عنوان

Chiral Phosphoric Acid-Catalyzed Mannich Reactions of Latent Nucleophiles with Acyl Imines

شماره

TLpq2316417211

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

Chiral Phosphoric Acid-Catalyzed Mannich Reactions of Latent Nucleophiles with Acyl Imines

نام عام مواد

[Thesis]

نام نخستين پديدآور

Escobar Medina, Randolph Antonio

نام ساير پديدآوران

Schaus, Scott E.

نام ناشر، پخش کننده و غيره

Boston University

تاریخ نشرو بخش و غیره

2019

نام خاص و کميت اثر

236

جزئيات پايان نامه و نوع درجه آن

Ph.D.

کسي که مدرک را اعطا کرده

Boston University

امتياز متن

2019

متن يادداشت

Chiral phosphoric acids were used to activate the acyl imine to facilitate a highly enantioselective addition of an enecarbamate to afford the 1,3-diamine Mannich adduct. An extensive catalyst screen found that the sterically hindered 9-phenanthryl binaphthyl phosphoric acid was the optimal catalyst for the parent reaction yielding the product in 98% yield and a 96:04 e.r. In order to further optimize the reaction, a series of mechanistic studies were performed, including NMR and ReactIR experiments to understand the reaction in situ. These experiments led to the discovery of a hemiaminal ether intermediate. It was ultimately proposed that the carbonyl moiety present in the enecarbamate does a nucleophilic addition onto the activated acyl imine to yield the chiral hemiaminal ether which then undergoes rearrangement to form the expected product. After additional mechanistic studies, it was observed that the initial formation of the intermediate is the enantiodetermining step and that stereoselective intramolecular rearrangement occurs to form the 1,3-diamine Mannich product. Upon gaining insight from these experiments, optimal conditions were achieved using the parent reaction to yield the Mannich product in a 98% yield and 98:02 e.r. After reaction optimization, the substrate scope was then investigated. Emphasis was placed on the protecting groups of the acyl imines. Following a 2-dimensional screen of catalyst vs protecting group, an optimal catalyst was found for each protecting group. Additionally, other enecarbamates and imines were attempted affording a total of 32 examples with high enantioselectivity and yields. Reductions were then performed on the Mannich product to gain access to the appropriate chiral 1,3-diamine. This methodology represents a new route to make chiral 1,3-diamines through the formation of a chiral hemiaminal ether. This reactivity has been expanded to include syntheses of other diamines such as 1,2-diamines. Preliminary results show that when using glycinate derivatives with acyl imines, the formation of a hemiaminal ether is observed which then undergoes rearrangement to form the chiral 1,2-diamine directly.

موضوع مستند نشده

Chemistry

موضوع مستند نشده

Organic chemistry

مستند نام اشخاص تاييد نشده

Escobar Medina, Randolph Antonio

مستند نام اشخاص تاييد نشده

Schaus, Scott E.

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y