59th Annual Report on Research 2014

We propose the formation of 4a via the mechanism in Scheme 2.  To investigate this path, we previously monitored the photolysis of 1a + 6 via ¹H NMR spectroscopy.  We did not expect to see 3a by NMR due to its microsecond lifetime at room temperature,³ but exploration of the far upfield range (d -0.1 to +0.5 ppm) unfortunately showed no appearance of the cyclopropyl proton of 7-Ph.

Based on the Platz group’s observations of bimolecular trapping of adamantylcarbene (2b),³ we believed the formation of 4b-Ph to result from a mixed carbene “dimerization” of 2b + PhCCl.

Further mechanistic investigations of these two systems involved laser flash photolysis (LFP) kinetics measurements (collaboration with Professor Dasan Thamattoor, Colby College).  To obtain rate data for 1a + 6, we measured the rate of formation of the pyridine ylide of PhCCl at 460 nm at varying [3a].  To vary [3a], we measured k_obs at different [1a].  To connect [3a] with [1a], separately we measured A₃₂₅ of 3a at each concentration of 1a.  The formation of the pyridine ylide of PhCCl in the presence of 3a (from 1a) was independent of [3a]:  k_obs = 4-5 x 10⁷ M^-1s^-1.

LFP was also used to determine the rate constant for the formation of adamantylethylenes 4b-Ph, which we believe is generated by the reaction of adamantylcarbene (2b) with PhCCl.  Partitioning k_obs for the decay of PhCCl at constant [1b] (1.6 x 10⁷ M^-1s^-1) according to the product distribution gives the bimolecular rate constant of 9.6 x 10⁵ M^-1s^-1 for the formation of 4b-Ph, believed to be the first reported rate constant for the reaction of two different carbenes.

Even with the ¹H NMR study of the photolysis of 1a + 6 and the LFP investigations of 1a + 6 and 1b + 6, we did not have conclusive evidence of the proposed mechanisms of formation of 4a-Ph and 4b-Ph.  We have thus begun collaborating with Professor Dean Tantillo (UC Davis) to calculate the potential energy surfaces (PESs) of these two systems:  (a) adamantene 3a + PhCCl and (b) homoadamantene 3b + PhCCl as well as adamantylcarbene 2b + PhCCl.  The Tantillo group has computed the PES for 3a + PhCCl (Figure 1).  The PES shows an intermediate with a structure resembling 7-Ph, but with an elongated C¹-C² distance of 2.35 Å.  Intermediate 7-Ph proceeds over a barrier of <1 kcal/mol to product 4a-Ph (E_rel = -97.0 kcal/mol).  Dynamics trajectories of this system have begun to be computed, where preliminary results show 3a + PhCCl to be under dynamic control.  These results are exciting.  The trajectory calculations are ongoing; we await them with great anticipation, as well as those for the adamantyldiazirine/homoadamantene-PhCCl system.

Figure 1

Although the following does not involve anti-Bredt olefins, the PI’s group has begun to investigate the addition of phenylchlorocarbene to cyclooctynes.  Cyclooctynes have strain energies of 15-20 kcal/mol,¹ which we believe is within the range needed to induce dynamic control of carbene addition.  Our previous computational work of CCl₂ + cyclooctyne showed no barrier to addition and ~100 kcal/mol of energy release, with a possible intervention of a vinylcarbene intermediate on the PES.⁴  We have begun to synthesize the benzannelated cyclooctynes and cyclooctadiene 8-11 (Scheme 3).^5-8  Once obtained, each of 8-11 will be reacted with PhCCl (via photolysis with 6).  Product studies and complementary PES calculations will provide information about the intervention of reaction dynamics.

This report covers the period 9/1/13-8/31/14.  During this time, three Barnard College undergraduates worked on this project, none of whom were funded directly by the PRF.  The reasons why no students were funded by PRF were because two students were funded by individual summer research fellowships which was an honor (HHMI to E. Dalchand, ConEdison to K. Francisco), and the third student (A. Scorese) was funded by the PI’s single-investigator NSF grant nearing expiration.  All three of these students and an additional one will continue in the PI’s lab as seniors, a junior, and a sophomore.  E. Dalchand, S. Tsuno, and C. Buzard presented a poster on this work at the March 2014 ACS National Meeting in Dallas, TX.  The PI presented a poster on this work at the June 2014 Reaction Mechanisms Conference in Davis, CA.  The very promising recent computational results have rightly delayed submission of manuscripts on chlorocarbene additions to each of adamantene and adamantylcarbene.  We project these manuscripts to be submitted by January 2015.  The co-authors on these two manuscripts will include 11 Barnard College undergraduates.  The projected publications will assist substantially in the PI’s efforts towards promotion from associate to full professor.

References cited:

(1)  Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry; University Science: Sausalito, CA, 2006.

(2)  Martella, D. J.; Jones, M., Jr.; Schleyer, P. v. R.; Maier, W. F.  J. Am. Chem. Soc. 1979, 101, 7634-7637.

(3)  Tae, E. L.; Ventre, C.; Zhu, Z.; Likhotvorik, I.; Ford, F.; Tippmann, E.; Platz, M. S.  J. Phys. Chem. A 2001, 105, 10146-10154.

(4)  Mo, X. Y.; Bernard, S. E.; Khrapunovich, M.; Merrer, D. C.  J. Org. Chem. 2008, 73, 8537-8544.

(5)  McKay, C. S.; Moran, J.; Pezacki, J. P.  Chem. Commun. 2010, 46, 931-933.

(6)  Wender, P. A.; Christy, J. P.  J. Am. Chem. Soc. 2007, 129, 13402-13403.

(7)  Wender, P. A.; Lesser, A. B.; Sirois, L. E.  Angew. Chem. Int. Ed. 2012, 51, 2736-2740.

(8)  Wong, H. N. C.; Sondheimer, F.  Tetrahedron 1981, 37, 99-109.