99 Deaminative Ring Contractions for the Synthesis of 1 AZA-[n]Helicenes

Faculty Mentor: Andrew Roberts (Chemistry, University of Utah)

Introduction

Helicenes are polycyclic aromatic compounds containing more than three consecutive, ortho– condensed rings. They are valued in materials science applications for their reciprocal optical activity (due to helically chiral enantiomers) in conjunction with their strong fluorescence. Combined, these properties enable the production of chiral materials that emit circularly polarized light ((–)-M and (+)- P forms, Fig. 1a).^[1] Additionally, extended helicenes (more than five rings) also have promising utilizations in electronics, with the use of cellulose-based biosensors for medical diagnosis being a notable example.^[2]

Despite aza[n]helicenes having practical uses, they are underdeveloped due to their difficult and costly synthesis routes that require multi-step sequences using advanced building blocks. Aza[n]helicenes with six or more consecutive ortho-fused rings have been particularly understudied due to their size and complexity. Moreover, the building blocks needed to prepare them are difficult to make. The deaminative ring contraction for the synthesis of 1-aza[7]helicenes is an advanced method developed in the Roberts group. Currently, a generic build-cyclize-contract strategy is utilized to convert commercially available secondary amines polycyclic (hetero)aromatics (e.g. benzo[h]quinoline and phenanthrenes) Fig. 1b. The aim of this project utilizes the build-cyclize- contract strategy to successfully synthesize 1-aza[7]helicene. The success of my efforts could enable access to larger helicenes, including #-aza[8] and #-aza[9]helicene variants.

Background

Previously, The Roberts group developed the build-cyclize-contract strategy for substituted benzo[h]quinolines and phenanthrenes. Starting from commercially available building blocks, a secondary amine is able to undergo a reductive amination with a substituted benzaldehyde or an alkylation with a substituted benzyl bromide (formed in situ). Next, a Ni-catalyzed electrophilic cyclization forms the biaryl-linked dihydroazepine intermediate. Finally, a deaminative contraction affords the C=C bond via [1,2]-Stevens rearrangement, Hofmann-type elimination cascade. Turning the attention to larger, ortho-fused ring systems, #-aza[5]helicenes and #-aza[6]helicenes were easily accessed with high yields and efficiency via the build, cyclize, contract strategy.^[3][4] Taking motivation from the [5] and [6]helicenes, we set out to access 1-aza[7]helicene.

Results

Starting from a commercially available secondary amine, an alkylation proceeds in excellent yield with naphthylbromide (formed in situ) to afford tertiary amine 3 (Fig. 2). Next, the brominated tertiary amine 3 undergoes a Ni-promoted cyclization to form biaryl-linked dihydroazepine 4. The azepine then undergoes a deaminative ring contraction via a [1,2]-Stevens rearrangement, Hofmann elimination-type cascade, giving the desired C=C bond and excising dimethylamine yielding 1- aza[4]helicene 5. With 1-aza[4]helicene (5) obtained, a Sanford bromination is performed,^[5] giving an aryl bromide in the C12 position 6. The moderate yield of this reaction is most likely attributed to the sensitivity of this reaction to air while being at high pressure and temperatures.

Next, 6 undergoes a benzylic bromination in good yield with N-bromosuccinimide and benzoyl peroxide accessing 7. Herein the build, cyclize, contract happens sequentially to afford 9, 10, and 1- aza[7]helicene (11). Secondary naphthylamine 8 easily accessed in one step from the aldehyde. The cyclization was met with an unexpected lower yield. Upon further studies, we attentively attribute this low yield due to steric hindrance during catalysis. Finally, the deaminative contraction proceeded once optimized conditions were developed.

Conclusion

Until recently, larger helicenes were not easily accessed from current syntheses. This can be due to their lengthy synthesis or costly starting materials. The success of the total synthesis for the 1- aza[7]helicenes gives promise to access even larger helicenes via the build-cyclize-contract strategy via the 1-aza[4]helicene building block. Motivated by the general access of 1-aza[7]helicene, we aim to access 1,18-diaza[7]helicene, 1-aza[8]helicene, 1,20-diaza[8]helicene, 1-aza[9]helicene, and 1,22- diaza[9]helicene (Fig. 3).