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• Therefore the transition metal adds to the double bond to result in the Markovnikov product.
• Even the water participates while a work-up with potassium iodide completes the reaction.
• Which reaction proceeds adding a triphenylphosphine species to an aldehyde?
In the first reaction step the enol ether is transformed into an aldehyde. This sequence is named solvomercuration/demercuration.19
(7 och3 $í2
÷îñí3 -H9'2 i
' 1 55
B: Aryl^PPh3 ©
C: Alkyl^PPh3 ©
Therefore mercury(II) acetate interacts as an electrophilic transition metal with the nucleophilic alkene to form the three-membered ring 52. This mercurinium ion is opened by relatively feeble nucleophiles like alcohols - or in this reaction water. Similar to a hydroboration the attack happened at the more substituted end of the mercurinium ion according to Markovnikov’s rule. To get rid of the metal, solid potassium iodide is added. This means insoluble mercury(II) iodide is formed, followed by loss of the methoxy group and formation of enol ether 54, which subsequently tautomerizes to the desired aldehyde 55.
Next again a Wittig reaction succeeds. Aldehyde 55 is directly converted to a 3:1 mixture of E- and Z-enynes 16 upon exposure to the in situ generated Wittig salt 15. The Ë÷ sorrier is built as main product, passing the ««//-configurated oxaphosphetane 56.
What drives the reaction to an E- or Z-alkene?
Generally the stereoselectivity of the [2 + 2]-cycloaddition depends on the ylide. They are divided into three types: A) those with conjugating or anion stabilizing substituents adjacent to the negative charge, for example a carbonyl group (so called stabilized ylides 57), B) those with substituents having only slight stabilizing properties (semistabilized ylides 59) and C) those without a stabilizing neighbor group (unstabilized ylides 60). The extra stabilization of the first sort of ylides is represented by an alternative enol-type structure 58. These ylides can be stored for months and need not to be generated in situ like 59 and 60. To anticipate the solution a general rule is:
- with stabilized ylides the Wittig reaction is ^-selective.
- with unstabilized ylides the Wittig reaction is Z-selective.
- semistabilized ylides produce mixtures of E- and Z-olefines.
To explain this phenomenon, there are two seperate processes to
consider. The first and most important one for this reason is the Alkyl ^^PPh3
formation of the oxaphosphetane. The addition of the ylide to the © + R1cho
aldehyde can, in principle, produce two isomers with either a Z or E J
substituted double bond. The following elimination step is stereo- Ph P 0
specific, with the oxygen and phosphorus departing in a ,vv«-periplanar transition state. With unstabilized ylides the syn diastereomer of the R 61
oxaphosphetane similar to 61 is formed preferentially. This step is syn|
kinetically controlled and therefore irreversible, and predominantly the Z-alkene 62 that results reflects this.
On the other hand the stability of 57 causes the reaction leading to a reversible oxaphosphetane where the isomers 63 and 65 can interconvert via the starting material. The stereoselectivity in this step is thermodynamically controlled. The more stable four-membered ring 0
is anti 65, with the bulky groups on opposite sides of the ring. The J^^®Ph3
product of this reaction after elimination of triphenylphosphine oxide R0 e
is only the E-alkene 66. 57
This explains the moderate selectivity of only 3:1 obtained here. js
Because of the triple bond adjacent to the negative charge 15 rather Ph3PjO Ph3PjrO
belongs to the semistabilized ylides Ñ than to category A, resulting in N--' '•> Ó^'-,
the production of E/Z-mixtures. Here neither the kinetically nor the í°ãÑ 63 R R02c 65 R
:slow I fast
thermodynamically controlled pathway dominates.
Some stabilized ylides are too stable to be very reactive. In this case
phosphonates are used instead of phosphonium salts. For the Horner-
Wadsworth-Emmons-reaciion see Chapter 2. R02C R' R02'
ro2c' r1 ro2c/^r
mixture of E/Z isomers
1.5% HF, CH3CN/CH2CI2 (4:1), 0°C, 15 min; r. t„ 1 h, 92 %
2. TBAF, THF,
-78 °C, 30 min; -78 °C -» 0 °C,
30 min, 92 %
• The aim of these steps is the removal of both silyl protecting groups.
• Which conditions belong to which protecting group and for what reason?
Removal of the tri-wo-propylsilyl (TIPS) and tert-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.ICI The diastereomers are not separated before the desilylation process; therefore even a 3:1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its E-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction.