1.). In scheme 3 cyclopropane 3 is acting as: a.) nucleophile b.) solvent c.) ac
ID: 1036936 • Letter: 1
Question
1.). In scheme 3 cyclopropane 3 is acting as: a.) nucleophile b.) solvent c.) acid d.) catalyst
In scheme 4 cyclopropane 11w is acting as: a. ) nucleophile b.) solvent c.)catalyst d.) acid
2.) Consider the LiET3BH reduction I and the organometallic addition to 3. Why is the ketone selectively attacked instead of the ester?
iPad? 1:08 PM * 46%. ) 6a (14%) 4o R 4-OMe 4p R H 4q R 4-CI ??? 4s While ABLs have been generated from the reactions of vinyl cyclopropanes with substituted benzaldehydes in the presence of DABCO, no examples of their synthesis from cyclopropyl carbinols have been reported. Intrigued by the formation of 6a, we were particularly interested in discerning the factors that govern the chemoselectivity of the reaction (formation of 5 and/or 6) and how they could be rationalized in terms of substituent effects. We envisioned that this knowledge would contribute to determining the conditions for selective ABL formation, establishing cyclopropyl carbinols 4 as a useful common precursor to multiple different, yet desirable, core structures. This type of approach represents one of the hallmarks of diversity-oriented synthesis.20 Toward that end, we disclose our studies on the Bi(OTf)3-calyzed, ring-opening cyclization of cyclopropyl carbinols 4 to form ABLs 6 and show how the dehydrative, ring-opening cyclization is dependent upon the electronic nature of the substituents on both the carbinol and the cyclopropane ring (Scheme 2) R OH 19 4x R Me Instead, 4w was synthesized using Nishii's Reformatsky approach (Scheme 4)1-Dibromocyclopropane 10w Scheme 4. Reformatsky Approach to Carbinol 4w 1) n-BuLi then Zn ??? Me 2) K2CO3 46% (over two Mel 10w (prepared in one step from styrene) steps) RESULTS AND DISCUSSION Synthesis of Carbinols 4. Carbinols 4a-v, 4x, and 4y were (prepared from the reaction of styrene with CHBr3, aq prepared using a three-step sequence from the corresponding NaOH, and catalytic BnEt,NBr) was treated with n-BuLi and B-ketoesters 1. Diazo transfer followed by Rh(II)-catalyzed quenched with dry ice (CO.). Following workup, the crude acid was converted to the ester 11w using K2CO3 and Mel in (D-A) cyclopropanes 3, LiEt3BH reduction generated 46% yield over the two steps. Lastly, formation of the secondary (2°) carbinols 4a-v. Tertiary (3°) carbinols 4x Reformatsky reagent and reaction with 3-pentanone gave cases, the carbinols are prepared and used as cyclopropanation with various olefins gave donor-acceptor and 4y were obtained upon addition of methyl- or phenyl lithium to the D-A cyclopropane, respectively (Scheme 3) carbinol 4w. In all mixtures of diastereomers. For the preparation of trialkyl 3° carbinol 4w, the previously discussed sequence failed to provide the desired product. of ABL 6a in the previous report (Scheme 1), carbinol 4a was Reaction Optimization. Given the benchmark formation 15 Scheme 2. Bi(OTf)3-Catalyzed Ring-Opening Cyclization of Cyclopropyl Carbinols R5 OMe cat. Bi(OT)3Explanation / Answer
1) cyclopropane 3 is acting as electrophile
cyclopropane 4w is acting as nucleophile
2) carbonyl group is much more reactive than ester towards nucleophilic addition of the hydride from the boron reagent as it is more hard center compared to ester
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