Erythravine Synthesis Essay
The two synthesis essay questions below are examples of the question type that has been one of the three free-response questions on the AP English Language and Composition Exam as of the May 2007 exam. The synthesis question asks students to synthesize information from a variety of sources to inform their own discussion of a topic. Students are given a 15-minute reading period to accommodate the additional reading required for the question.
Below is a sample synthesis essay question, sample scoring guidelines, comments from the Chief Reader about the sample student essays, seven sample student responses, and scoring commentary for each sample.
Approximately 300 AP English Language and Composition students from eight schools in New York, Maine, Texas, Tennessee, Washington, Florida, and New Mexico wrote responses to this synthesis topic. Students from these schools were given a 15-minute reading period followed by a 40-minute writing period in which to complete the sample synthesis assignment.
An additional sample synthesis essay question is provided here.
Adjacent to the heteroatom
There are many examples of the synthesis of tetrahydropyrans which are based on the cyclization of 1,5-diols and compounds which can provide a similar electrophilic site for ring closure.
Pentan-1,5-diols can be quantitatively cyclized to the pyran in the presence of BuSnCl3 in a simple experimental method 〈88G483〉.
Chiral tetrahydropyrans result from intramolecular trapping of the cations derived from iron tricarbonyl-butadiene complexes. Separation of stereoisomers and decomplexation are facile (Equation (41)) 〈91SL895〉.
Alkylalkoxysilanes condense with aldehydes to give cis-2,4,6-trisubstituted tetrahydropyrans. The Lewis acid catalyzed process takes place in two stages and it is possible to use different aldehydes for each step, producing unsymmetrically substituted pyrans. The 4-substituent is derived from the catalyst (Scheme 57) 〈89JOC5768〉.
The triols (80) react with trialkyl orthoesters under acid conditions to form the 2-substituted tetrahydropyran by way of a cyclic orthoester (Scheme 58) 〈93H(35)665〉.
The stereochemistry of the tetrahydropyrans produced by reductive cleavage of bicyclic acetals can be controlled by the choice of reagent. Thus, DIBAL-H gives the trans isomer (81), whereas a mixture of TiCl4 and triethylsilane affords mainly the cis compound (82) (Equation (42)) 〈90T4595〉.
Several instances of halolactonization have been reported 〈90JOC283, 93SL927, 94CC763, 95CC989〉 including its use in the formation of an 11-oxasteroid 〈89H(28)905〉.
1,5-Diols are oxidatively cyclized to tetrahydropyran-2-ols using environmentally friendly reagents 〈94TL8477〉, whilst the oxidative cleavage of 1,2-diols features in another tetrahydropyran synthesis 〈95JCS(P1)2989〉. Tetrahydropyran-2-ols are also available from diketene and β-hydroxy-aldehydes 〈94T2047〉. δ-Silyloxy 〈89CL259〉 and δ-bromo 〈89TL6571〉 carbonyl compounds are alternative precursors. Polycyclic tetrahydropyrans can also be obtained using this approach 〈93TL4105, 94TL97〉.
Tetrahydropyran syntheses based on cyclization of pent-4-en-1-ols are quite common and feature in syntheses of natural products 〈93T5979, 93TL5739, 94TL323〉. The cyclization can be assisted by sulfenylation 〈95TL1909〉, selenation 〈90TL6535, 92LA261, 94T139, 95JOC4660, 95SL855〉, iodination 〈94CC1469, 95SL663〉, and mercuriation 〈90JA7407, 94CC767, 94T139〉. Acid catalysis 〈87CC1718, 88TL681, 89JOC4723, 92H(33)51, 94SL594, 95TL2453〉, Lewis acid catalysis 〈89CRC29〉, and basic conditions 〈92TL2399, 93SC1009, 93TL111〉 are also effective.
Intramolecular palladium catalyzed cyclization of alkenols allows additional functionalization of the tetrahydropyran through the trapping of an intermediate palladium species. Thus, methoxy-carbonylation 〈84JA1496, 89JOC4485〉, vinylation 〈93TL7205〉, and hydride elimination 〈89JOC4483〉 lead to 2-functionalized tetrahydropyrans (Scheme 59).
The palladium-catalyzed cyclization of the dienols (83) involves a 1,4-oxidation and offers a route to fused tetrahydropyranols in a highly stereoselective manner which can be influenced by added nucleophile (Equation (43)) 〈92JA6374, 95TL5397〉. When the side chain is attached to the 1-position of the diene moiety, spirocyclization occurs. Added nucleophile can be incorporated into the product 〈91JOC2274〉.
A significant variation on the alkenol theme is the stereo- and regio- selective ring opening of hydroxyepoxides (Equation (44)) 〈89JA5330〉. 5-exo-Cyclization competes with the 6-endo mode but the latter is dominant when an electron-rich unsaturated function is present on the epoxide carbon atom remote from the hydroxy group. Similar controls apply to the next higher homologue of the hydroxy epoxides 〈89JA5335〉.
Other examples using the epoxide route to tetrahydropyrans include 〈90TL4747, 92JOC50, 92TL4349, 93JA3558, 93TL5421, 93TL6925, 94TL2179〉. Epoxides feature in a one-pot synthesis of 3-methylene-tetrahydropyrans in which the initial epoxide ring-opened product arising from attack by a Grignard reagent is cyclized by Pd(0) (Scheme 60) 〈92T9901〉.
A 1,5-diene can be converted into a substituted tetrahydropyran by conversion into the diepoxide. Subsequent acidic hydrolysis is accompanied by cyclization. It is suggested that one epoxide is converted to the diol and the other undergoes intramolecular ring opening 〈89SC1233〉.
6-exo-Cyclization of the diol (84) proceeds via the episulfonium ion and involves attack at the more substituted carbon atom of the three-membered ring. Cyclization gives the anti product and this allows control of ring size when alternative nucleophiles are incorporated into the molecule, as in (85) (Scheme 61) 〈92TL539〉.
Cobalt complexes derived from alkynic epoxides undergo a Lewis acid catalysed 6-endo cyclization in which the configuration of the substrate is retained in the tetrahydropyran (Scheme 62) 〈94TL2179〉. In the absence of the catalyst, the mode of cyclization is determined by the terminal substituent on the alkyne moiety. Electron-releasing groups favor 6-endo cyclization over the 5-exo mode. Furthermore, inversion of configuration at the propynyl position is noted 〈94TL2183〉.
The cyclization of 1,5-hydroxyketones has been extensively used to prepare tetrahydropyranols and, notably, spiroketals and consequently this methodology has been used in the synthesis of a number of naturally occurring molecules 〈89T5935, 95TA397〉.