II) acetate with triethoxysilane as hydrogen source to yield under kinetic control cw-stereoisomers, which can be transformed by treatment with /)-toluenesulfonic acid in methanol to the thermodynamically favored trans-isomers.27d... 

Reaction of p-nitrobenzenesulfonyl azide with alkylidenecycloalkanes 22-25187 does not yield isolable triazolines as expected, but the reaction products derived from alkenes 22 and 23 suggest a single triazoline intermediate, whereas in the case of tetrasubstituted derivative 24 both possible reaction modes are present,187 owing to weak double bond dissymmetry. Product analysis from 25 indicates some conflict between electronic and steric control in the addition, but provides evidence that electronic factors are much more important than steric effects in controlling regioselectivity.187 Reaction of the exocyclic olefins 22 and 23 appears to be controlled more by the interaction of the LUMO of the azide and the HOMO of the alkene.187 p-Nitrobenzenesulfonyl azide is reported to react with members of the novel... 

The proton serves as the simplest electrophile to displace the silyl group stereo- and regioselectively. Numerous conditions have been used for the electrophilic protodesilylation of allyl- and vinylsilanes19. ( )-vinyl sulfones 2 are prepared from the silylallylic sulfones 1 in the presence of protic acids in high yield (equation l)34. Diastereoselective protodesilylation of allylsilane 3 gives 4 with excellent control of the geometry of the double bond exocyclic to the ring (equation 2)35. 

The exocyclic C=C double bond of the 1,4-dithiafulvenes (263) can be selectively hydrogenated under controlled conditions in an acidic medium (Zn/glacial acetic acid), the product being 295. The ease with which the postulated intermediate 1,3-dithiolium salts (264) accept the hydride ion has been adduced as evidence that the resonance stabilization of these ions cannot be very strong.159... 

There appears to exist only one single example of substrate-controlled diastereoselection in the conjugate addition to allenoates7 Base-catalyzed addition of methanol to the steroid allene 11 afforded only one of the two possible diastereomeric products in 95% yield. Unfortunately, the configuration around the exocyclic C —C double bond [( )/(Z)] of 12 was not established7. 

Stercocontrol in the addition of formaldehyde to a double bond exocyclic to a five-membered ring has also been demonstrated, forming one new stereocenter with control lower than in the previous example76. The i-isomer of the starting material afforded mainly the 1,2-disubstitut-ed cyclopentene derivative 9. 

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