Prins type cyclization reaction

Tetrahydropyrans hydroxylated at the 4-position have good synthetic value [113]. Although many synthetic methods have been reported [17-23,114,115], the search for potential alternate approaches and the development of eco-friendly and high-yielding reactions resulted in the development of a method that poses less problems for the environment. Synthesis of tetrahydropyranol derivatives can be achieved through the Prins-type cyclization reaction of homoallylic alcohols with aldehydes using bismuth triflate as catalyst in [bmim]PF6 solvent system [108] (Fig. 22). 

Yang, J., Viswanathan, G. S., Li, C.-J. Highly effective synthesis of 4-halotetrahydropyrans via a highly diastereoselective in situ Prins-type cyclization reaction. Tetrahedron Lett. 1999,40,1627-1630. 

Prins-type cyclization reactions in natural product synthesis 12COC1277, 13EJ01193. 

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

Formaldehyde can be coupled to an alkene in the presence of an acid to give a diol (152) or a 1,3-dioxane derivative (154) in what is known as the Prins reaction. l Allylic alcohols such as 153 can also be produced in this reaction. Camphene (155) reacted with formaldehyde and acid to give a 1 1 mixture of allylic alcohol 156 and the acetate 157, in 94% yield. Scandium tiiflate has been used to prepare tetrahydropyran-4-ol derivatives from aldehydes and homoallylic alcohols via a Prins-type cyclization. 3... 

Barluenga J, Fernandez A, Di6guez A, Rodriguez F, Fananas FJ (2009) Gold- or platinum-catalyzed cascade processes of alkynol derivatives involving hydroalkoxylation reactions followed by Prins-type cyclizations. Chem-Eur J 15 11660-11667. doi 10.1002/ chem.200900856... 

Barluenga et al. [29] reported a tandem cyclization/Prins type of reaction of 1-en-8-yn-4-ols. As shown in Scheme 4.16, hydroaUcoxylation of the C—C triple bond is the fist step. The enol intermediate 62 thus formed could be protonated to form the oxocarbenium species 63. With the C—C double bond positioned ideally for a Prins type of cyclization, such a process indeed ensues, resulting in the formation of the synthetically useful bicyclic bridged ether 61 in an excellent yield. 

Moreover, in a subsequent paper, a reaction based on a gold- or platinum-catalyzed tandem process that involves an intramolecular hydroalkoxylation of a triple bond followed by a Prins-type cyclization has been reported for the synthesis of [3.3.1]bicyclic compounds starting from easily available alkynol derivatives [152] (Scheme 89). 

Moreover, spiroketals are produced from tandem hydroalkoxylation of 4-alkynols (Scheme 15) [130]. Starting from diynediols, bis-spiroketals are obtained using Au (I) as catalysts [131]. Furthermore, Barluenga et al. reported the formation of spirocychc compounds in a tandem alkyne hydroalkoxylation [4 -1- 2] cycloaddition reaction [132, 133], together with a tandem intramolecular hydroalkoxylation of a triple bond followed by a Prins-type cyclization [129]. 

Scheme 1). Introduction of a jt bond into the molecular structure of 1 furnishes homoallylic amine 2 and satisfies the structural prerequisite for an aza-Prins transform.4 Thus, disconnection of the bond between C-2 and C-3 affords intermediate 3 as a viable precursor. In the forward sense, a cation ji-type cyclization, or aza-Prins reaction, could achieve the formation of the C2-C3 bond and complete the assembly of the complex pentacyclic skeleton of the target molecule (1). Reduction of the residual n bond in 2, hydro-genolysis of the benzyl ether, and adjustment of the oxidation state at the side-chain terminus would then complete the synthesis of 1. 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

A 1-endo reaction forming a Prins-type product has been described43. The cyclization of acid chloride 19 leads to a mixture of the chlorides 20 a consecutive dehydrohalogenation results in the cycloheptenone 21 in about 67% overall yield. 

