Linear 1,3-dipoles

In the Diels–Alder reaction, the dienes had to have an s-cis conformation about the central single bond so that they were already in the shape of the product. Many useful 1,3-dipoles are actually linear and although their 1,3-dipolar cycloadditions look very awkward they still work well. We shall start with the nitrile oxides, which have a triple bond where the nitrone had a double bond.

As you might expect, this [3 + 2] cycloaddition is a reaction involving the HOMO of the alkene and the LUMO of the nitrile oxide so that the leading interaction that determines the structure of the product is the one in the margin. If there is stereochemistry in the alkene, it is faithfully reproduced in the heterocyclic adduct as is usual for a concerted cycloaddition.

Both partners in nitrile oxide cycloadditions can have triple bonds—the product is then a stable aromatic heterocycle called an isoxazole.

Reduction of the N–O bond and the C=N double bond of the nitrile oxide cycloadducts produces useful amino alcohols with a 1,3-relationship between the two functional groups. As the N–O bond is the weaker of the two, it is alternatively possible to reduce just that and leave the C=N bond alone. This gives an imine, which usually hydrolyses during work-up.

Any stereochemistry in the adduct is preserved right through this reduction and hydrolysis sequence: you might like to compare the products with the products of the stereoselective aldol reactions .

We shall end this section with the illustration of a beautiful intramolecular 1,3-dipolar cycloaddition that was used in the synthesis of the vitamin biotin. Starting at the beginning of the synthesis will allow you to revise some reactions from earlier chapters. The starting material is a simple cyclic allylic bromide that undergoes an efficient SN2 reaction with a sulfur nucleophile. In fact, we don’t know (or care!) whether this is an SN2 or SN2′ reaction as the product of both reactions is the same. Notice that it is the sulfur atom that does the attack—it is the soft end of the nucleophile and better at SN2 reactions. The next step is the cleavage of the ester group to reveal the thiolate anion.

The nucleophilic thiolate anion does a conjugate addition on to a nitroalkene

Now comes the exciting moment. The nitroalkene gives the nitrile oxide directly on de hydration with PhN=C=O and the cycloaddition occurs spontaneously in the only way it can, given the intramolecular nature of the reaction.

In the margin we show how this reaction works—the nitrile oxide comes up from the underside of the seven-membered ring, pushing the black hydrogen atoms upwards and making all the rings join up in a cis fashion. Next the cycloadduct is reduced completely with LiAlH₄ so that both the N–O and C=N bonds are cleaved. This step is very stereoselective so the C=N reduction probably precedes the N–O cleavage and the hydride has to attack from the outside (top) face of the molecule. These considerations are explored more thoroughly.

The sulfur-containing ring and the stereochemistry of biotin are already defined. In the seven steps that follow, the rest of the molecule is assembled. The most important is the break ing open of the seven-membered ring by a Beckmann rearrangement.

اخر الاخبار

اخبار العتبة العباسية المقدسة

مركز دار العلم للدراسات العقدية والتاريخية يقدم خدمات متنوعة لزائري الأربعين

متحف الكفيل يعلن عن استقبال أكثر من 130 ألف زائرٍ خلال زيارة الأربعين

فرقة العباس (عليه السلام) تنظم مسيرة عزائية وتحصي خدماتها المقدمة لزائري الأربعين

معتمدة على منظومة عدّ إلكتروني دقيقة العتبة العباسية المقدسة تعلن أعداد الزائرين المشاركين في إحياء زيارة الأربعين

المزيد

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9 أسباب شائعة للرؤية الضبابية يجب معرفتها

تتناولها كل يوم.. 10 وجبات شائعة غنية بـ"السكر الخفي"

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المزيد

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هل تشغيل تكييف السيارة على "الحد الأقصى" ضار؟

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بالذكاء الاصطناعي.. باحثون يبتكرون مضادات جديدة لنوعين من العدوى البكتيرية

فيتامين سي والتجاعيد.. طبيب يكشف وقت الاستخدام الصحيح

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مواضيع ذات صلة

The future of organic chemistry

The synthesis of oseltamivir

The synthesis of indinavir

Chemistry vs viruses

Terpenes are volatile constituents of plants

Aromatic polyketides

Fatty acids and other polyketides are made from acetyl CoA

Benzyl isoquinoline alkaloids are made from tyrosine

Pyrrolidine alkaloids are made from the amino acid ornithine

Alkaloids are made by amino acid metabolism

The shikimic acid pathway

Phosphoenolpyruvate