# Reinforced Reasoning for End-to-End Retrosynthetic Planning

arXiv: https://arxiv.org/abs/2603.29723 · HTML: https://mlsanity.com/paper/2603.29723/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 51 of its 91 references that are in the map.
- First posted on arXiv 31 Mar 2026.

## Builds on (most cited first, 30 of 51)

- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Llama 2: Open Foundation and Fine-Tuned Chat Models](https://mlsanity.com/paper/2307.09288/) (2023)
- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Self-Consistency Improves Chain of Thought Reasoning in Language Models](https://mlsanity.com/paper/2203.11171/) (2022)
- [DAPO: An Open-Source LLM Reinforcement Learning System at Scale](https://mlsanity.com/paper/2503.14476/) (2025)
- [Distilling Step-by-Step! Outperforming Larger Language Models with Less Training Data and Smaller Model Sizes](https://mlsanity.com/paper/2305.02301/) (2023)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [On the Planning Abilities of Large Language Models : A Critical Investigation](https://mlsanity.com/paper/2305.15771/) (2023)
- [Reinforcement Learning with Verifiable Rewards Implicitly Incentivizes Correct Reasoning in Base LLMs](https://mlsanity.com/paper/2506.14245/) (2025)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [Large-Scale Chemical Language Representations Capture Molecular Structure and Properties](https://mlsanity.com/paper/2106.09553/) (2021)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)
- [Translation between Molecules and Natural Language](https://mlsanity.com/paper/2204.11817/) (2022)
- [Thinkless: LLM Learns When to Think](https://mlsanity.com/paper/2505.13379/) (2025)
- [ChemLLM: A Chemical Large Language Model](https://mlsanity.com/paper/2402.06852/) (2024)
- [Retrosynthesis Prediction with Conditional Graph Logic Network](https://mlsanity.com/paper/2001.01408/) (2020)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [Retrosynthetic reaction prediction using neural sequence-to-sequence models](https://mlsanity.com/paper/1706.01643/) (2017)
- [A Graph to Graphs Framework for Retrosynthesis Prediction](https://mlsanity.com/paper/2003.12725/) (2020)
- [Retro*: Learning Retrosynthetic Planning with Neural Guided A* Search](https://mlsanity.com/paper/2006.15820/) (2020)
- [The Synthesizability of Molecules Proposed by Generative Models](https://mlsanity.com/paper/2002.07007/) (2020)
- [Permutation invariant graph-to-sequence model for template-free retrosynthesis and reaction prediction](https://mlsanity.com/paper/2110.09681/) (2021)
- [Learning Graph Models for Retrosynthesis Prediction](https://mlsanity.com/paper/2006.07038/) (2020)
- [SMILES Enumeration as Data Augmentation for Neural Network Modeling of Molecules](https://mlsanity.com/paper/1703.07076/) (2017)
- [Developing ChemDFM as a large language foundation model for chemistry](https://mlsanity.com/paper/2401.14818/) (2024)
- [Root-aligned SMILES: A Tight Representation for Chemical Reaction Prediction](https://mlsanity.com/paper/2203.11444/) (2022)
- [Barking up the right tree: an approach to search over molecule synthesis DAGs](https://mlsanity.com/paper/2012.11522/) (2020)

## Abstract (arXiv)

Retrosynthetic planning is a fundamental task in organic chemistry, yet remains challenging due to its combinatorial complexity. To address this, conventional approaches typically rely on hybrid frameworks that combine single-step predictions with external search heuristics, inevitably fracturing the logical coherence between local molecular transformations and global planning objectives. To bridge this gap and embed sophisticated strategic foresight directly into the model's chemical reasoning, we introduce ReTriP, an end-to-end generative framework that reformulates retrosynthesis as a direct Chain-of-Thought reasoning task. We establish a path-coherent molecular representation and employ a progressive training curriculum that transitions from reasoning distillation to reinforcement learning with verifiable rewards, effectively aligning stepwise generation with practical route utility. Empirical evaluation on RetroBench demonstrates that ReTriP achieves state-of-the-art performance, exhibiting superior robustness in long-horizon planning compared to hybrid baselines.