Relative ease of transient acyl imine formation via selenoxide, sulfoxide, and sulfone .beta. N-H elimination. A feasibility study on the preparation of novel peptide analog

Abstract

5475 morpholine for chlorine, but no elimination.Thus the sought methyl abstraction was not found for these three well-disposed electrophiles. Whether this novel reaction is viewed as a S N 2 reaction on the methyl group with an unusual carbon leaving group or as a E2 reaction with methyl abstraction, the conditions seemed strong enough to allow this reaction if it were kinetically feasible. Nor should thermodynamics have prevented reaction. For example, at 25 "C, enthalpy favors cyanide abstracting a methyl group from 1-chloropropane over cyanide abstracting hydrogen from chloroethane (AH'' = -9.4 vs -0.7 kcal/mol by heats of formation).The reason for failed methyl abstraction is open to speculation. Either a hydrogen or a methyl group on a carbon is sterically open to nucleophilic attack. Neither holds significant positive charge to attract a nucleophile.But a p hydrogen does have an advantage in being able to form a kind of hydrogen bond with the nucleophile in the transition state of a normal elimination reaction. In contrast, a methyl carbon cannot hydrogen bond and must rehybridize in its transition state. Such handicaps evidently prevent abstraction of a 0-methyl group in elimination reactions even under otherwise favorable conditions. Probably the same handicaps deter strong nucleophiles, which can abstract alcohol hydrogens, from attacking ethers. Despite many similarities between the reactivities of hydrogen and a methyl group, another significant difference has now been established. Experimental SectionDMF was purified by stirring with KOH for a few hours and then distilling from CaO onto 4A molecular sieves under aspirator vacuum. Morpholine was purified by stirring with CaS04 overnight and then fractionally distilling. Bu3N was purified by stirring with KOH overnight and then distilling at 3 mmHg. LiCl and NaCN were dried in the oven. NMR spectra were recorded on a Varian EM360A proton spectrometer and me reported in 6 units. The IR spectrum was recorded on a Perker-Elmer 1320 spectrometer. Reaction of la with LiCl.A mixture of 3.37 g (20.0 mmol) of la, 1.27 g (30.0 mmol) of LiCl, and 4.65 mL of DMF was refluxed for 4 days. NMR (DMF) 6 7.42 (br s , 5 H, Ar), 6.47 (br s, 1 H, HC=C), 2.15 (br s, 6 H, Me), very like the spectrum of authentic 2-methyl-1-phenyl-1-propene.Reaction of la with NaCN. A mixture of 3.37 g (20.0 mmol) of la, 0.98 g (20 mmol) of NaCN, and 4.65 mL of DMF was refluxed for 4 days. NMR (DMF) 6 7.39 (m, Ar), 1.47 (m, Me + CH,), consistent with 3-methyl-3-phenylbutenitrile; no vinyl protons; also peaks for starting materials.Reaction of la with Morpholine or Bu3N. A solution of 3.37 g (20.0 mmol) of la and either 3.48 g (40.0 mmol) of morpholine or 6.19 g (33.4 mmol) of Bu3N was heated at 123-129 "C for 2 days. NMR showed no reaction.Reaction of lb with LiCl or NaCN. A mixture of 2.66 g (25.0 mmol) of lb and either 2.00 g (47.2 mmol) of LiCl or 0.50 g (10 mmol) of NaCN in 11.62 mL of DMF was heated a t 200 "C in a sealed bomb for 2 days. NMR showed no reactions. Reaction of lb with Mor...

Carbon–Carbon Bond-Forming Reactions of α-Thioaryl Carbonyl Compounds for the Synthesis of Complex Heterocyclic Molecules

“…We favored the former explanation from the outset, as it would be adequately explained by preferential elimination of one diastereomer over the other, thus explaining both the low yield of sulfoxide and the high apparent diastereoselectivity of this process. Furthermore, sulfones are far less prone to elimination when compared to sulfoxides . In fact, alkyl sulfides have often served as synthetic equivalents for alkenes by virtue of the efficient oxidation/elimination sequence that can reveal the double bond …”

Synthesis of alicyclic N‐substituted 1,3‐amino alcohols via 1,3‐oxazines

“…N-Hydroxymethylbenzamide [23] (4a), N-hydroxymethylacetamide [24] (4b), the 5,6-dihydro-4H-1,3-oxazine derivatives [17] (5-7) and 6-methyl-2-phenyl-5,6-dihydro-4H-cyclohexa[e]- [1,3]oxazine [19] (8) were prepared according to literature processes.…”

Modular Construction of Protected 1,2/1,3-Diols, -Amino Alcohols, and -Diamines via Catalytic Asymmetric Dehydrative Allylation: An Application to Synthesis of Sphingosine

“…( E )-But-2-ene-1,4-diol ( 2 ) was purchased from TCI and purified by silica-gel column chromatography before use or synthesized from but-2-yne-1,4-diol according to ref . N -Boc-aminomethanol ( 4 ), N -Cbz-aminomethanol, N -Bz-aminomethanol, N -pivaloylaminomethanol, N -trifluoroacetylaminomethanol, N , N ′-bistosylaminal, ( E )-pent-2-ene-1,5-diol ( 6 ), ( E )- N -Boc-4-aminobut-2-en-1-ol ( 7 ), and ( E )- N -Boc-5-aminopent-2-en-1-ol ( 8 ) were synthesized according to the reported methods.…”

“…Abs confign was determined by comparison of the optical rotation of 5-ethenyloxazolidine-2-thione (19), which was obtained by deprotection of the 1,2-N,O module followed by thiocarbonylation. After being cooled to rt, sat aq K 2 CO 3 (3 mL) was added.…”