How to Promote Sluggish Electrocyclization of 1,3,5-Hexatrienes by Captodative Substitution

Abstract

Hexatriene electrocyclization, if not disfavored by its harsh reaction conditions, can be highly useful for the synthesis of complex organic molecules. Herein we developed a two-layer ONIOM method which could predict the activation free energy of hexatriene electrocyclization with an accuracy of about 1.0 kcal/mol. Using this carefully benchmarked method, we calculated the activation free energies for a variety of substituted hexatrienes. It was found that extraordinarily rapid electrocyclization could occur for certain patterns of captodative substituted hexatrienes, including 2-acceptor-3-donor hexatrienes, 2-acceptor-5-donor hexatrienes, and 3-acceptor-5-donor hexatrienes. The activation free energies for these systems could be up to 10 kcal/mol lower than that of the unsubstituted hexatriene, and therefore, their electrocyclization could proceed smoothly even at room temperature. The mechanism for the captodative effect on hexatriene electrocyclization could be understood by calculating the affinity between the donor and acceptor group in the reactant state and transition state of the reaction. If the affinity was stronger in the transition state, captodative substitution would produce an extra acceleration effect. It was shown that our theoretical results were in excellent agreement with the experimental data from the recent synthetic studies of hexatriene electrocyclizations. Thus, the theoretical tools developed in the present study could be used to predict not only how to accelerate the hexatriene electrocyclization via substituent manipulation but also under what conditions each particular electrocyclization could be accomplished in the real experiment.

Synthesis of the first representative of dicarbothiacyanine dyes with completely fluorinated polymethine chain

“…In the 19 F NMR spectra of reaction mixture along with minor signals of expected dye base 11 we detected signals of major product that was isolated and identified by X-ray structure analysis as compound 12. Formation of it may be explained by the elecrocyclization [35] of the system of double conjugated bonds with 6-p ē of compound 11 into appropriate cyclohexadiene followed by HF addition (Scheme 6).…”

“…Copper (I) iodide (1.43 g, 7.5 mmol) was added all at once and the solution of stannane 4 (4.87 g, 11.25 mmol) in THF (20 ml) was slowly added over 40 min via syringe. The reaction mixture was maintained at 0 8C for 30 min, then was heated to r.t. for [30][31][32][33][34][35][36][37][38][39][40] …”

Synthesis of cis-vinyltrimethylstannanes and cis-vinylpinacolboronates in a two-step highly regio and stereoselective process

“…An excellent illustration of the need to drive the development of such methodology can be found in the relative under-use of the 6p-electrocyclisation of 1,3-(Z)-5-hexatrienes in strategic synthesis. 1,2 Though not the sole factor, synthetic difficulties in obtaining the requisite 1,3-(Z)-5-hexatrienes in reliable yield and with high stereo-control have certainly limited the utility of such a reaction. To date, cis-vinylstannane and cis-vinylboronate reagents have played a major role in the construction of Z-conjugated systems via transition metal catalyzed cross coupling reactions, i.e., the Stille 3 and Suzuki 4 reactions, respectively.…”

Investigating Direct Access to 2‐Oxospiro[4.5]decanones via 6π‐Electrocyclisation

“…Triene 45, however, cyclised at only 100°C to give 52 in excellent yield, the structure of which was confirmed by X-ray crystallography ( Figure 2). We attribute this reactivity to a lowering of the transition state through a capto-dative effect, [27] induced by the electronwithdrawing effect of the ketone substituent with respect to the β-carbon. Adding further to the utility of this reaction, it was found that a rearrangement of 52 could be driven at higher temperatures (Scheme 6).…”