Synthesis of β-lactams by [2 + 2] cycloadditions

Now the disconnections are really different—one requires addition of a ketene to an imine and the other the addition of an isocyanate to an alkene. Isocyanates are like ketenes, but have a nitrogen atom instead of the end carbon atom. Otherwise the orbitals are the same.

And the good news is that both work, providing we have the right substituents on nitrogen. The dichloroacetyl chloride trick works well with imines and, as you ought to expect, the more nucleophilic nitrogen atom attacks the carbonyl group of the ketene so that the regio selectivity is right to make β-lactams.

If both components have one substituent, these will end up trans on the four-membered ring just to keep out of each other’s way. This example has more functionality and the product is used to make β-lactams with antibiotic activity.

You will notice that in both of these examples there is an aryl substituent on the nitrogen atom of the imine. This is simply because N-aryl imines are more stable than their NH ana logues. When we wish to make β-lactams by the alternative addition of an isocyanate to an alkene, a substituent on nitrogen is again required, but for quite a different reason. Because alkenes are only moderately nucleophilic, we need a strongly electron-withdrawing group on the isocyanate that can be removed after the cycloaddition, and the most popular by far is the chlorosulfonyl group. The main reason for its popularity is the commercial availability of chlorosulfonyl isocyanate. It reacts even with simple alkenes.

The alkene’s HOMO interacts with the isocyanate’s LUMO, and the most electrophilic atom is the carbonyl carbon so this is where the terminal carbon atom of the alkene attacks. The chlorosulfonyl group can be removed simply by hydrolysis under mild conditions via the sulfonic acid. With a more electron-rich alkene—an enol ether, for example, or the following example with its sulfur analogue, a vinyl sulfide—the reaction ceases to be a concerted process and occurs stepwise. We know this must be the case in the next example because, even though the starting material is an E/Z mixture, the product has only trans stereochemistry: it is stereo selective rather than stereospecific, indicating the presence of an intermediate in which free rotation can take place.

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