Making cyclopropanes

Many natural products and biologically active compounds contain cyclopropane rings: we shall feature just a few. First, a most important natural insecticide, a pyrethrin from the East African pyrethrum daisy, and its synthetic analogue decamethrin, one of the most important insecticides in agriculture. Very low doses of this highly active and non-persistent insecticide are needed.

The ‘ozone’ or ‘iodine’ smell of the sea has nothing to do with O3 or I2. It’s more likely a dictyopterene, a family of volatile cyclopropanes used by female brown algae to attract male gametes. Other cyclopropanes include two natural but highly unusual amino acids. Hypoglycin is a blood sugar level lowering agent from the unripe fruit of the ackee tree. It’s the causative agent of Jamaican vomiting sickness. Don’t eat the green ackee. The second and simpler amino acid is found in apples, pears, and grapefruit, and encourages fruit ripening by degradation to ethylene. Our last and most extraordinary example is an antifungal antibiotic first synthesized in 1996 and containing no fewer than five cyclopropanes. It has the prosaic name FR-900848 but is known unofficially as ‘jawsamycin’.

Most chemical syntheses of compounds containing cyclopropyl groups make use of the addition of a carbene, or carbene equivalent, to an alkene. What do we mean by carbene equivalent? Usually, this is a molecule that has the potential to form a carbene, although it may not actually react via a carbene intermediate. One such example is the zinc carbenoid formed when diiodomethane reacts with zinc metal (most conveniently as a mixture with copper—a ‘zinc–copper couple’). It reacts with alkenes just as a carbene would—it undergoes addition to the π bond and produces a cyclopropane.

The reaction is known as the Simmons–Smith reaction, after the two chemists at the DuPont chemical factory who discovered it in 1958. Even after several decades, it is the most important way of making cyclopropane compounds, although nowadays a variant that uses more easily handled starting materials is often used. Diethyl zinc replaces the Zn/Cu couple of the traditional Simmons–Smith reaction. In this example, a double cyclopropanation on a C2 symmetric diene derived from tartaric acid gives very good stereoselectivity for reasons we will soon discuss.

The mechanism of the Simmons–Smith reaction appears to be a carbene transfer from the metal to the alkene without any free carbene being released. It may look something like this.

Some of the evidence for this comes from a reaction that not only throws light on to the mechanism of Simmons–Smith cyclopropanations, but makes them of even greater value in synthesis. When an allylic alcohol is cyclopropanated, the new methylene group adds stereo selectively to the same face of the double bond as the hydroxyl group.

Allylic alcohols are also cyclopropanated over 100 times faster than their unfunctionalized alkene equivalents. Coordination between the zinc atom and the hydroxyl group in the tran sition state explains both the stereoselectivity and the rate increase. Unfortunately, while the Simmons–Smith reaction works well when a methylene (CH₂) group is being transferred, it is less good with substituted methylene groups (RCH: or R2C:). The carbene derived by metal-catalysed decomposition of ethyl diazoacetate attacks alkenes to introduce a two-carbon fragment into a cyclopropane—an industrial synthesis of ethyl chrysan themate, a precursor to the pyrethrin insecticides , uses this reaction. The diene in the starting material is more nucleophilic (has a higher energy HOMO) than the single alkene in the product, so the reaction can be stopped after one carbene addition.

The intramolecular version of this reaction is more reliable, and has often been used to make compounds containing multiply substituted cyclopropanes. Corey made use of it in a synthesis of sirenin, the sperm-attractant of a female water mould.

As you might imagine, carbenes like this, substituted with electron-withdrawing carbonyl groups, are even more powerful electrophiles than carbenes like: CCl₂, and will even add to the double bonds of benzene. The product is not stable, but immediately undergoes electro cyclic ring opening.

اخر الاخبار

اخبار العتبة العباسية المقدسة

استعدادًا لزيارة الأربعين العتبة العباسية المقدسة تعقد اجتماعًا لتنظيم عمل الهيئات التطوّعية في الصحن الشريف

قسم الشؤون الخدمية يواصل تنفيذ أعمال الوقاية ومكافحة الحشرات في مواقع العتبة العباسية المقدسة

المجمَع العلمي للقرآن الكريم يواصل تنفيذ مشروع بيوت النور القرآني

قسم الشؤون الفكرية يبحث التعاون في مجال البحث مع كلية التقنيات المتعددة في نيجيريا

المزيد

الآخبار الصحية

تسارع الشيخوخة.. متى يبدأ وأي الأعضاء أكثر تأثرا؟

9 مسببات شائعة للالتهاب المزمن قد تهدد صحتك

باحثون يطورون علاجا لهشاشة العظام.. النتائج مذهلة

تحمي من أمراض عديدة.. 6 فوائد لتناول البطاطا الحلوة

المزيد

الآخبار التكنلوجية

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

المعلمون في خطر.. خاصية جديدة في "تشات جي بي تي" تشرح الدروس

بشرى لمرضى الشلل.. شريحة في الدماغ قد تتيح التحكم بالأدوات

مدينة غارقة.. هل يخفي قاع البحر الكاريبي سرّ حضارة مفقودة؟

المزيد

مواضيع ذات صلة

Attack of carbenes on lone pairs

Nitrenes are the nitrogen analogues of carbenes

Rearrangement reactions

Insertion into C–H bondsInsertion into C–H bonds

Carbenes react with alkenes to give cyclopropanes

The structure of carbenes depends on how they are made

Carbenes can be divided into two types

اكتشاف العناصر

العناصر

Diazomethane makes methyl esters from carboxylic acids

Intramolecular radical reactions are more efficient than intermolecular ones

Alkyl radicals from boranes and oxygen