. Author manuscript; available in PMC: 2008 Aug 26.

Published in final edited form as: Org Lett. 2006 Oct 12;8(21):4911–4914. doi: 10.1021/ol062005s

Table 2.

Enantioselective Cross Aldol Reaction of Diethyl Formylphosphonate Hydrate (4) and Various Ketones.^a graphic file with name nihms-63822-t0008.jpg

entry	R¹	R²	product/ yield (%)^b	dr^c	ee (%)^d
1	H	H	6a/95	—	94^e
2	Me	H	6b/62^f	—	93^e
2	H	Me	6b’ /20^f	95:5^g	99^e
3	Et	H	6c/58^f	—	97^e
3	H	Et	6c’/5^f	>95:5^g	99^e
4	Cl	H	6d/65	—	90^e
5	OH	H	6e/75	—	43^h
6	OMe	H	6f/77	—	85
7	AcCH₂	H	6g/60	—	86
8	—(CH₂)₂—		6h/ 94	95:5ⁱ	>99
9	—(CH₂)₃—		6i/82	65:35^g	93(86)
10^j	—(CH₂)₃—		6i/90^k	65:35^g	96(95)
11^j	—CH₂OCH₂—		6j/85^k	70:30^g	97(99)
12^j	—CH₂SCH₂—		6k/88^k	70:30^g	93(97)^l

Unless otherwise indicated, all reactions were performed with freshly prepared diethyl formylphosphonate hydrate (4, 0.5 mmol), ketone (0.6 mL) and L-prolinamide (5 mol %) at 0 °C; the absolute configuration is tentatively assigned for 6b-k on the basis of the reaction mechanism.

Yield of isolated product after column chromatography.

Determined by ¹H NMR.

Unless otherwise noted, enantiomeric excess was determined by HPLC analyses with a Chiralpak AD-H column; values in parentheses are for the minor diastereomer.

The enantiomeric excess was determined by chiral GC analysis with a Chiraldex GTA column.

Yields of individual regioisomer as determined by ¹H NMR.

anti/syn ratio as determined by NMR.

With a Chiralcel OJ-H column.

ⁱ

syn/anti ratio as determined by NMR.

The reaction was performed with 4 (0.5 mmol), ketone (0.2 mL), CH₂Cl₂ (0.5 mL) and L-prolinamide (10mol %) at -20 °C for 24 h.

Combined yield of two inseparable diastereomers.

With a Chiralcel OD-H column.