. Author manuscript; available in PMC: 2018 Dec 13.

Published in final edited form as: J Am Chem Soc. 2017 Nov 27;139(49):18107–18114. doi: 10.1021/jacs.7b11197

Table 2.

Optimization of Peptide Sequence and Length^a


Entry	Ligand	i	i+1	i+2	i+3	i+4	3 % Remaining^b	4a %Yield^b	6a % Yield^b	er^c
1	L1	TMG-Asp	D-Pro	Aib-OLi	-	-	16	65	13	94:6
2	L2	TMG-Asp	D-Pro	Cle-OLi	-	-	23	62	8	93:7
3	L3	TMG-Asp	D-Pro	D-Ala-OLi	-	-	19	61	11	92:8
4	L4	TMG-Asp	D-Pro	Gly-OLi	-	-	22	62	9	92:8
5	L5	TMG-Asp	D-Pro	Acpc-OLi	-	-	27	58	6	93:7
6	L6	TMG-Asp	D-Pro	Ala-OLi	-	-	21	60	8	93:7
7	L7	TMG-Asp	D-Pro	Aib-OMe	-	-	6	52	18	95:5
8	L8	TMG-Asp	D-Pro	Aib-NHMe	-	-	9	59	20	95:5
9	L9	TMG-Asp	D-Pro-OLi	-	-	-	29	58	6	90:10
10	L10	TMG-Asp	D-Pro	Aib	D-Ala	D-Ala-OLi	23	60	9	94:6
11	L11	TMG-D-Asp	D-Pro	Aib	D-Ala	D-Ala-OLi	27	57	15	34:66
12	L12	TMG-Asp	D-Pro	Aib	D-Ala-OLi	-	15	61	9	96:4
13	L13	TMG-Asp	D-Pro	Aib	Ala-OLi	-	13	61	9	96:4
14	L14	TMG-Asp	D-Pro	Aib	D-Leu-OLi	-	13	67	8	96:4
15	L15	TMG-Asp	D-Pro	Aib	D-Phe-OLi	-	15	65	9	96:4

Reported results are the average of two trials. Reaction conditions: 3 (0.2 mmol), 4-methoxyphenol (1.1 equiv), Cu(MeCN)₄BF₄ (10 mol %), peptide (20 mol %), K₃PO₄ (4.0 equiv), and MeCN (0.8 mL), 45 °C

Yield was determined using ¹H NMR by comparing to an internal NMR standard (1,4-bis(trimethylsilyl)benzene).

Enantiomeric ratios were determined using chiral HPLC analysis.

Abbreviations: TMG, tetramethylguanidine; Aib, α-aminoisobutyric acid; Cle, cycloleucine (1-aminocyclpentane-1-carboxylic acid); Acpc, 1-amino-cyclopropane-1-carboxylic acid