Regard five-membered rings with two or more sp3 carbons as flat

When there are two or three trigonal carbons in the ring, the ring is flatter and reactions such as enolate alkylation and conjugate addition give excellent stereoselectivity even with a sim plecyclopentane ring. Unsaturated five-membered lactones (known as ‘butenolides’) give a very clear illustration of stereochemically controlled conjugate addition. There is only one possible stereogenic centre and the ring is almost planar so we expect nucleophilic attack to occur from the less hindered face. Cuprates are good nucleophiles for this reaction and here Me2CuLi adds to the unsaturated lactone.

With a single enantiomer of the starting material below, the product is the single enantiomer of an insect pheromone.

It is not even necessary to have a stereogenic centre in an unsaturated ring if we want to create stereochemistry. A tandem conjugate addition and alkylation creates two new stereo genic centres in one operation. The conjugate addition of a lithium cuprate makes a lithium enolate, which will react in turn with an alkyl halide. The product is usually trans.

The key step is the alkylation of the enolate intermediate. Enolates in five-membered rings are almost flat and the incoming orange allyl bromide prefers the less hindered face away from the recently added green vinyl group. Our main example of enolate reactions in five-membered rings is one of some general importance. It illustrates how stereochemical information can be transmitted across a ring even though the original source of that information may be lost during the reaction. That may sound mysterious, but all will become clear. The fi rst reaction is to make a five-membered cyclic acetal from an optically active hydroxy-acid. Our example shows (S)-(+)-mandelic acid reacting with t-BuCHO.

Acetal formation involves nucleophilic attack of the OH group on the aldehyde so there is no change at the stereogenic centre. The stereochemistry of the new (acetal) centre may surprise you—why should the cis isomer be so favoured? This is a conformational effect as both substituents can occupy pseudoequatorial positions. Now, if we make the lithium enolate with LDA, the original stereogenic centre is destroyed as that carbon becomes trigonal and planar. The only stereogenic centre left is the newly introduced one at the acetal position.

The ring is now essentially flat, owing to the C=C bond within it, and reaction of the enolate with an electrophile is again a simple matter of addition to the face of the enolate opposite to the t-butyl group.

If the acetal is now hydrolysed, the new stereogenic centre is revealed as an alkylated version of the starting material. It may appear that the alkylation has happened stereospecifically with retention, but what has really happened is that the new stereogenic centre in the acetal intermediate has relayed the stereochemical information through the reaction. Five-membered rings also allow us to explore electrophilic attack on alkenes. A simple 4-substituted cyclopentene has two different faces—one on the same side as the substituent and one on the opposite side. Epoxidation with a peroxy-acid occurs preferentially on the less hindered face.

In the transition state (marked ‡) the peroxyacid prefers to be well away from R, even if R is only a methyl group (the selectivity is 76:24 with R=Me). The opposite stereoselectivity can be achieved by bromination in water. The bromonium ion intermediate is formed stereoselectively on the less hindered side and the water is forced to attack stereospecifically in an SN2 reaction from the more hindered side.

Treatment of the product with base (NaOH) gives an epoxide by another SN2 reaction in which oxygen displaces bromide. This is again stereospecific and gives the epoxide on the same side as the R group.

Two substituents on the same side of a five-membered ring combine to dictate approach from the other side by any reagent, and the two epoxides can be formed each with essentially 100% selectivity.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تحيي ذكرى شهادة الإمام السجاد (عليه السلام)

العتبة العباسية المقدسة تنشر لافتات خاصة بذكرى شهادة الإمام زين العابدين (عليه السلام)

قسم شؤون المعارف ينظّم دورة مختصة بتحقيق المخطوطات لطلبة الحوزة العلمية النجف الأشرف

قسم التطوير ينظم دورات وورشا تدريبية لطلبة أكاديمية التطوير الإداري

المزيد

الآخبار الصحية

دراسة علمية تكشف مفاجأة حول الأسباب الحقيقية للسمنة

دراسة: الأطباء يتجاهلون "سببا شائعا" لارتفاع ضغط الدم

نظامك الغذائي غني بالبروتين؟.. احذر هذه الآثار الجانبية

لا تتجاهلها.. أعراض تنذرك بأنك مهدد بالإصابة بالسكري

المزيد

الآخبار التكنلوجية

ISOFIX: معيار الأمان الذهبي لمقاعد الأطفال في السيارات

هل المحرك الأكبر دائمًا الأفضل للسيارة؟

اختبارات ناجحة لمحرك "VK-800" الروسي وتطويره لطائرة بايكال الخفيفة

رئيس إنفيديا: الذكاء الاصطناعي الصيني "محفز للتقدم العالمي"

المزيد

مواضيع ذات صلة

Reactions of cis-decalins

cis-Fused rings

Reactions that break open bridged molecules can preserve stereochemistry

Bridged bicyclic rings

Five-membered ketones are flexible

Only axial attack is possible with cyclohexenes

Axial or equatorial attack is possible on a cyclohexanone

Diastereotopic protons in acyclic compounds

Spotting diastereotopic protons in the NMR spectrum

How to tell if protons are homotopic, enantiotopic, or diastereotopic

The size of the geminal coupling constant

Geminal (2J) coupling