Highly Diastereoselective Multicomponent Cascade Reactions: Efficient Synthesis of Functionalized 1-Indanols

Jun Jiang, Xiaoyu Guan, Shunying Liu, Baiyan Ren, Xiaochu Ma, Xin Guo, Fengping Lv, Xiang Wu, and Wenhao Hu
Angew. Chem. Int. Ed.
DOI: 10.1002/anie.201208391

hu1

Wenhao Hu has been reporting remarkable reactions of transition metal-generated oxonium ylides for some time now. Oxonium ylides formed from alcohol insertion into carbenoids tend to undergo rapid 1,2-proton shift to give ethers (path A). However, Hu and coworkers report reactions where this process is delayed long enough for the ylide to react as a carbon nucleophile with electrophilic coupling partners (path B).

hu2

Recently, these oxonium ylides have been shown to undergo a cascade reaction with a dielectrophilic compound containing an unsaturated ester and an aldehyde. The ylide adds selectively to the Michael acceptor, which is followed by intramolecular aldol-type addition to the aldehyde to generate a complex indanyl adduct. The product is formed as a single diastereoisomer.

hu3

The group also report an asymmetric variant of the reaction using a chrial auxiliary on the diazo substrate.

Subsequent studies into the reaction attempted an intermolecular multicomponent cascade. Unfortunately, the product of 1,2-proton shift was preferred and no 4-component products were observed. More interestingly, the product of addition of the ylide into the unsaturated ester was only observed in 13% yield. This suggests that trapping of the oxonium ylide by the unsaturated ester in the dielectrophilic compound above is synergistically promoted by the presence of the aldehyde and subsequent aldol cyclisation.

hu4

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s