# Catalytic and Stereoselective C-C-Heteroatom Bond Forming Reactions

> **NIH NIH R35** · BOSTON COLLEGE · 2020 · $389,338

## Abstract

Project Summary
Organic molecules containing chiral α-substituted amines and ethers can be applied to the
synthesis of countless medicinally relevant molecules. These valuable compounds have been
prepared by routes wherein the carbon-based stereogenic center is introduced using “indirect”
diastereo- or enantioselective methods that require the preparation of intermediates that contain
α-substituted leaving groups (e.g., ZnI, halides, triflate, trichloroacetimidates, phosphates); such
approaches lead to lengthy and somewhat inefficient pathways that increase the time required
to secure the desired molecules, substantially increasing the cost of preparing compounds that
are important to human healthcare. There are also the issues of selectivity and substrate scope:
not only must high enantioselectivity and diastereoselectivity be achieved through the use of
readily accessible and cost-effective catalysts, expansion in the scope of compatible substrate
is imperative. Particularly challenging are schemes that lead to chiral α-substituted amines and
ethers through enantio-, diastereo- and regioselective activation of otherwise unreactive α-
amino or α-ethereal C–H bonds. We will develop catalytic processes that combine an
assortment of nucleophiles (enolates, Breslow intermediates, enamines, (hetero)arenes, and
allyl silanes, amines and alcohols), and amines or ethers to generate - in a single operation - a
diastereomically pure and highly enantiomerically enriched product. The resulting compounds
will contain one or two stereogenic centers. Some will carry α- or β-amino carbonyl units as well
as α-(hetero)aryl, α-allyl amino units that are indispensable building blocks in biologically active
molecules. Others will carry α-acyl, β-carbonyl, α-(hetero)aryl, α-amino, α-alkoxy ether moieties.
Various chiral α-substituted amine and ether compounds will thus become readily accessible;
preparation of these entities would otherwise require several operations that can at times
proceed with moderate selectivity. Chiral organoborane catalysts and Lewis acid co-catalysts
will be used to promote the proposed transformations. We will utilize the above strategies to
design pathways that are significantly more efficient than those previously disclosed. We will
develop catalytic processes that can be applied for the late stage functionalization of biologically
important amine and ether molecules. Among the medicinally relevant molecules that will be
subjected to the late stage functionalization are Cymbalta, Sensipar, Methylphenidate,
Metoprolol, Vyvanse and OxyContin, as well as various deoxy sugar molecules.

## Key facts

- **NIH application ID:** 9971555
- **Project number:** 5R35GM128695-03
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Masayuki Wasa
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,338
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971555

## Citation

> US National Institutes of Health, RePORTER application 9971555, Catalytic and Stereoselective C-C-Heteroatom Bond Forming Reactions (5R35GM128695-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971555. Licensed CC0.

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