Making single diastereoisomers using stereospecific reactions of alkenes

The essence of the definition we have just stated is much easier to grasp with some familiar examples. Here are two.

• SN2 reactions are stereospecific: they proceed with inversion so that the absolute stereochemistry of the starting material determines the absolute stereochemistry of the product.

• E2 reactions are stereospecific: they proceed through an anti-periplanar transition state, with the relative stereochemistry of the starting material determining the geometry of the product.

Both of these examples are interesting because they show how, once we have some stereo chemistry in a molecule, we can change the functional groups but keep the stereochemistry— this is the essence of a stereospecific reaction. In the second example, we change the bromide to a double bond, but we keep the stereochemistry (or ‘stereochemical information’) because the geometry of the double bond tells us which bromide we started with. This is a good place to begin if we want to make single diastereoisomers because we can reverse this type of reaction: instead of making a single geometry of alkene from a single dias-tereoisomer, we make a single diastereoisomer from a single geometry of double bond. Here is an example of this— again, one you have already met. Electrophilic addition of bromine to alkenes is stereospecific and leads to anti-addition across a double bond. So, if we want the anti-dibromide we choose to start with the trans double bond; if we want the syn dibromide we start with the cis double bond. The geometry of the starting material deter mines the relative stereochemistry of the product.

Iodolactonization has a similar mechanism; notice how in these two examples the geometry of the double bond in the starting material defines the relative stereochemistry highlighted in black in the product.

For a stereospecific alkene transformation, choose the right geometry of the starting mat erial to get the right diastereoisomer of the product. Don’t try to follow any ‘rules’ over this— just work through the mechanism. Now for some examples with epoxides. Epoxides are very important because they can be formed stereospecifically from alkenes: cis alkenes give cis (or syn) epoxides and trans alkenes give trans (or anti) epoxides.

Epoxides also react stereospecifically because the ring-opening reaction is an SN2 reaction.

A single diastereoisomer of epoxide gives a single diastereoisomer of product.

Leukotrienes are important molecules that regulate cell and tissue biology. Leukotriene C4 (LTC₄) is a single diastereoisomer with an anti-1,2 , S,O functional group relationship. In nature, this single diastereoisomer is made by an epoxide opening: since the opening is SN2 the epoxide must start off anti and, indeed, the epoxide precursor is another leukotriene, LTA₄.

When Corey was making these compounds in the early 1980s, he needed to be sure that the relative stereochemistry of LTC4 would be correctly controlled, and to do this he had to make a trans epoxide. Disconnecting LTA4 led back to a simpler epoxide.

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 27: reduction of an alkynyl alcohol with LiAlH4. Here is the full syn thesis: alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم رعاية الصحن الشريف ينهي استعداداته الخاصة بزيارة الأربعين

قسم الإعلام ينظم دورة تخصصية في تقنيات الذكاء الاصطناعي لعددٍ من منتسبيه

القسم النسوي بمجمع أبي الفضل العباس (عليه السلام) ينهي الاستعدادات لاستقبال زائرات الأربعين

قسم الشؤون الفكرية ينظّم ورشة تدريبية عن الالتزام والانضباط في الخدمة لفتية الكفيل

المزيد

الآخبار الصحية

علامات فارقة بين النوبة أو السكتة القلبية.. ماهي؟

الفلفل الأحمر.. سعرات حرارية منخفضة وفوائد صحية عديدة

8 أعراض إذا شعرت بها.. اذهب للطوارئ فورا !

تعرف على أكثر 8 أماكن اتساخا في المنزل

المزيد

الآخبار التكنلوجية

إنتاج الهيدروجين الأخضر في البحر.. هذه أحدث الدراسات

"ناسا" تخطط لبناء مفاعل نووي على سطح القمر !

ابتكار ومواهب وأموال.. مارك زوكربيرغ يعلن الحرب على أبل

عودة التعاون الفضائي بين روسيا وأميركا.. وبحث ملفات "هامة"

المزيد

مواضيع ذات صلة

Non-linear Hammett plots

A complete picture of the transition state from Hammett plots

Using the Hammett ρ values to uncover mechanisms

Reactions with small Hammett ρ values

Reactions with negative Hammett ρ values

Reactions with positive Hammett ρ values

Equilibria with positive Hammett ρ values

The Hammett substituent constant σσ A

The Hammett relationship

Systematic structural variation

Crossover experiments

Labelling experiments reveal the fate of individual atoms