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. 2021 Oct 6;12(41):13902-13908.
doi: 10.1039/d1sc04082k. eCollection 2021 Oct 27.

Silicon as a powerful control element in HDDA chemistry: redirection of innate cyclization preferences, functionalizable tethers, and formal bimolecular HDDA reactions

Mandy Lynn  1 , Merrick Pierson Smela  1 , Thomas R Hoye  1
Affiliations

Silicon as a powerful control element in HDDA chemistry: redirection of innate cyclization preferences, functionalizable tethers, and formal bimolecular HDDA reactions

Mandy Lynn et al. Chem Sci. .

Abstract

The 1,3-diyne and diynophile in hexadehydro-Diels-Alder (HDDA) reaction substrates are typically tethered by linker units that consist of C, O, N, and/or S atoms. We describe here a new class of polyynes based on silicon-containing tethers that can be disposed of and/or functionalized subsequent to the HDDA reaction. The cyclizations are efficient, and the resulting benzoxasiloles are amenable to protodesilylation, halogenation, oxygenation, and arylation reactions. The presence of the silicon atom can also override the innate mode of cyclization in some cases, an outcome attributable to a β-silyl effect on the structure of intermediate diradicals. Overall, this strategy equates formally to an otherwise unknown, bimolecular HDDA reaction and expands the versatility of this body of aryne chemistry.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. (a) Previous studies of HDDA cascade reactions using erasable sulfur-based linkers. (b) In this report we disclose formal bimolecular HDDA reactions using disposable and/or functionalizable silicon linkers.
Fig. 2
Fig. 2. Preliminary results demonstrating that silicon-tethered HDDA cascades are feasible.
Fig. 3
Fig. 3. Preparation of tetraynes 12a–d. (PMP = p-methoxyphenyl).
Fig. 4
Fig. 4. (a) Exclusive formation of 14a (via a single benzyne) from the tetrayne substrate 12a. (b) DFT calculations of the relative free energies (ΔG) of species on the potential energy surface for the reaction of the slightly simplified, model tetrayne 15a (at 413 K) [SMD(chloroform)/(U)B3LYP-D3BJ/6-311+G(d,p)//(U)M062X/6-311+G(d,p)].
Fig. 5
Fig. 5. Products 14 from HDDA cascades using alkoxysilane-tethered tetraynes/triynes 12 and various trapping agents. (TPCPD = tetraphenylcyclopentadienone).
Fig. 6
Fig. 6. Synthesis of naphthalene derivatives 17via deoxygenation of benzoxanorbornadiene derivatives.
Fig. 7
Fig. 7. Iodination and bromination of the C–Si bond (with concomitant cleavage of the tether).
Fig. 8
Fig. 8. Synthetically useful transformations of benzoxasiloles (with concomitant cleavage of the tether).
Fig. 9
Fig. 9. Triyne substrates 12f and 12g show complementary modes of ring-closing selectivity, dictated by the relative position of diyne and monoyne relative to the silicon atom. (a) The first (12f) proceeds through HDDA cyclization. (b) The second (12g) proceeds through TDDA cyclization. In each case (as with 12a), the alkyne carbon beta to the silicon atom (•) participated in the closure to the new six-membered ring.
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