Single enantiomers from diastereoselective reactions

The aldol reactions in the last section made single diastereoisomers from two achiral com pounds. No enantiomerically pure reagents were used, so the reaction had no choice but to give the product diastereoisomer as a racemic mixture of its two enantiomers. In all the other diastereoselective reactions in this chapter, the starting material has been chiral, with the formation of new chiral centres controlled by the configuration of the start ing material. Whatever the diastereoselectivity of the reaction, if the starting material is race mic, so will be the product; if the starting material is enantiomerically pure, so will be the product. The epoxidation of the allylic alcohol in the margin illustrates this point. The reaction starts with racemic material (no stereochemistry is shown at the chiral centre) and makes a racemic product. Of course, we have only drawn one enantiomer—the only way to draw one diastereoisomer is to choose one enantiomer and draw that—but the indication ‘± ‘underneath tells you to expect an equal amount of the other enantiomer as well. Even without this indication, you should be able to work out, in any given case, whether a com pound is racemic or not, providing you know where it comes from. Here the starting material is racemic and the reagent is achiral so the product must be racemic. The example of this reaction earlier was this type of reaction. The starting alcohol was racemic and the product was just one racemic diastereoisomer—the all-cis compound. But if the starting material had been enantiomerically pure, so would the product. One enantiomer gives one enantiomer of the product: the other enantiomer of the alcohol gives the other. Both products are the same diastereoisomer (all cis) but they are mirror images of each other. If you start with enantiomerically pure compounds, the products will be enantiomerically pure as well. We gave an example of this during the discussion of the Felkin–Anh model. The starting material was the natural amino acid isoleucine and was the enantiomer shown. The product of the aldol reaction was therefore also a single enantiomer. The original chiral centre in both these examples is not affected by the reaction and remains unchanged.

It is much more useful to make enantiomerically pure as well as diastereoisomerically pure compounds, particularly in the synthesis of a drug. The strategy used here is to make the start ing material from an enantiomerically pure compound available from nature: in this case an amino acid. These available enantiomerically pure compounds are known collectively as the chiral pool . If you are making an enantiomerically pure compound with more than one stereogenic centre, only one needs be borrowed from the chiral pool, provided diastereoselective reactions can be used to introduce the others with control over relative stereochemistry. Because the fi rst chiral centre has defined absolute configuration, any diastereoselective reaction that controls the relative stereochemistry of a new chiral centre also defines its absolute configuration. We’ll use as an illustration a synthesis of a rare sugar, methyl mycaminoside, containing five chiral centres. Only one chiral centre comes directly from the chiral pool—the rest are intro duced diastereoselectively. The naturally derived, enantiomerically pure compound used as the starting material is (S)-lactic acid. The starting chiral centre, preserved right through the sequence, is ringed in green. The ring was built up using familiar chemistry from acetylated (S)-lactic acid, and a cyclization step introduced the second chiral centre in the final step of the scheme below. The methyl group goes pseudoequatorial on the newly formed ring, while the anomeric effect , induces the methoxy group to prefer the pseudoaxial position.

The third stereogenic centre was controlled by reduction of the ketone from the axial direction to give the equatorial alcohol, which then directed introduction of the fourth and fifth stereogenic centres by epoxidation.

Finally, the simple nucleophilic amine Me₂NH attacks the epoxide with inversion of con figuration to give methyl mycaminoside. The conformational drawing shows that all substitu ents are equatorial except the MeO group, which prefers to be axial because of the anomeric effect. Starting from an enantiomerically pure compound containing one chiral centre, four new chiral centres are introduced in sequence by diastereoselective reactions of various kinds. The final product is necessarily a single enantiomer.

اخر الاخبار

اخبار العتبة العباسية المقدسة

بيان لمكتب المرجعية العليا حول نشر صور السيد السيستاني في الأماكن العامة

متحف الكفيل: إنجاز المرحلة الرابعة من مشروع متحف العتبة العسكرية المقدسة

تضمن عرضًا مسرحيًّا.. شعبةُ الخطابة النسويّة تقيم مجلس عزاء بذكرى شهادة الإمام الحسن (عليه السّلام)

الأمين العام للعتبة العبّاسية المقدّسة يتفقد مجموعة مواكب أمّ البنين (عليها السلام) لخدمة الزائرين

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

The Hammett relationship

Systematic structural variation

Crossover experiments

Labelling experiments reveal the fate of individual atoms

Be sure of the structure of the product

Variation in the structure of the aldehyde

formation of an ester intermediate

formation of an intermediate dimeric adduct

Be sure of the structure of the product

Variation in the structure of the aldehyde

Proposed mechanism C: formation of an ester intermediate

Proposed mechanism B: formation of an intermediate dimeric adduct