# Phosphine-Catalyzed Annulations and their Applications

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $355,809

## Abstract

PROJECT SUMMARY
The overarching goal of this project is to develop new catalysts and reactions to empower the chemical synthesis
of biologically active natural product targets and pharmaceuticals. In particular, we formulate a rationale for
designing strained and bridged bicyclic phosphine oxides that can be readily reduced back to phosphines after
the phosphine oxides are formed in situ. A new bridged [2.2.1] bicyclic phosphine oxide has already displayed
reactivity, in both catalytic Wittig and Staudinger reactions, superior to that of the best alternatives known today.
Experimental and theoretical investigations have predicted that the proposed [2.1.1] bicyclic phosphine oxides
would be even more reactive. Considering the ubiquity of reactions driven by the formation of phosphine oxides
(e.g., Staudinger, Wittig, Mitsunobu, and Appel reactions), and their environmental consequences, our proposed
research should have significant impact on organic synthesis. Our inspiration for the bridged [2.2.1] bicyclic
phosphine oxide originated from the trans-4-hydroxy-L-proline (Hyp)–derived chiral phosphines we developed
during the last funding period. Building on the greater faculty of the [2.2.1] bicyclic phosphine oxide, we will apply
the Hyp-derived 2-aza-5-phosphabicyclo[2.2.1]heptanes to catalytic asymmetric Staudinger, Wittig, Mitsunobu,
and Appel reactions. These chiral phosphines have already exhibited tremendous potential in facilitating
enantioselective Mitsunobu and Appel reactions and the first successful example of a catalytic asymmetric
Staudinger/aza-Wittig reaction. We will also create new bridged [2.2.1] bicyclic chiral phosphines from carvone.
Carvone-derived P-chiral phosphines should be versatile catalysts because both enantiomers of carvone are
naturally abundant and, therefore, inexpensive. Capitalizing on the capacity of phosphines to serve as both
organic catalysts and ligands on homogeneous transition metal catalysts, we propose to develop a tandem
Michael-Heck reaction of alkenyl halides and activated acetylenes for the assembly of 5- and 6-membered
carbo- and heterocycles. One particular Michael-Heck process employing iodoalcohols is a powerful tool for
assembling furans of almost any substitution pattern and provides access to several structurally disparate
furanosesquiterpenoid natural products. We have already made 10 different Hyp-derived chiral phosphines
commercially available through Sigma–Aldrich and will collaborate with them again to make our phosphine
oxides and chiral phosphines available to the scientific community. Many research groups have already used
Hyp-derived phosphines in a variety of catalysis reactions. We anticipate that the proposed research will have a
similar significant impact on chemical synthesis. Collectively, the catalysts and reactions developed in this
application will allow the enantioselective preparation of medicinally significant pharmaceuticals and natural
product targets.

## Key facts

- **NIH application ID:** 9983001
- **Project number:** 5R01GM071779-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** OHYUN KWON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,809
- **Award type:** 5
- **Project period:** 2006-05-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983001

## Citation

> US National Institutes of Health, RePORTER application 9983001, Phosphine-Catalyzed Annulations and their Applications (5R01GM071779-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983001. Licensed CC0.

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