The
Prins reaction is an
organic reaction consisting of an
electrophilic addition of an
aldehyde or
ketone to an
alkene or
alkyne followed by capture of a
nucleophile.
[1][2][3] The outcome of the reaction depends on reaction conditions (
scheme 1). With water and a protic acid such as
sulfuric acid as the reaction medium and
formaldehyde the reaction product is a
1,3-diol. When water is absent, the cationic intermediate loses a proton to give an
allylic alcohol. With an excess of
formaldehyde and a low reaction temperature the reaction product is a
dioxane. When water is replaced by
acetic acid the corresponding
esters are formed.
History
The original reactants employed by Dutch
chemist Hendrik Jacobus Prins in his 1919 publication were
styrene (
scheme 2),
pinene,
camphene,
eugenol,
isosafrole and
anethole.
In 1937 the reaction was investigated as part of a quest for di-olefins to be used in
synthetic rubber.
Reaction mechanism
The
reaction mechanism for this reaction is depicted in scheme 5. The
carbonyl reactant (2) is
protonated by a protic acid and for the resulting
oxonium ion 3 two
resonance structures can be drawn. This
electrophile engages in an
electrophilic addition with the
alkene to the
carbocationic intermediate 4. Exactly how much positive charge is present on the
secondary carbon atom in this intermediate should be determined for each reaction set. Evidence exists for
neighbouring group participation of the hydroxyl oxygen or its neighboring carbon atom. When the overall reaction has a high degree of
concertedness, the charge built-up will be modest.
The three reaction modes open to this oxo-
carbenium intermediate are:
- in blue: capture of the carbocation by water or any suitable nucleophile through 5 to the 1,3-adduct 6.
- in black: proton abstraction in an elimination reaction
to unsaturated compound 7. When the alkene carries a methylene group,
elimination and addition can be concerted with transfer of an allyl
proton to the carbonyl group which in effect is an ene reaction in scheme 6.
- in green: capture of the carbocation by additional carbonyl
reactant. In this mode the positive charge is dispersed over oxygen and
carbon in the resonance structures 8a and 8b. Ring closure leads through
intermediate 9 to the dioxane 10. An example is the conversion of styrene to 4-phenyl-m-dioxane.[4]
- in gray: only in specific reactions and when the carbocation is very stable the reaction takes a shortcut to the oxetane 12. The photochemical Paternò–Büchi reaction between alkenes and aldehydes to oxetanes is more straightforward.
Variations
Many variations of the Prins reaction exist because it lends itself
easily to cyclization reactions and because it is possible to capture
the oxo-carbenium ion with a large array of nucleophiles. The halo-Prins
reaction is one such modification with replacement of protic acids and
water by
lewis acids such as
stannic chloride and
boron tribromide. The
halogen is now the
nucleophile recombining with the carbocation. The cyclization of certain
allyl pulegones in
scheme 7 with
titanium tetrachloride in
dichloromethane at −78 °C gives access to the
decalin skeleton with the hydroxyl group and chlorine group predominantly in
cis configuration (91% cis).
[5] This observed cis
diastereoselectivity
is due to the intermediate formation of a trichlorotitanium alkoxide
making possible an easy delivery of chlorine to the carbocation ion from
the same face. The trans isomer is preferred (98% cis) when the switch
is made to a
tin tetrachloride reaction at
room temperature.
The Prins-pinacol reaction is a
cascade reaction of a Prins reaction and a
pinacol rearrangement. The carbonyl group in the reactant in
scheme 8[6] is masked as a dimethyl
acetal and the
hydroxyl group is masked as a
triisopropylsilyl ether (TIPS). With lewis acid
stannic chloride the
oxonium ion
is activated and the pinacol rearrangement of the resulting Prins
intermediate results in ring contraction and referral of the positive
charge to the TIPS ether which eventually forms an
aldehyde group in the final product as a mixture of cis and trans isomers with modest diastereoselectivity.
Uses
The Prins reaction is used in
total synthesis of complex natural products, for example, in a key step of that of the synthesis of exiguolide:
[7]
External links
References
- ^ Condensation of formaldehyde with some unsaturated compounds H. J. Prins, Chemisch Weekblad, 16, 64, 1072, 1510 1919
- ^ Chemical Abstracts 13, 3155 1919
- ^ The Olefin-Aldehyde Condensation. The Prins Reaction. E. Arundale, L. A. Mikeska Chem. Rev.; 1952; 51(3); 505–555. Link
- ^ 4-Phenyl-m-dioxane R. L. Shriner and Philip R. Ruby Organic Syntheses, Coll. Vol. 4, p.786 (1963); Vol. 33, p.72 (1953). Article
- ^ Syn- and Anti-Selective Prins Cyclizations of ,-Unsaturated Ketones to 1,3-Halohydrins with Lewis Acids R. Brandon Miles, Chad E. Davis, and Robert M. Coates J. Org. Chem.; 2006; 71(4) pp 1493 – 1501; Abstract
- ^ Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings Larry E. Overman and Emile J. Velthuisen J. Org. Chem.; 2006; 71(4) pp 1581 – 1587; Abstract
- ^ Total Synthesis of (+)-Exiguolide Min Sang Kwon, Sang Kook Woo, Seong Wook Na, and Eun Lee Angew. Chem. Int. Ed. 2008, 47, 1733–1735 doi:10.1002/anie.200705018
واکنش پرینز
واکنش پرینز
واکنش پرینز (prins) یک واکنش آلی شامل افزایش الکتروفیلی یک آلدهید یا
کتون به یک آلکن یا آلکین با گرفتن نوکلئوفیل است. نتیجه واکنش بستگی به
شرایط واکنش دارد (طرح 1).در حضور آب و اسید پروتیک مانند سولفوریک اسید به
صورت واسطه واکنش و فرمالدهید محصول واکنش یک 3و1- دی ال 3 است.زمانی که
آب حضور ندارد آب زدایی برای تشکیل یک الکل آلیلی 4 اتفاق می افتد. با
مقدار اضافی از فرمالدهید و دمای کم واکنش محصول واکنش یک دی اکسان 5 است.
زمانی که
آب به وسیله استیک اسید جایگزین می شود استرهای مربوطه تشکیل می
شود.
22-Azacholesterol is a novel inhibitor of smoothened that acts through an allosteric mechanism
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