Eight- and nine-membered cyclic ethers are also generated via type-III reactions by treating the 5-hexen-l-ol acetals with Lewis acids. 8-endo Cyclization of 5-hexenyl methoxyethoxymethyl ether in the presence of two equivalents of tin(IV) chloride forms a 2 1 mixture of chlorinated and unsaturated 1 -oxycyclooctanes 11 and 1232. Vinylsilane undergoes an 8-endo Prins cyclization. After O-desilylation, oxocene 13, which is used as a precursor in a laurenyne synthesis, is obtained in 37% yield33. 

Finally, Huang and Panek utilized a Prins-type reaction between a crotylsilane and an aldehyde in their total synthesis of callipeltoside A (28).21 22 In the presence of TfOH, crotylsilane 25 and aldehyde 26 underwent mixed acetal formation and subsequent Prins cyclization to generate dihydropyran 27 in 87% yield as a single diastereomer. This intermediate was carried forward to complete a total synthesis of 28.22... 

This reaction was first reported by Kriewitz in 1899. It is the condensation between formaldehyde and olefins to form unsaturated primary alcohols under conditions of high temperature (e.g., 170°C). In this reaction, water or acetic acid is usually applied as the solvent, and an acid is added as a catalyst, such as sulfuric acid. Under these conditions, formaldehyde and some ketones function as an enophile. The double bond in the new unsaturated alcohol is adjacent to its original position in the starting olefin," with the exception of camphene, which gives an allylic alcohol. For the acylic olefins in this condensation, the isobutylene-type olefins are much more reactive than the monosubstituted olefins or 1,2-disubstituted olefins. The further extension of this reaction involving an intramolecular condensation of an a-alkoxycarbenium ion with a double bond to form a hydropyran derivative is known as the Prins-Kriewitz cyclization. ... 

Tosylhydrazones such as (149), containing a suitably disposed olefinic group, cyclize to bicyclic azo-compounds [e.g. (150)] on treatment with boron trifluoride etherate. The allyl silanes (151) and (152) each undergo a highly stereoselective Prins-type reaction on treatment with trifluoroacetic acid, whereas other acid catalysts give mixtures. ... 

Cyclization via Prins-Type Reactions The intramolecular Prins reaction has been recognized as a powerful method to assemble six- and seven-membered rings from homoallylic alcohols and simple aldehydes under acid catalysis [28]. However, the competing 2-oxo-Cope rearrangement prior to cyclization could lead to a product with partial or total racemization when enantiomerieally enriched secondary alcohols are used [29]. Increasing the nueleophilicity of the alkene reagent... 

Prins-type Reaction. A versatile method for the synthesis of 4-substituted 6-methyl-3-oxabicyclo[3.3.1]non-6-ene-l-methanol derivatives has been developed using Prins-type cycliza-tion reaction between aldehydes and 0-protected/unprotected cyclohex-3-ene-1,1-dimethanol. The optimized reaction conditions used Hf(OTf)4 and various substrates including functionalized benzaldehydes and heteroaromatic carbaldehydes, to afford the cyclization products in high yields (eq 7). Among various metal triflates tested, Hf(OTf)4 provided the best results. 

Catalysis of Intramolecular Sakurai Reactions. Et AICI2 has been extensively used as a catalyst for intramolecular Sakurai additions. Enones (eqs 12 and 13) have been most extensively explored. Different products are often obtained with fluoride or Lewis acid catalysis. EtAlCl2 is the Lewis acid used most often although TiCLi and BF3 have also been used. EtAlCl2 also catalyzes intramolecular Sakurai reactions with ketones and other electrophiles. The cyclization of electrophilic centers onto alkylstannanes and Prins-type additions to vinylsilanes are also catalyzed by EtAlCl2. 

The silyl-modified Prins reaction and the silyl-modified Sakurai reaction are common methods employed for dihydropyran (and tetrahydropyran) synthesis, and are in fact the same reaction. For the sake of clarity, the term silyl-Prins cyclization is adopted herein. A review of the use of silicon containing compounds in reactions of this type is available <1995CRV1375>. 

---